@article{peirce-cottler_sander_fisher_deymier_ladisa_o'connell_corr_han_singh_wilson_et al._2024, title={A Systems Approach to Biomechanics, Mechanobiology, and Biotransport}, volume={146}, ISSN={["1528-8951"]}, DOI={10.1115/1.4064547}, abstractNote={Abstract}, number={4}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Peirce-Cottler, Shayn M. and Sander, Edward A. and Fisher, Matthew B. and Deymier, Alix C. and Ladisa, John F. and O'Connell, Grace and Corr, David T. and Han, Bumsoo and Singh, Anita and Wilson, Sara E. and et al.}, year={2024}, month={Apr} }
 @article{gaffney_fisher_freytes_2023, title={Tendon Extracellular Matrix Promotes Myotendinous Junction Protein Expression in Engineered Muscle Tissue under Both Static and Mechanically Stimulated Culture Conditions}, volume={2023}, ISSN={["1932-7005"]}, DOI={10.1155/2023/6658543}, abstractNote={Studying the crosstalk between the muscle and tendon tissue is an important yet understudied area in musculoskeletal research. In vitro models can help elucidate the function and repair of the myotendinous junction (MTJ) under static and dynamic culture conditions using engineered muscle tissues. The goal of this study was to culture engineered muscle tissues in a novel bioreactor in both static and mechanically stimulated cultures and evaluate the expression of MTJ-specific proteins within the muscle-tendon unit(paxillin and type XXII collagen). C2C12 myoblasts were seeded in hydrogels made from type I collagen ortendon-derived extracellular matrix (tECM) and allowed to form around movable anchors. Engineered tissues were allowed to form and stabilize for 10 days. After 10 days in the culture, stimulated cultures were cyclically stimulated for 3 hours per day for 2 and 4 weeks alongside static cultures. Strain values at the maximum displacement of the anchors averaged about 0.10, a target that has been shown to induce myogenic phenotype in C2C12s. Protein expression of paxillin after 2 weeks did not differ between hydrogel materials in static cultures but increased by 62% in tECM when mechanically stimulated. These differences continued after 4 weeks, with 31% and 57% increases in tECM tissues relative to type I collagen. Expression of type XXII collagen was similarly influenced by hydrogel material and culture conditions. Overall, this research combined a relevant microenvironment to study muscle and tendon interactions with a novel bioreactor to apply mechanical strain, an important regulator of the formation and maintenance of the native MTJ.}, journal={JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE}, author={Gaffney, Lewis S. and Fisher, Matthew B. and Freytes, Donald O.}, year={2023}, month={Aug} }
 @article{howe_dixit_saul_fisher_2022, title={A Direct Comparison of Node and Element-Based Finite Element Modeling Approaches to Study Tissue Growth}, volume={144}, ISSN={["1528-8951"]}, DOI={10.1115/1.4051661}, abstractNote={Abstract}, number={1}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Howe, Danielle and Dixit, Nikhil N. and Saul, Katherine R. and Fisher, Matthew B.}, year={2022}, month={Jan} }
 @article{howe_cone_piedrahita_spang_fisher_2022, title={Age- and Sex-Specific Joint Biomechanics in Response to Partial and Complete Anterior Cruciate Ligament Injury in the Porcine Model}, volume={57}, ISSN={["1938-162X"]}, DOI={10.4085/1062-6050-565-21}, abstractNote={
                  Context
                  Pediatric anterior cruciate ligament (ACL) injury rates are increasing and are highest in female adolescents. Complete ACL tears are typically surgically reconstructed, but few guidelines and very limited data exist regarding the need for surgical reconstruction or rehabilitation for partial ACL tears in skeletally immature patients.
               }, number={9-10}, journal={JOURNAL OF ATHLETIC TRAINING}, author={Howe, Danielle and Cone, Stephanie G. and Piedrahita, Jorge A. and Spang, Jeffrey T. and Fisher, Matthew B.}, year={2022}, month={Sep}, pages={978–989} }
 @article{lisee_bjornsen_horton_davis-wilson_blackburn_fisher_pietrosimone_2022, title={Differences in Gait Biomechanics Between Adolescents and Young Adults With Anterior Cruciate Ligament Reconstruction}, volume={57}, ISSN={["1938-162X"]}, DOI={10.4085/1062-6050-0052.22}, abstractNote={
                  Context
                  Adolescents and adults are treated similarly in rehabilitation and research despite differences in clinical recovery after anterior cruciate ligament reconstruction (ACLR). Aberrant gait is a clinical outcome associated with poor long-term health post-ACLR but has not been compared between adolescents and adults.
               }, number={9-10}, journal={JOURNAL OF ATHLETIC TRAINING}, author={Lisee, Caroline Michele and Bjornsen, Elizabeth and Horton, W. Zachary and Davis-Wilson, Hope and Blackburn, J. Troy and Fisher, Matthew B. and Pietrosimone, Brian}, year={2022}, month={Sep}, pages={921–928} }
 @article{downey_duffy_chang_fisher_moore_2022, title={Effect of epitendinous suture augmentation to a double Krackow suture pattern for canine gastrocnemius tendon repair}, volume={83}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.21.07.0100}, abstractNote={Abstract}, number={7}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Downey, Amy C. and Duffy, Daniel J. and Chang, Yi-Jen and Fisher, Matthew B. and Moore, George E.}, year={2022}, month={Jul} }
 @article{chester_lee_wagner_nordberg_fisher_brown_2022, title={Elucidating the combinatorial effect of substrate stiffness and surface viscoelasticity on cellular phenotype}, ISSN={["1552-4965"]}, DOI={10.1002/jbm.a.37367}, abstractNote={Abstract}, journal={JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A}, author={Chester, Daniel and Lee, Veronica and Wagner, Paul and Nordberg, Matthew and Fisher, Matthew B. and Brown, Ashley C.}, year={2022}, month={Feb} }
 @article{biehl_martins_davis_sze_collins_mora-navarro_fisher_freytes_2022, title={Towards a standardized multi-tissue decellularization protocol for the derivation of extracellular matrix materials}, volume={12}, ISSN={["2047-4849"]}, DOI={10.1039/d2bm01012g}, abstractNote={This study represents the first proof-of-concept standardized automated multi-tissue decellularization protocol for the derivation of ECM biomaterials.}, journal={BIOMATERIALS SCIENCE}, author={Biehl, Andreea and Martins, Ana M. Gracioso M. and Davis, Zachary G. G. and Sze, Daphne and Collins, Leonard and Mora-Navarro, Camilo and Fisher, Matthew B. B. and Freytes, Donald O. O.}, year={2022}, month={Dec} }
 @article{cone_barnes_howe_fordham_fisher_spang_2021, title={Age- and sex-specific differences in ACL and ACL bundle size during adolescent growth}, ISSN={["1554-527X"]}, DOI={10.1002/jor.25198}, abstractNote={Abstract}, journal={JOURNAL OF ORTHOPAEDIC RESEARCH}, author={Cone, Stephanie G. and Barnes, Ryan H. and Howe, Danielle and Fordham, Lynn A. and Fisher, Matthew B. and Spang, Jeffrey T.}, year={2021}, month={Nov} }
 @article{duffy_chang_fisher_moore_2021, title={Biomechanical analysis of accessory tendon graft augmentation for primary gastrocnemius tendon reconstruction in dogs}, volume={50}, ISSN={["1532-950X"]}, DOI={10.1111/vsu.13645}, abstractNote={Abstract}, number={5}, journal={VETERINARY SURGERY}, author={Duffy, Daniel J. and Chang, Yi-Jen and Fisher, Matthew B. and Moore, George E.}, year={2021}, month={Jul}, pages={1147–1156} }
 @article{duffy_chang_fisher_moore_2021, title={Biomechanical evaluation of a novel barbed suture pattern with epitendinous suture augmentation in a canine flexor tendon model}, volume={50}, ISSN={["1532-950X"]}, DOI={10.1111/vsu.13653}, abstractNote={Abstract}, number={5}, journal={VETERINARY SURGERY}, author={Duffy, Daniel J. and Chang, Yi-Jen and Fisher, Matthew B. and Moore, George E.}, year={2021}, month={Jul}, pages={1128–1136} }
 @article{chiu_duffy_chang_gaffney_fisher_2021, title={Ex vivo evaluation of novel core tenorrhaphy patterns in dogs}, ISSN={["1532-950X"]}, DOI={10.1111/vsu.13678}, abstractNote={Abstract}, journal={VETERINARY SURGERY}, author={Chiu, King Wa and Duffy, Daniel J. and Chang, Yi-Jen and Gaffney, Lewis and Fisher, Matthew B.}, year={2021}, month={Jul} }
 @article{gaffney_davis_mora-navarro_fisher_freytes_2021, title={Extracellular Matrix Hydrogels Promote Expression of Muscle-Tendon Junction Proteins}, volume={11}, ISSN={["1937-335X"]}, DOI={10.1089/ten.tea.2021.0070}, abstractNote={Muscle and tendon injuries are prevalent and range from minor sprains and strains to traumatic, debilitating injuries. However, the interactions between these tissues during injury and recovery remain unclear. Three-dimensional tissue models that incorporate both tissues and a physiologically relevant junction between muscle and tendon may help understand how the two tissues interact. Here, we use tissue specific extracellular matrix (ECM) derived from muscle and tendon to determine how cells of each tissue interact with the microenvironment of the opposite tissue, resulting in junction-specific features. The ECM materials were derived from the Achilles tendon and gastrocnemius muscle, decellularized, and processed to form tissue-specific pre-hydrogel digests. The ECM materials were unique in respect to protein composition and included many types of ECM proteins, not just collagens. After digestion and gelation, ECM hydrogels had similar complex viscosities that were less than type I collagen hydrogels at the same concentration. C2C12 myoblasts and tendon fibroblasts were cultured in tissue-specific ECM conditioned media or encapsulated in tissue-specific ECM hydrogels to determine cell-matrix interactions and the effects on a muscle-tendon junction marker, paxillin. The ECM conditioned media had only a minor effect on the upregulation of paxillin in cells cultured in monolayer. However, cells cultured within ECM hydrogels had 50-70% higher paxillin expression than cells cultured in type I collagen hydrogels. Contraction of the ECM hydrogels varied by the type of ECM used. Subsequent experiments with a varying density of type I collagen (and thus contraction) showed no correlation between paxillin expression and the amount of gel contraction, suggesting that a constituent of the ECM was the driver of paxillin expression in the ECM hydrogels. In addition, another junction marker, type XXII collagen, had similar expression patterns as paxillin, with smaller effect sizes. Using tissue-specific ECM allowed for the de-construction of the cell-matrix interactions similar to muscle-tendon junctions to study the expression of myotendinous junction-specific proteins. Impact statement The muscle-tendon junction is an important feature of muscle-tendon units; however, despite crosstalk between the two tissue types, the junction is often overlooked in current research. Deconstructing the cell-matrix interactions will provide the opportunity to study significant junction-specific features and markers that should be included in tissue models of the muscle-tendon unit, while gaining a deeper understanding of the natural junction. This research aims at informing future methods to engineer a more relevant multi-tissue platform to study the muscle-tendon unit.}, journal={TISSUE ENGINEERING PART A}, author={Gaffney, Lewis S. and Davis, Zachary G. and Mora-Navarro, Camilo and Fisher, Matthew B. and Freytes, Donald O.}, year={2021}, month={Nov} }
 @article{davis_hussain_fisher_2021, title={Processing variables of direct-write, near-field electrospinning impact size and morphology of gelatin fibers}, volume={16}, ISSN={1748-6041 1748-605X}, url={http://dx.doi.org/10.1088/1748-605X/abf88b}, DOI={10.1088/1748-605X/abf88b}, abstractNote={Abstract}, number={4}, journal={Biomedical Materials}, publisher={IOP Publishing}, author={Davis, Zachary G and Hussain, Aasim F and Fisher, Matthew B}, year={2021}, month={May}, pages={045017} }
 @article{howe_cone_piedrahita_collins_fordham_griffith_spang_fisher_2021, title={Sex-specific biomechanics and morphology of the anterior cruciate ligament during skeletal growth in a porcine model}, ISSN={["1554-527X"]}, DOI={10.1002/jor.25207}, abstractNote={Abstract}, journal={JOURNAL OF ORTHOPAEDIC RESEARCH}, author={Howe, Danielle and Cone, Stephanie G. and Piedrahita, Jorge A. and Collins, Bruce and Fordham, Lynn A. and Griffith, Emily H. and Spang, Jeffrey T. and Fisher, Matthew B.}, year={2021}, month={Nov} }
 @article{duffy_curcillo_chang_gaffney_fisher_moore_2020, title={Biomechanical evaluation of an autologous flexor digitorum lateralis graft to augment the surgical repair of gastrocnemius tendon laceration in a canine ex vivo model}, volume={49}, ISSN={["1532-950X"]}, DOI={10.1111/vsu.13453}, abstractNote={Abstract}, number={8}, journal={VETERINARY SURGERY}, author={Duffy, Daniel J. and Curcillo, Chiara P. and Chang, Yi-Jen and Gaffney, Lewis and Fisher, Matthew B. and Moore, George E.}, year={2020}, month={Dec}, pages={1545–1554} }
 @article{duffy_chang_fisher_moore_2020, title={Effect of partial vs complete circumferential epitendinous suture placement on the biomechanical properties and gap formation of canine cadaveric tendons}, volume={49}, ISSN={["1532-950X"]}, DOI={10.1111/vsu.13494}, abstractNote={Abstract}, number={8}, journal={VETERINARY SURGERY}, author={Duffy, Daniel J. and Chang, Yi-Jen and Fisher, Matthew B. and Moore, George E.}, year={2020}, month={Dec}, pages={1571–1579} }
 @article{shirwaiker_fisher_anderson_schuchard_warren_maze_grondin_ligler_pourdeyhimi_2020, title={High-Throughput Manufacture of 3D Fiber Scaffolds for Regenerative Medicine}, volume={26}, ISSN={["1937-3392"]}, DOI={10.1089/ten.tec.2020.0098}, abstractNote={Engineered scaffolds used to regenerate mammalian tissues should recapitulate the underlying fibrous architecture of native tissue to achieve comparable function. Current fibrous scaffold fabrication processes, such as electrospinning and three-dimensional (3D) printing, possess application-specific advantages, but they are limited either by achievable fiber sizes and pore resolution, processing efficiency, or architectural control in three dimensions. As such, a gap exists in efficiently producing clinically relevant, anatomically sized scaffolds comprising fibers in the 1–100 μm range that are highly organized. This study introduces a new high-throughput, additive fibrous scaffold fabrication process, designated in this study as 3D melt blowing (3DMB). The 3DMB system described in this study is modified from larger nonwovens manufacturing machinery to accommodate the lower volume, high-cost polymers used for tissue engineering and implantable biomedical devices and has a fiber collection component that uses adaptable robotics to create scaffolds with predetermined geometries. The fundamental process principles, system design, and key parameters are described, and two examples of the capabilities to create scaffolds for biomedical engineering applications are demonstrated. Impact statement Three-dimensional melt blowing (3DMB) is a new, high-throughput, additive manufacturing process to produce scaffolds composed of highly organized fibers in the anatomically relevant 1–100 μm range. Unlike conventional melt-blowing systems, the 3DMB process is configured for efficient use with the relatively expensive polymers necessary for biomedical applications, decreasing the required amounts of material for processing while achieving high throughputs compared with 3D printing or electrospinning. The 3DMB is demonstrated to make scaffolds composed of multiple fiber materials and organized into complex shapes, including those typical of human body parts.}, number={7}, journal={TISSUE ENGINEERING PART C-METHODS}, author={Shirwaiker, Rohan A. and Fisher, Matthew B. and Anderson, Bruce and Schuchard, Karl G. and Warren, Paul B. and Maze, Benoit and Grondin, Pierre and Ligler, Frances S. and Pourdeyhimi, Behnam}, year={2020}, month={Jul}, pages={364–374} }
 @article{eby_duffy_chang_gaffney_fisher_moore_2020, title={Influence of barbed epitendinous suture combined with a core locking-loop sutures to repair experimental flexor tendon lacerations}, volume={49}, ISSN={["1532-950X"]}, DOI={10.1111/vsu.13496}, abstractNote={Abstract}, number={8}, journal={VETERINARY SURGERY}, author={Eby, Adam C. and Duffy, Daniel J. and Chang, Yi-Jen and Gaffney, Lewis and Fisher, Matthew B. and Moore, George E.}, year={2020}, month={Dec}, pages={1590–1599} }
 @article{cone_lambeth_piedrahita_spang_fisher_2020, title={Joint laxity varies in response to partial and complete anterior cruciate ligament injuries throughout skeletal growth}, volume={101}, ISSN={["1873-2380"]}, DOI={10.1016/j.jbiomech.2020.109636}, abstractNote={Anterior cruciate ligament (ACL) injuries are increasingly common in the skeletally immature population. As such there is a need to increase our understanding of the biomechanical function of the joint following partial and complete ACL injury during skeletal growth. In this work, we aimed to assess changes in knee kinematics and loading of the remaining soft tissues following both partial and complete ACL injury in a porcine model. To do so, we applied anterior-posterior tibial loads and varus-valgus moments to stifle joints of female pigs ranging from early juvenile to late adolescent ages and assessed both kinematics and in-situ loads carried in the bundles of the ACL and other soft tissues including the collateral ligaments and the menisci. Partial ACL injury led to increased anterior tibial translation only in late adolescence and small increases in varus-valgus rotation at all ages. Complete ACL injury led to substantial increases in translation and rotation at all ages. At all ages, the medial collateral ligament and the medial meniscus combined to resist the majority of applied anterior tibial load following complete ACL transection. Across all ages and flexion angles, the contribution of the MCL ranged from 45 to 90% of the anterior load and the contribution of the medial meniscus ranged from 14 to 35% of the anterior load. These findings add to our current understanding of age-specific functional properties of both healthy and injured knees during skeletal growth.}, journal={JOURNAL OF BIOMECHANICS}, author={Cone, Stephanie G. and Lambeth, Emily P. and Piedrahita, Jorge A. and Spang, Jeffrey T. and Fisher, Matthew B.}, year={2020}, month={Mar} }
 @article{huebner_warren_chester_spang_brown_fisher_shirwaiker_2020, title={Mechanical properties of tissue formed in vivo are affected by 3D-bioplotted scaffold microarchitecture and correlate with ECM collagen fiber alignment}, volume={61}, ISSN={["1607-8438"]}, DOI={10.1080/03008207.2019.1624733}, abstractNote={ABSTRACT Purpose: Musculoskeletal soft tissues possess highly aligned extracellular collagenous networks that provide structure and strength. Such an organization dictates tissue-specific mechanical properties but can be difficult to replicate by engineered biological substitutes. Nanofibrous electrospun scaffolds have demonstrated the ability to control cell-secreted collagen alignment, but concerns exist regarding their scalability for larger and anatomically relevant applications. Additive manufacturing processes, such as melt extrusion-based 3D-Bioplotting, allow fabrication of structurally relevant scaffolds featuring highly controllable porous microarchitectures. Materials and Methods: In this study, we investigate the effects of 3D-bioplotted scaffold design on the compressive elastic modulus of neotissue formed in vivo in a subcutaneous rat model and its correlation with the alignment of ECM collagen fibers. Polycaprolactone scaffolds featuring either 100 or 400 µm interstrand spacing were implanted for 4 or 12 weeks, harvested, cryosectioned, and characterized using atomic-force-microscopy-based force mapping. Results: The compressive elastic modulus of the neotissue formed within the 100 µm design was significantly higher at 4 weeks (p < 0.05), but no differences were observed at 12 weeks. In general, the tissue stiffness was within the same order of magnitude and range of values measured in native musculoskeletal soft tissues including the porcine meniscus and anterior cruciate ligament. Finally, a significant positive correlation was noted between tissue stiffness and the degree of ECM collagen fiber alignment (p < 0.05) resulting from contact guidance provided by scaffold strands. Conclusion: These findings demonstrate the significant effects of 3D-bioplotted scaffold microarchitectures in the organization and sub-tissue-level mechanical properties of ECM in vivo.}, number={2}, journal={CONNECTIVE TISSUE RESEARCH}, author={Huebner, Pedro and Warren, Paul B. and Chester, Daniel and Spang, Jeffrey T. and Brown, Ashley C. and Fisher, Matthew B. and Shirwaiker, Rohan A.}, year={2020}, month={Mar}, pages={190–204} }
 @article{cone_lambeth_ru_fordham_piedrahita_spang_fisher_2019, title={Biomechanical Function and Size of the Anteromedial and Posterolateral Bundles of the ACL Change Differently with Skeletal Growth in the Pig Model}, volume={477}, ISSN={["1528-1132"]}, DOI={10.1097/CORR.0000000000000884}, abstractNote={ACL injuries are becoming increasingly common in children and adolescents, but little is known regarding age-specific ACL function in these patients. To improve our understanding of changes in musculoskeletal tissues during growth and given the limited availability of pediatric human cadaveric specimens, tissue structure and function can be assessed in large animal models, such as the pig.Using cadaveric porcine specimens ranging throughout skeletal growth, we aimed to assess age-dependent changes in (1) joint kinematics under applied AP loads and varus-valgus moments, (2) biomechanical function of the ACL under the same loads, (3) the relative biomechanical function of the anteromedial and posterolateral bundles of the ACL; and (4) size and orientation of the anteromedial and posterolateral bundles.Stifle joints (analogous to the human knee) were collected from female Yorkshire crossbreed pigs at five ages ranging from early youth to late adolescence (1.5, 3, 4.5, 6, and 18 months; n = 6 pigs per age group, 30 total), and MRIs were performed. A robotic testing system was used to determine joint kinematics (AP tibial translation and varus-valgus rotation) and in situ forces in the ACL and its bundles in response to applied anterior tibial loads and varus-valgus moments. To see if morphological changes to the ACL compared with biomechanical changes, ACL and bundle cross-sectional area, length, and orientation were calculated from MR images.Joint kinematics decreased with increasing age. Normalized AP tibial translation decreased by 44% from 1.5 months (0.34 ± 0.08) to 18 months (0.19 ± 0.02) at 60° of flexion (p < 0.001) and varus-valgus rotation decreased from 25° ± 2° at 1.5 months to 6° ± 2° at 18 months (p < 0.001). The ACL provided the majority of the resistance to anterior tibial loading at all age groups (75% to 111% of the applied anterior force; p = 0.630 between ages). Anteromedial and posterolateral bundle function in response to anterior loading and varus torque were similar in pigs of young ages. During adolescence (4.5 to 18 months), the in situ force carried by the anteromedial bundle increased relative to that carried by the posterolateral bundle, shifting from 59% ± 22% at 4.5 months to 92% ± 12% at 18 months (data for 60° of flexion, p < 0.001 between 4.5 and 18 months). The cross-sectional area of the anteromedial bundle increased by 30 mm throughout growth from 1.5 months (5 ± 2 mm) through 18 months (35 ± 8 mm; p < 0.001 between 1.5 and 18 months), while the cross-sectional area of the posterolateral bundle increased by 12 mm from 1.5 months (7 ± 2 mm) to 4.5 months (19 ± 5 mm; p = 0.004 between 1.5 and 4.5 months), with no further growth (17 ± 7 mm at 18 months; p = 0.999 between 4.5 and 18 months). However, changes in length and orientation were similar between the bundles.We showed that the stifle joint (knee equivalent) in the pig has greater translational and rotational laxity in early youth (1.5 to 3 months) compared with adolescence (4.5 to 18 months), that the ACL functions as a primary stabilizer throughout growth, and that the relative biomechanical function and size of the anteromedial and posterolateral bundles change differently with growth.Given the large effects observed here, the age- and bundle-specific function, size, and orientation of the ACL may need to be considered regarding surgical timing, graft selection, and graft placement. In addition, the findings of this study will be used to motivate pre-clinical studies on the impact of partial and complete ACL injuries during skeletal growth.}, number={9}, journal={CLINICAL ORTHOPAEDICS AND RELATED RESEARCH}, author={Cone, Stephanie G. and Lambeth, Emily P. and Ru, Hongyu and Fordham, Lynn A. and Piedrahita, Jorge A. and Spang, Jeffrey T. and Fisher, Matthew B.}, year={2019}, month={Sep}, pages={2161–2174} }
 @article{duffy_chang_gaffney_fisher_moore_2019, title={Effect of bite depth of an epitendinous suture on the biomechanical strength of repaired canine flexor tendons}, volume={80}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.80.11.1043}, abstractNote={Abstract}, number={11}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Duffy, Daniel J. and Chang, Yi-Jen and Gaffney, Lewis S. and Fisher, Matthew B. and Moore, George E.}, year={2019}, month={Nov}, pages={1043–1049} }
 @article{cone_piedrahita_spang_fisher_2019, title={In Situ Joint Stiffness Increases During Skeletal Growth but Decreases Following Partial and Complete Anterior Cruciate Ligament Injury}, volume={141}, ISSN={["1528-8951"]}, DOI={10.1115/1.4044582}, abstractNote={Abstract}, number={12}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Cone, Stephanie G. and Piedrahita, Jorge A. and Spang, Jeffrey T. and Fisher, Matthew B.}, year={2019}, month={Dec} }
 @article{hossain_detwiler_chang_caughey_fisher_nichols_merricks_raymer_whitford_bellinger_et al._2019, title={Mechanical Anisotropy Assessment in Kidney Cortex Using ARFI Peak Displacement: Preclinical Validation and Pilot In Vivo Clinical Results in Kidney Allografts}, volume={66}, ISSN={["1525-8955"]}, DOI={10.1109/TUFFC.2018.2865203}, abstractNote={The kidney is an anisotropic organ, with higher elasticity along versus across nephrons. The degree of mechanical anisotropy in the kidney may be diagnostically relevant if properly exploited; however, if improperly controlled, anisotropy may confound stiffness measurements. The purpose of this study is to demonstrate the clinical feasibility of acoustic radiation force (ARF)-induced peak displacement (PD) measures for both exploiting and obviating mechanical anisotropy in the cortex of human kidney allografts, <italic>in vivo</italic>. Validation of the imaging methods is provided by preclinical studies in pig kidneys, in which ARF-induced PD values were significantly higher (<inline-formula> <tex-math notation="LaTeX">$p < 0.01$ </tex-math></inline-formula>, Wilcoxon) when the transducer executing asymmetric ARF was oriented across versus along the nephrons. The ratio of these PD values obtained with the transducer oriented across versus along the nephrons strongly linearly correlated (<inline-formula> <tex-math notation="LaTeX">$R^{2} = 0.95$ </tex-math></inline-formula>) to the ratio of shear moduli measured by shear wave elasticity imaging. On the contrary, when a symmetric ARF was implemented, no significant difference in PD was observed (<inline-formula> <tex-math notation="LaTeX">$p > 0.01$ </tex-math></inline-formula>). Similar results were demonstrated <italic>in vivo</italic> in the kidney allografts of 14 patients. The symmetric ARF produced PD measures with no significant difference (<inline-formula> <tex-math notation="LaTeX">$p > 0.01$ </tex-math></inline-formula>) between along versus across alignments, but the asymmetric ARF yielded PD ratios that remained constant over a six-month observation period post-transplantation, consistent with stable serum creatinine level and urine protein-to-creatinine ratio in the same patient population (<inline-formula> <tex-math notation="LaTeX">$p> 0.01$ </tex-math></inline-formula>). The results of this pilot <italic>in vivo</italic> clinical study suggest the feasibility of 1) implementing symmetrical ARF to obviate mechanical anisotropy in the kidney cortex when anisotropy is a confounding factor and 2) implementing asymmetric ARF to exploit mechanical anisotropy when mechanical anisotropy is a potentially relevant biomarker.}, number={3}, journal={IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL}, author={Hossain, Md Murad and Detwiler, Randal K. and Chang, Emily H. and Caughey, Melissa C. and Fisher, Melrose W. and Nichols, Timothy C. and Merricks, Elizabeth P. and Raymer, Robin A. and Whitford, Margaret and Bellinger, Dwight A. and et al.}, year={2019}, month={Mar}, pages={551–562} }
 @article{warren_davis_fisher_2019, title={Parametric control of fiber morphology and tensile mechanics in scaffolds with high aspect ratio geometry produced via melt electrowriting for musculoskeletal soft tissue engineering}, volume={99}, ISSN={["1878-0180"]}, DOI={10.1016/j.jmbbm.2019.07.013}, abstractNote={Melt electrowriting (MEW) is an additive manufacturing technique that has the potential to create fibrous scaffolds that reproduce the scale and organization of collagen fiber networks in musculoskeletal soft tissues. For musculoskeletal soft tissue engineering, it is useful for scaffolds to have a high aspect ratio (length to width ratio of 5:1 or higher). However, the relationship between MEW process variables and the structural and mechanical properties of such scaffolds is not well understood. In addition, prior studies have cut samples from larger MEW structures, resulting in test specimens with discontinuous fibers. In this study, MEW scaffolds with low (square, 12 mm × 12 mm) and high aspect ratio (rectangular, 35 mm × 5 mm) macroscale geometries were fabricated at varying stage translation speeds or melt extrusion temperatures. Fiber morphology in both geometries and mechanical properties of the continuous rectangular structures were then quantified. Fiber diameter in both square and rectangular scaffolds generally decreased with increasing stage speed, but increased with melt temperature, though the effect of the latter was greater in square scaffolds. Interfiber spacing in both geometries was closer to the intended value as stage speed increased. Spacing became less accurate in square scaffolds with increasing melt temperature but changed little in rectangular scaffolds. Transverse fiber angle in rectangular scaffolds improved with increasing stage speed and had a median value within 1.4% of the intended angle at all temperatures. Finally, apparent tensile modulus in rectangular scaffolds decreased with increasing speed and temperature. These findings highlight the need to tailor MEW process parameters in scaffolds with high aspect ratio geometry in order to consistently generate specific structural and mechanical properties. Because of the potential to reproduce the structural anisotropy, fiber size, and mechanical properties of collagenous extracellular matrix, MEW structures are promising as musculoskeletal soft tissue scaffolds.}, journal={JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS}, author={Warren, Paul B. and Davis, Zachary G. and Fisher, Matthew B.}, year={2019}, month={Nov}, pages={153–160} }
 @misc{cone_howe_fisher_2019, title={SIZE AND SHAPE OF THE HUMAN ANTERIOR CRUCIATE LIGAMENT AND THE IMPACT OF SEX AND SKELETAL GROWTH}, volume={7}, ISSN={["2329-9185"]}, DOI={10.2106/JBJS.RVW.18.00145}, abstractNote={
            Background:
            High rates of anterior cruciate ligament (ACL) injury and surgical reconstruction in both skeletally immature and mature populations have led to many studies investigating the size and shape of the healthy ligament. The purposes of the present study were to compile existing quantitative measurements of the geometry of the ACL, its bundles, and its insertion sites and to describe effects of common covariates such as sex and age.
          }, number={6}, journal={JBJS REVIEWS}, author={Cone, Stephanie G. and Howe, Danielle and Fisher, Matthew B.}, year={2019}, month={Jun} }
 @article{cone_piercy_lambeth_ru_piedrahita_spang_fordham_fisher_2019, title={Tissue-specific changes in size and shape of the ligaments and tendons of the porcine knee during post-natal growth}, volume={14}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0219637}, abstractNote={Prior studies have analyzed growth of musculoskeletal tissues between species or across body segments; however, little research has assessed the differences in similar tissues within a single joint. Here we studied changes in the length and cross-sectional area of four ligaments and tendons, (anterior cruciate ligament, patellar tendon, medial collateral ligament, lateral collateral ligament) in the tibiofemoral joint of female Yorkshire pigs through high-field magnetic resonance imaging throughout growth. Tissue lengths increased by 4-to 5-fold from birth to late adolescence across the tissues while tissue cross-sectional area increased by 10-20-fold. The anterior cruciate ligament and lateral collateral ligament showed allometric growth favoring change in length over change in cross-sectional area while the patellar tendon and medial collateral ligament grow in an isometric manner. Additionally, changes in the length and cross-sectional area of the anterior cruciate ligament did not increase as much as in the other ligaments and tendon of interest. Overall, these findings suggest that musculoskeletal soft tissue morphometry can vary within tissues of similar structure and within a single joint during post-natal growth.}, number={10}, journal={PLOS ONE}, author={Cone, Stephanie G. and Piercy, Hope E. and Lambeth, Emily P. and Ru, Hongyu and Piedrahita, Jorge A. and Spang, Jeffrey T. and Fordham, Lynn A. and Fisher, Matthew B.}, year={2019}, month={Oct} }
 @article{pfeifer_fisher_saxena_kim_henning_steinberg_dodge_mauck_2017, title={Age-Dependent Subchondral Bone Remodeling and Cartilage Repair in a Minipig Defect Model}, volume={23}, ISSN={["1937-3392"]}, DOI={10.1089/ten.tec.2017.0109}, abstractNote={After cartilage injury and repair, the subchondral bone plate remodels. Skeletal maturity likely impacts both bone remodeling and inherent cartilage repair capacity. The objective of this study was to evaluate subchondral bone remodeling as a function of injury type, repair scenario, and skeletal maturity in a Yucatan minipig model. Cartilage defects (4 mm) were created bilaterally in the trochlear groove. Treatment conditions included a full thickness chondral defect (full chondral defect, n = 3 adult/3 juvenile), a partial thickness (∼50%) chondral defect (PCD, n = 3/3), and FCD treated with microfracture (MFX, n = 3/3). At 6 weeks postoperatively, osteochondral samples containing the lesion site were imaged by micro-computed tomography (CT) and analyzed by histology and immunohistochemistry. Via micro-CT, FCD and MFX groups showed increased bone loss in juveniles compared with adults. Quantification of histology using the ICRS II scoring system showed equal overall assessment for the FCD groups and better overall assessment in juvenile animals treated with MFX compared with adults. All FCD and MFX groups were inferior to control samples. For the PCD injury, both age groups had values close to the control values. For the FCD groups, there were greater alterations in the subchondral bone in juveniles compared with adults. Staining for collagen II showed more intense signals in juvenile FCD and MFX groups compared with adults. This large animal study of cartilage repair shows the significant impact of skeletal maturity on the propensity of subchondral bone to remodel as a result of chondral injury. This will improve selection criteria for animal models for studying cartilage injury, repair, and treatment.}, number={11}, journal={TISSUE ENGINEERING PART C-METHODS}, author={Pfeifer, Christian G. and Fisher, Matthew B. and Saxena, Vishal and Kim, Minwook and Henning, Elizabeth A. and Steinberg, David A. and Dodge, George R. and Mauck, Robert L.}, year={2017}, month={Nov}, pages={745–753} }
 @article{meloni_fisher_stoeckl_dodge_mauck_2017, title={Biphasic Finite Element Modeling Reconciles Mechanical Properties of Tissue-Engineered Cartilage Constructs Across Testing Platforms}, volume={23}, ISSN={["1937-335X"]}, DOI={10.1089/ten.tea.2016.0191}, abstractNote={Cartilage tissue engineering is emerging as a promising treatment for osteoarthritis, and the field has progressed toward utilizing large animal models for proof of concept and preclinical studies. Mechanical testing of the regenerative tissue is an essential outcome for functional evaluation. However, testing modalities and constitutive frameworks used to evaluate in vitro grown samples differ substantially from those used to evaluate in vivo derived samples. To address this, we developed finite element (FE) models (using FEBio) of unconfined compression and indentation testing, modalities commonly used for such samples. We determined the model sensitivity to tissue radius and subchondral bone modulus, as well as its ability to estimate material parameters using the built-in parameter optimization tool in FEBio. We then sequentially tested agarose gels of 4%, 6%, 8%, and 10% weight/weight using a custom indentation platform, followed by unconfined compression. Similarly, we evaluated the ability of the model to generate material parameters for living constructs by evaluating engineered cartilage. Juvenile bovine mesenchymal stem cells were seeded (2 × 107 cells/mL) in 1% weight/volume hyaluronic acid hydrogels and cultured in a chondrogenic medium for 3, 6, and 9 weeks. Samples were planed and tested sequentially in indentation and unconfined compression. The model successfully completed parameter optimization routines for each testing modality for both acellular and cell-based constructs. Traditional outcome measures and the FE-derived outcomes showed significant changes in material properties during the maturation of engineered cartilage tissue, capturing dynamic changes in functional tissue mechanics. These outcomes were significantly correlated with one another, establishing this FE modeling approach as a singular method for the evaluation of functional engineered and native tissue regeneration, both in vitro and in vivo.}, number={13-14}, journal={TISSUE ENGINEERING PART A}, author={Meloni, Gregory R. and Fisher, Matthew B. and Stoeckl, Brendan D. and Dodge, George R. and Mauck, Robert L.}, year={2017}, month={Jul}, pages={663–674} }
 @article{warren_huebner_spang_shirwaiker_fisher_2017, title={Engineering 3D-Bioplotted scaffolds to induce aligned extracellular matrix deposition for musculoskeletal soft tissue replacement}, volume={58}, ISSN={["1607-8438"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85011664862&partnerID=MN8TOARS}, DOI={10.1080/03008207.2016.1276177}, abstractNote={ABSTRACT Purpose: Tissue engineering and regenerative medicine approaches have the potential to overcome the challenges associated with current treatment strategies for meniscus injuries. 3D-Bioplotted scaffolds are promising, but have not demonstrated the ability to guide the formation of aligned collagenous matrix in vivo, which is critical for generating functional meniscus tissue. In this study, we evaluate the ability of 3D-Bioplotted scaffold designs with varying interstrand spacing to induce the deposition of aligned matrix in vivo. Materials and Methods: 3D-Bioplotted polycaprolactone scaffolds with 100, 200, or 400 μm interstrand spacing were implanted subcutaneously in a rat model for 4, 8, or 12 weeks. Scaffolds were harvested, paraffin-embedded, sectioned, and stained to visualize cell nuclei and collagen. Quantitative image analysis was used to evaluate cell density, matrix fill, and collagen fiber alignment within the scaffolds. Results: By 4 weeks, cells had infiltrated the innermost scaffold regions. Similarly, collagenous matrix filled interstrand regions nearly completely by 4 weeks. By 12 weeks, aligned collagen was present in all scaffolds. Generally, alignment along the scaffold strands increased over time for all three interstrand spacing groups. Distribution of collagen fiber alignment angles narrowed as interstrand spacing decreased. Conclusions: 3D-Bioplotted scaffolds allow for complete cell infiltration and collagenous matrix production throughout the scaffold. The ability to use interstrand spacing as a means of controlling the formation of aligned collagen in vivo was demonstrated, which helps establish a design space for scaffold-based meniscus tissue engineering.}, number={3-4}, journal={CONNECTIVE TISSUE RESEARCH}, author={Warren, Paul B. and Huebner, Pedro and Spang, Jeffrey T. and Shirwaiker, Rohan A. and Fisher, Matthew B.}, year={2017}, pages={342–354} }
 @article{gaffney_warren_wrona_fisher_freytes_2017, title={Macrophages' role in tissue disease and regeneration}, volume={62}, journal={Macrophages: origin, functions and biointervention}, author={Gaffney, L. and Warren, P. and Wrona, E. A. and Fisher, M. B. and Freytes, D. O.}, year={2017}, pages={245–271} }
 @article{cone_simpson_piedrahita_fordham_spang_fisher_2017, title={Orientation changes in the cruciate ligaments of the knee during skeletal growth: A porcine model}, volume={35}, ISSN={0736-0266}, url={http://dx.doi.org/10.1002/jor.23594}, DOI={10.1002/jor.23594}, abstractNote={ABSTRACT}, number={12}, journal={Journal of Orthopaedic Research}, publisher={Wiley}, author={Cone, Stephanie G. and Simpson, Sean G. and Piedrahita, Jorge A. and Fordham, Lynn A. and Spang, Jeffrey T. and Fisher, Matthew B.}, year={2017}, month={May}, pages={2725–2732} }
 @misc{cone_warren_fisher_2017, title={Rise of the Pigs: Utilization of the Porcine Model to Study Musculoskeletal Biomechanics and Tissue Engineering During Skeletal Growth}, volume={23}, ISSN={["1937-3392"]}, DOI={10.1089/ten.tec.2017.0227}, abstractNote={Large animal models play an essential role in the study of tissue engineering and regenerative medicine (TERM), as well as biomechanics. The porcine model has been increasingly used to study the musculoskeletal system, including specific joints, such as the knee and temporomandibular joints, and tissues, such as bone, cartilage, and ligaments. In particular, pigs have been utilized to evaluate the role of skeletal growth on the biomechanics and engineered replacements of these joints and tissues. In this review, we explore the publication history of the use of pig models in biomechanics and TERM discuss interspecies comparative studies, highlight studies on the effect of skeletal growth and other biological considerations in the porcine model, and present challenges and emerging opportunities for using this model to study functional TERM.}, number={11}, journal={TISSUE ENGINEERING PART C-METHODS}, author={Cone, Stephanie G. and Warren, Paul B. and Fisher, Matthew B.}, year={2017}, month={Nov}, pages={763–780} }
 @article{narayanan_huebner_fisher_spang_starly_shirwaiker_2016, title={3D-Bioprinting of Polylactic Acid (PLA) Nanofiber–Alginate Hydrogel Bioink Containing Human Adipose-Derived Stem Cells}, volume={2}, ISSN={2373-9878 2373-9878}, url={http://dx.doi.org/10.1021/ACSBIOMATERIALS.6B00196}, DOI={10.1021/ACSBIOMATERIALS.6B00196}, abstractNote={Bioinks play a central role in 3D-bioprinting by providing the supporting environment within which encapsulated cells can endure the stresses encountered during the digitally driven fabrication process and continue to mature, proliferate, and eventually form extracellular matrix (ECM). In order to be most effective, it is important that bioprinted constructs recapitulate the native tissue milieu as closely as possible. As such, musculoskeletal soft tissue constructs can benefit from bioinks that mimic their nanofibrous matrix constitution, which is also critical to their function. This study focuses on the development and proof-of-concept assessment of a fibrous bioink composed of alginate hydrogel, polylactic acid nanofibers, and human adipose-derived stem cells (hASC) for bioprinting such tissue constructs. First, hASC proliferation and viability were assessed in 3D-bioplotted strands over 16 days in vitro. Then, a human medial knee meniscus digitally modeled using magnetic resonance images was bioprinted and evaluated over 8 weeks in vitro. Results show that the nanofiber-reinforced bioink allowed higher levels of cell proliferation within bioprinted strands, with a peak at day 7, while still maintaining a vast majority of viable cells at day 16. The cell metabolic activity on day 7 was 28.5% higher in this bioink compared to the bioink without nanofibers. Histology of the bioprinted meniscus at both 4 and 8 weeks showed 54% and 147% higher cell density, respectively, in external versus internal regions of the construct. The presence of collagen and proteoglycans was also noted in areas surrounding the hASC, indicating ECM secretion and chondrogenic differentiation.}, number={10}, journal={ACS Biomaterials Science & Engineering}, publisher={American Chemical Society (ACS)}, author={Narayanan, Lokesh Karthik and Huebner, Pedro and Fisher, Matthew B. and Spang, Jeffrey T. and Starly, Binil and Shirwaiker, Rohan A.}, year={2016}, month={Jul}, pages={1732–1742} }
 @article{fisher_belkin_milby_henning_soeegaard_kim_pfeifer_saxena_dodge_burdick_et al._2016, title={Effects of Mesenchymal Stem Cell and Growth Factor Delivery on Cartilage Repair in a Mini-Pig Model}, volume={7}, ISSN={["1947-6043"]}, DOI={10.1177/1947603515623030}, abstractNote={Objective We have recently shown that mesenchymal stem cells (MSCs) embedded in a hyaluronic acid (HA) hydrogel and exposed to chondrogenic factors (transforming growth factor–β3 [TGF-β3]) produce a cartilage-like tissue in vitro. The current objective was to determine if these same factors could be combined immediately prior to implantation to induce a superior healing response in vivo relative to the hydrogel alone. }, number={2}, journal={CARTILAGE}, author={Fisher, Matthew B. and Belkin, Nicole S. and Milby, Andrew H. and Henning, Elizabeth A. and Soeegaard, Nicole and Kim, Minwook and Pfeifer, Christian and Saxena, Vishal and Dodge, George R. and Burdick, Jason A. and et al.}, year={2016}, month={Apr}, pages={174–184} }
 @article{nordberg_charoenpanich_vaughn_griffith_fisher_cole_spang_loboa_2016, title={Enhanced cellular infiltration of human adipose-derived stem cells in allograft menisci using a needle-punch method}, volume={11}, journal={Journal of Orthopaedic Surgery and Research}, author={Nordberg, R. C. and Charoenpanich, A. and Vaughn, C. E. and Griffith, E. H. and Fisher, M. B. and Cole, J. H. and Spang, J. T. and Loboa, E. G.}, year={2016} }
 @article{fisher_henning_soeegaard_bostrom_esterhai_mauck_2015, title={Engineering meniscus structure and function via multi-layered mesenchymal stem cell-seeded nanofibrous scaffolds}, volume={48}, ISSN={["1873-2380"]}, DOI={10.1016/j.jbiomech.2015.02.036}, abstractNote={Despite advances in tissue engineering for the knee meniscus, it remains a challenge to match the complex macroscopic and microscopic structural features of native tissue, including the circumferentially and radially aligned collagen bundles essential for mechanical function. To mimic this structural hierarchy, this study developed multi-lamellar mesenchymal stem cell (MSC)-seeded nanofibrous constructs. Bovine MSCs were seeded onto nanofibrous scaffolds comprised of poly(ε-caprolactone) with fibers aligned in a single direction (0° or 90° to the scaffold long axis) or circumferentially aligned (C). Multi-layer groups (0°/0°/0°, 90°/90°/90°, 0°/90°/0°, 90°/0°/90°, and C/C/C) were created and cultured for a total of 6 weeks under conditions favoring fibrocartilaginous tissue formation. Tensile testing showed that 0° and C single layer constructs had stiffness values several fold higher than 90° constructs. For multi-layer groups, the stiffness of 0°/0°/0° constructs was higher than all other groups, while 90°/90°/90° constructs had the lowest values. Data for collagen content showed a general positive interactive effect for multi-layers relative to single layer constructs, while a positive interaction for stiffness was found only for the C/C/C group. Collagen content and cell infiltration occurred independent of scaffold alignment, and newly formed collagenous matrix followed the scaffold fiber direction. Structural hierarchies within multi-lamellar constructs dictated biomechanical properties, and only the C/C/C constructs with non-orthogonal alignment within layers featured positive mechanical reinforcement as a consequence of the layered construction. These multi-layer constructs may serve as functional substitutes for the meniscus as well as test beds to understand the complex mechanical principles that enable meniscus function.}, number={8}, journal={JOURNAL OF BIOMECHANICS}, author={Fisher, Matthew B. and Henning, Elizabeth A. and Soeegaard, Nicole and Bostrom, Marc and Esterhai, John L. and Mauck, Robert L.}, year={2015}, month={Jun}, pages={1412–1419} }
 @article{pfeifer_fisher_carey_mauck_2015, title={Impact of guidance documents on translational large animal studies of cartilage repair}, volume={7}, ISSN={["1946-6242"]}, DOI={10.1126/scitranslmed.aac7019}, abstractNote={A systematic review of large animal cartilage repair studies demonstrates that few investigators attend to guidance documents published by regulatory agencies.}, number={310}, journal={SCIENCE TRANSLATIONAL MEDICINE}, author={Pfeifer, Christian G. and Fisher, Matthew B. and Carey, James L. and Mauck, Robert L.}, year={2015}, month={Oct} }
 @article{donahue_fisher_maher_2015, title={Meniscus mechanics and mechanobiology}, volume={48}, ISSN={["1873-2380"]}, DOI={10.1016/j.jbiomech.2015.03.020}, abstractNote={The meniscus is comprised of circumferentially aligned fibers that resist the tensile forces within the meniscus (i.e., hoop stress) that develop during loading of the knee. Although these circumferential fibers are severed by radial meniscal tears, tibial contact stresses do not increase until the tear reaches ∼90% of the meniscus width, suggesting that the severed circumferential fibers still bear load and maintain the mechanical functionality of the meniscus. Recent data demonstrates that the interfibrillar matrix can transfer strain energy to disconnected fibrils in tendon fascicles. In the meniscus, interdigitating radial tie fibers, which function to stabilize and bind the circumferential fibers together, are hypothesized to function in a similar manner by transmitting load to severed circumferential fibers near a radial tear. To test this hypothesis, we developed an engineered fibrous analog of the knee meniscus using poly(ε-caprolactone) to create aligned scaffolds with variable amounts of non-aligned elements embedded within the scaffold. We show that the tensile properties of these scaffolds are a function of the ratio of aligned to non-aligned elements, and change in a predictable fashion following a simple mixture model. When measuring the loss of mechanical function in scaffolds with a radial tear, compared to intact scaffolds, the decrease in apparent linear modulus was reduced in scaffolds containing non-aligned layers compared to purely aligned scaffolds. Increased strains in areas adjacent to the defect were also noted in composite scaffolds. These findings indicate that non-aligned (disorganized) elements interspersed within an aligned network can improve overall mechanical function by promoting strain transfer to nearby disconnected fibers. This finding supports the notion that radial tie fibers may similarly promote tear tolerance in the knee meniscus, and will direct changes in clinical practice and provide guidance for tissue engineering strategies.The meniscus is a complex fibrous tissue, whose architecture includes radial tie fibers that run perpendicular to and interdigitate with the predominant circumferential fibers. We hypothesized that these radial elements function to preserve mechanical function in the context of interruption of circumferential bundles, as would be the case in a meniscal tear. To test this hypothesis, we developed a biomaterial analog containing disorganized layers enmeshed regularly throughout an otherwise aligned network. Using this material formulation, we showed that strain transmission is improved in the vicinity of defects when disorganized fiber layers were present. This supports the idea that radial elements within the meniscus improve function near a tear, and will guide future clinical interventions and the development of engineered replacements.}, number={8}, journal={JOURNAL OF BIOMECHANICS}, author={Donahue, Tammy L. Haut and Fisher, Matthew B. and Maher, Suzanne A.}, year={2015}, month={Jun}, pages={1341–1342} }
 @article{qu_pintauro_haughan_henning_esterhai_schaer_mauck_fisher_2015, title={Repair of dense connective tissues via biomaterial-mediated matrix reprogramming of the wound interface}, volume={39}, ISSN={0142-9612}, url={http://dx.doi.org/10.1016/J.BIOMATERIALS.2014.10.067}, DOI={10.1016/J.BIOMATERIALS.2014.10.067}, abstractNote={Repair of dense connective tissues in adults is limited by their intrinsic hypocellularity and is exacerbated by a dense extracellular matrix (ECM) that impedes cellular migration to and local proliferation at the wound site. Conversely, healing in fetal tissues occurs due in part to an environment conducive to cell mobility and division. Here, we investigated whether the application of a degradative enzyme, collagenase, could reprogram the adult wound margin to a more fetal-like state, and thus abrogate the biophysical impediments that hinder migration and proliferation. We tested this concept using the knee meniscus, a commonly injured structure for which few regenerative approaches exist. To focus delivery and degradation to the wound interface, we developed a system in which collagenase was stored inside poly(ethylene oxide) (PEO) electrospun nanofibers and released upon hydration. Through a series of in vitro and in vivo studies, our findings show that partial digestion of the wound interface improves repair by creating a more compliant and porous microenvironment that expedites cell migration to and/or proliferation at the wound margin. This innovative approach of targeted manipulation of the wound interface, focused on removing the naturally occurring barriers to adult tissue repair, may find widespread application in the treatment of injuries to a variety of dense connective tissues.}, journal={Biomaterials}, publisher={Elsevier BV}, author={Qu, Feini and Pintauro, Michael P. and Haughan, Joanne E. and Henning, Elizabeth A. and Esterhai, John L. and Schaer, Thomas P. and Mauck, Robert L. and Fisher, Matthew B.}, year={2015}, month={Jan}, pages={85–94} }
 @article{farrell_fisher_huang_shin_farrell_mauck_2014, title={Functional properties of bone marrow-derived MSC-based engineered cartilage are unstable with very long-term in vitro culture}, volume={47}, ISSN={0021-9290}, url={http://dx.doi.org/10.1016/J.JBIOMECH.2013.10.030}, DOI={10.1016/J.JBIOMECH.2013.10.030}, abstractNote={The success of stem cell-based cartilage repair requires that the regenerate tissue reach a stable state. To investigate the long-term stability of tissue engineered cartilage constructs, we assessed the development of compressive mechanical properties of chondrocyte and mesenchymal stem cell (MSC)-laden three dimensional agarose constructs cultured in a well defined chondrogenic in vitro environment through 112 days. Consistent with previous reports, in the presence of TGF-β, chondrocytes outperformed MSCs through day 56, under both free swelling and dynamic culture conditions, with MSC-laden constructs reaching a plateau in mechanical properties between days 28 and 56. Extending cultures through day 112 revealed that MSCs did not simply experience a lag in chondrogenesis, but rather that construct mechanical properties never matched those of chondrocyte-laden constructs. After 56 days, MSC-laden constructs underwent a marked reversal in their growth trajectory, with significant declines in glycosaminoglycan content and mechanical properties. Quantification of viability showed marked differences in cell health between chondrocytes and MSCs throughout the culture period, with MSC-laden construct cell viability falling to very low levels at these extended time points. These results were not dependent on the material environment, as similar findings were observed in a photocrosslinkable hyaluronic acid (HA) hydrogel system that is highly supportive of MSC chondrogenesis. These data suggest that, even within a controlled in vitro environment that is conducive to chondrogenesis, there may be an innate instability in the MSC phenotype that is independent of scaffold composition, and may ultimately limit their application in functional cartilage repair.}, number={9}, journal={Journal of Biomechanics}, publisher={Elsevier BV}, author={Farrell, Megan J. and Fisher, Matthew B. and Huang, Alice H. and Shin, John I. and Farrell, Kimberly M. and Mauck, Robert L.}, year={2014}, month={Jun}, pages={2173–2182} }
 @article{fisher_henning_söegaard_dodge_steinberg_mauck_2014, title={Maximizing cartilage formation and integration via a trajectory-based tissue engineering approach}, volume={35}, ISSN={0142-9612}, url={http://dx.doi.org/10.1016/J.BIOMATERIALS.2013.11.031}, DOI={10.1016/J.BIOMATERIALS.2013.11.031}, abstractNote={Given the limitations of current surgical approaches to treat articular cartilage injuries, tissue engineering (TE) approaches have been aggressively pursued. Despite reproduction of key mechanical attributes of native tissue, the ability of TE cartilage constructs to integrate with native tissue must also be optimized for clinical success. In this paper, we propose a "trajectory-based" tissue engineering (TB-TE) approach, based on the hypothesis that time-dependent increases in construct maturation in-vitro prior to implantation (i.e. positive rates) may provide a reliable predictor of in-vivo success. As an example TE system, we utilized hyaluronic acid hydrogels laden with mesenchymal stem cells. We first modeled the maturation of these constructs in-vitro to capture time-dependent changes. We then performed a sensitivity analysis of the model to optimize the timing and amount of data collection. Finally, we showed that integration to cartilage in-vitro is not correlated to the maturation state of TE constructs, but rather their maturation rate, providing a proof-of-concept for the use of TB-TE to enhance treatment outcomes following cartilage injury. This new approach challenges the traditional TE paradigm of matching only native state parameters of maturity and emphasizes the importance of also establishing an in-vitro trajectory in constructs in order to improve the chance of in-vivo success.}, number={7}, journal={Biomaterials}, publisher={Elsevier BV}, author={Fisher, Matthew B. and Henning, Elizabeth A. and Söegaard, Nicole B. and Dodge, George R. and Steinberg, David R. and Mauck, Robert L.}, year={2014}, month={Feb}, pages={2140–2148} }
 @article{qu_lin_esterhai_fisher_mauck_2013, title={Biomaterial-mediated delivery of degradative enzymes to improve meniscus integration and repair}, volume={9}, ISSN={1742-7061}, url={http://dx.doi.org/10.1016/j.actbio.2013.01.016}, DOI={10.1016/j.actbio.2013.01.016}, abstractNote={Endogenous repair of fibrous connective tissues is limited, and there exist few successful strategies to improve healing after injury. As such, new methods that advance repair by promoting cell growth, extracellular matrix (ECM) production, and tissue integration would represent a marked clinical advance. Using the meniscus as a test platform, we sought to develop an enzyme-releasing scaffold that enhances integrative repair. We hypothesized that the high ECM density and low cellularity of native tissue present physical and biological barriers to endogenous healing, and that localized collagenase treatment might expedite cell migration to the wound edge and tissue remodeling. To test this hypothesis, we fabricated a delivery system in which collagenase was stored inside electrospun poly(ethylene oxide) (PEO) nanofibers and released upon hydration. In vitro results showed that partial digestion of the wound interface improved repair by creating a microenvironment that facilitated cell migration, proliferation and matrix deposition. Specifically, treatment with high-dose collagenase led to a 2-fold increase in cell density at the wound margin and a 2-fold increase in integrative tissue compared to untreated controls at 4 weeks (P≤0.05). Furthermore, when composite scaffolds containing both collagenase-releasing and structural fiber fractions were placed inside meniscal tears in vitro, enzyme release acted locally and resulted in a positive cellular response similar to that of global treatment with aqueous collagenase. This innovative approach to targeted enzyme delivery may aid the many patients that exhibit meniscal tears by promoting integration of the defect, thereby circumventing the pathologic consequences of partial meniscus removal, and may find widespread application in the treatment of injuries to a variety of dense connective tissues.}, number={5}, journal={Acta Biomaterialia}, publisher={Elsevier BV}, author={Qu, Feini and Lin, Jung-Ming G. and Esterhai, John L. and Fisher, Matthew B. and Mauck, Robert L.}, year={2013}, month={May}, pages={6393–6402} }
 @article{fisher_henning_söegaard_esterhai_mauck_2013, title={Organized nanofibrous scaffolds that mimic the macroscopic and microscopic architecture of the knee meniscus}, volume={9}, ISSN={1742-7061}, url={http://dx.doi.org/10.1016/j.actbio.2012.10.018}, DOI={10.1016/j.actbio.2012.10.018}, abstractNote={The menisci are crescent-shaped fibrocartilaginous tissues whose structural organization consists of dense collagen bundles that are locally aligned but show a continuous change in macroscopic directionality. This circumferential patterning is necessary for load transmission across the knee joint and is a key design parameter for tissue engineered constructs. To address this issue we developed a novel electrospinning method to produce scaffolds composed of circumferentially aligned (CircAl) nanofibers, quantified their structure and mechanics, and compared them with traditional linearly aligned (LinAl) scaffolds. Fibers were locally oriented in CircAl scaffolds, but their orientation varied considerably as a function of position (P < 0.05). LinAl fibers did not change in orientation over a similar length scale (P > 0.05). Cell seeding of CircAl scaffolds resulted in a similar cellular directionality. Mechanical analysis of CircAl scaffolds revealed significant interactions between scaffold length and region (P < 0.05), with the tensile modulus near the edge of the scaffolds decreasing with increasing scaffold length. No such differences were detected in LinAl specimens (P > 0.05). Simulation of the fiber deposition process produced “theoretical” fiber populations that matched the fiber organization and mechanical properties observed experimentally. These novel scaffolds, with spatially varying local orientations and mechanics, will enable the formation of functional anatomic meniscus constructs.}, number={1}, journal={Acta Biomaterialia}, publisher={Elsevier BV}, author={Fisher, Matthew B. and Henning, Elizabeth A. and Söegaard, Nicole and Esterhai, John L. and Mauck, Robert L.}, year={2013}, month={Jan}, pages={4496–4504} }
 @article{fisher_liang_jung_kim_zamarra_almarza_mcmahon_woo_2012, title={Potential of healing a transected anterior cruciate ligament with genetically modified extracellular matrix bioscaffolds in a goat model}, volume={20}, ISSN={0942-2056 1433-7347}, url={http://dx.doi.org/10.1007/S00167-011-1800-X}, DOI={10.1007/S00167-011-1800-X}, abstractNote={Biological augmentation to heal a torn anterior cruciate ligament (ACL) has gained significant interest. This study examined the potential advantages of using extracellular matrix (ECM) bioscaffolds from galactosyl-α(1,3)galactose deficient pigs to heal the transected ACL.In 16 skeletally mature goats, the ACL in the right hindlimb was transected and repaired. In 9 of these animals, an ECM sheet was wrapped around the injury site and with an ECM hydrogel injected into the transected site. The remaining 7 animals were treated with suture repair only. The left hindlimb served as a sham-operated control.After 12 weeks, the healing ACL in the ECM-treated group showed an abundance of continuous neo-tissue formation, while only limited tissue growth was found after suture repair only. The cross-sectional area of the ACL from the ECM-treated group was similar to sham-operated controls (n.s.) and was 4.5 times those of the suture repair group (P < 0.05). The stiffness of the femur-ACL-tibia complexes from the ECM-treated group was 2.4 times those of the suture repair group (P < 0.05). Furthermore, these values reached 48% of the sham-operated controls (53 ± 19 N/mm and 112 ± 21 N/mm, respectively, P < 0.05).The application of an ECM bioscaffold and hydrogel was found to accelerate the healing of a transected ACL following suture repair in the goat model with limited tissue hypertrophy and improvement in some of its biomechanical properties. Although more work is necessary to fully restore the function of the normal ACL, these early results offer a potential new approach to aid ACL healing.}, number={7}, journal={Knee Surgery, Sports Traumatology, Arthroscopy}, publisher={Springer Science and Business Media LLC}, author={Fisher, Matthew B. and Liang, Rui and Jung, Ho-Joong and Kim, Kwang E. and Zamarra, Giovanni and Almarza, Alejandro J. and McMahon, Patrick J. and Woo, Savio L-Y.}, year={2012}, month={Dec}, pages={1357–1365} }
 @article{liang_fisher_yang_hall_woo_2011, title={Alpha1,3-galactosyltransferase knockout does not alter the properties of porcine extracellular matrix bioscaffolds}, volume={7}, ISSN={1742-7061}, url={http://dx.doi.org/10.1016/j.actbio.2011.01.001}, DOI={10.1016/j.actbio.2011.01.001}, abstractNote={Extracellular matrix (ECM) bioscaffolds, such as porcine small intestine submucosa (SIS) and urinary bladder matrix (UBM), have been successfully used to improve soft tissue healing. Yet they contain plenty of galactose α1,3 galactose (αGal) epitopes, which cause rejection responses in pig organ transplantation to human. Recently, ECM bioscaffolds derived from genetically modified pigs that are αGal-deficient (αGal(-)) have become available. To ensure that the ECM bioscaffolds from these pigs can be used as alternatives, we examined their morphological, bioactive and biomechanical properties and compared them with those from the wild-type pigs (n=5 per group). Morphologically, the αGal(-) ECMs were found to be similar to the wild-type ECMs in gross observation and matrix appearance with hematoxylin and eosin staining. Growth factors commonly known to be present in ECM bioscaffolds, including FGF-2, TGF-β1, VEGF, IGF-1 and PDGF-BB, also showed no significant differences in terms of quantity (p>0.05) and distribution in tissue from the results of enzyme-linked immunosorbent assay, Western blot analysis and immunohistochemistry. Furthermore, a bromodeoxyuridine cell proliferation assay confirmed the bioactivity of the extracts from the αGal(-) bioscaffolds to be similar to the wild-type bioscaffolds. Under uniaxial tensile testing, no significant differences were found between the αGal(-) and wild-type bioscaffolds in terms of their viscoelastic and mechanical properties (p>0.05). These multidisciplinary results suggest that genetic modification to eliminate the αGal epitopes in the ECM bioscaffolds had not altered the properties of these ECM bioscaffolds and, as such, they should retain their performance in tissue engineering in humans.}, number={4}, journal={Acta Biomaterialia}, publisher={Elsevier BV}, author={Liang, Rui and Fisher, Matthew and Yang, Guoguang and Hall, Christine and Woo, Savio L.-Y.}, year={2011}, month={Apr}, pages={1719–1727} }
 @article{fisher_jung_mcmahon_woo_2011, title={Suture augmentation following ACL injury to restore the function of the ACL, MCL, and medial meniscus in the goat stifle joint}, volume={44}, ISSN={0021-9290}, url={http://dx.doi.org/10.1016/j.jbiomech.2011.02.141}, DOI={10.1016/j.jbiomech.2011.02.141}, abstractNote={Functional tissue engineering (FTE) approaches have shown promise in healing an injured anterior cruciate ligament (ACL) of the knee. Nevertheless, additional mechanical augmentation is needed to maintain joint stability and appropriate loading of the joint while the ACL heals. The objective of this study was to quantitatively evaluate how mechanical augmentation using sutures restores the joint kinematics as well as the distribution of loading among the ACL, medial collateral ligament, and medial meniscus (MM) in response to externally applied loads. Eight goat stifle joints were tested on a robotic/universal force–moment sensor testing system under two loading conditions: (1) a 67 N anterior tibial load (ATL) and (2) a 67 N ATL with 100 N axial compression. For each joint, four experimental conditions were tested at 30°, 60°, and 90° of flexion: the (1) intact and (2) ACL-deficient joint, as well as following (3) suture repair of the transected ACL, and (4) augmentation using sutures passed from the femur to the tibia. Under the 67 N ATL, suture augmentation could restore the anterior tibial translation (ATT) to within 3 mm of the intact joint (p>0.05), representing a 54–76% improvement over suture repair (p<0.05). With the additional axial compression, the ATT and in-situ forces of the sutures following suture augmentation remained 2–3 times closer to normal (p<0.05). Also, the in-situ forces in the MM were 58–73% lower (p<0.05). Thus, suture augmentation may be helpful in combination with FTE approaches for ACL healing by providing the needed initial joint stability while lowering the loads on the MM.}, number={8}, journal={Journal of Biomechanics}, publisher={Elsevier BV}, author={Fisher, Matthew B. and Jung, Ho-Joong and McMahon, Patrick J. and Woo, Savio L-Y.}, year={2011}, month={May}, pages={1530–1535} }
 @article{jung_vangipuram_fisher_yang_hsu_bianchi_ronholdt_woo_2011, title={The effects of multiple freeze-thaw cycles on the biomechanical properties of the human bone-patellar tendon-bone allograft}, volume={29}, ISSN={0736-0266}, url={http://dx.doi.org/10.1002/jor.21373}, DOI={10.1002/jor.21373}, abstractNote={Abstract}, number={8}, journal={Journal of Orthopaedic Research}, publisher={Wiley}, author={Jung, Ho-Joong and Vangipuram, Gautum and Fisher, Matthew B. and Yang, Guoguang and Hsu, Shanling and Bianchi, John and Ronholdt, Chad and Woo, Savio L-Y.}, year={2011}, month={Mar}, pages={1193–1198} }
 @article{zamarra_fisher_woo_cerulli_2010, title={Biomechanical evaluation of using one hamstrings tendon for ACL reconstruction: a human cadaveric study}, volume={18}, ISSN={0942-2056 1433-7347}, url={http://dx.doi.org/10.1007/S00167-009-0911-0}, DOI={10.1007/S00167-009-0911-0}, abstractNote={Harvesting both the semitendinosus and gracilis tendons for anterior cruciate ligament (ACL) reconstruction has a negative impact on muscle strength as well as knee function and stability. With a new "All-inside" technique, using only one hamstrings tendon (semitendinosus or gracilis) is possible because of a reduction in length requirements. The research question of this in vitro study was whether the use of only one hamstrings tendon (semitendinosus or gracilis) could restore knee kinematics and in situ force in the ACL to the level of an intact knee.Ten human cadaveric knees were tested in the following conditions: (1) intact, (2) ACL-deficient, and (3) ACL reconstruction with the "All-inside" technique using the (a) single semitendinosus tendon graft, or (b) single gracilis tendon graft. Using a robotic testing system, external loads, i.e. (1) an anterior tibial load of 134-N and (2) combined rotatory loads of 10-Nm valgus and 5-Nm internal tibial torques, were applied. The multiple degrees of freedom knee kinematics and the in situ forces in the ACL and ACL grafts were determined. In response to a 134-N anterior tibial load, the use of either graft could restore anterior tibial translation to within 1.3 mm of the intact knee. The in situ forces in the two grafts were not significantly different from those of the intact ACL. Under the combined rotatory loads, both grafts could restore knee kinematics as well as the in situ force in the grafts to the level of the intact ACL. The "All-inside" technique using either the semitendinosus or gracilis tendon for ACL reconstruction could satisfactorily restore time-zero knee kinematics and the in situ forces in either graft to those for the intact ACL, supporting clinical findings.}, number={1}, journal={Knee Surgery, Sports Traumatology, Arthroscopy}, publisher={Springer Science and Business Media LLC}, author={Zamarra, Giovanni and Fisher, Matthew B. and Woo, Savio L-Y. and Cerulli, Giuliano}, year={2010}, pages={11–19} }
 @article{fisher_jung_mcmahon_woo_2010, title={Evaluation of bone tunnel placement for suture augmentation of an injured anterior cruciate ligament: Effects on joint stability in a goat model}, volume={28}, ISSN={0736-0266}, url={http://dx.doi.org/10.1002/jor.21141}, DOI={10.1002/jor.21141}, abstractNote={Abstract}, number={10}, journal={Journal of Orthopaedic Research}, publisher={Wiley}, author={Fisher, Matthew B. and Jung, Ho-Joong and McMahon, Patrick J. and Woo, Savio L-Y.}, year={2010}, month={Mar}, pages={1373–1379} }
 @article{woo_liang_fisher_2009, title={Future of Orthopaedic Sports Medicine and Soft Tissue Healing: The Important Role of Engineering}, volume={2}, ISSN={1865-5025 1865-5033}, url={http://dx.doi.org/10.1007/S12195-009-0065-7}, DOI={10.1007/S12195-009-0065-7}, number={3}, journal={Cellular and Molecular Bioengineering}, publisher={Springer Science and Business Media LLC}, author={Woo, Savio L-Y. and Liang, Rui and Fisher, Matthew B.}, year={2009}, month={Jun}, pages={448–461} }
 @article{kelly_fisher_oswald_tai_mauck_ateshian_hung_2008, title={Low-Serum Media and Dynamic Deformational Loading in Tissue Engineering of Articular Cartilage}, volume={36}, ISSN={0090-6964 1573-9686}, url={http://dx.doi.org/10.1007/S10439-008-9476-1}, DOI={10.1007/S10439-008-9476-1}, abstractNote={High-serum media have been shown to produce significant improvement in the properties of tissue-engineered articular cartilage when applied in combination with dynamic deformational loading. To mitigate concerns regarding the culture variability introduced by serum, we examined the interplay between low-serum/ITS-supplemented media and dynamic deformational loading. Our results show that low serum/ITS supplementation does not support the same level of tissue formation as compared to high serum controls. In free-swelling culture, using a combination of ITS with concentrations of FBS above 2% negated the beneficial effects of ITS. Although there were beneficial effects with loading and 0.2%FBS + ITS, these constructs significantly underperformed relative to 20%FBS constructs. At 2%FBS + ITS, the free-swelling construct stiffness and composition approached or exceeded that of 20%FBS constructs. With dynamic loading, the properties of 2%FBS + ITS constructs were significantly lower than free-swelling controls and 20%FBS constructs by day 42. By priming the chondrocytes in 20%FBS prior to exposure to low-serum/ITS media, we observed that low-serum/ITS media produced significant enhancement in tissue properties compared to constructs grown continuously in 20%FBS.}, number={5}, journal={Annals of Biomedical Engineering}, publisher={Springer Science and Business Media LLC}, author={Kelly, Terri-Ann N. and Fisher, Matthew B. and Oswald, Elizabeth S. and Tai, Timon and Mauck, Robert L. and Ateshian, Gerard A. and Hung, Clark T.}, year={2008}, month={Feb}, pages={769–779} }