@article{gracioso martins_biehl_sze_freytes_2022, title={Bioreactors for Vocal Fold Tissue Engineering}, volume={28}, ISSN={["1937-3376"]}, DOI={10.1089/ten.teb.2020.0285}, abstractNote={It is estimated that almost one-third of the United States population will be affected by a vocal fold (VF) disorder during their lifespan. Promising therapies to treat VF injury and scarring are mostly centered on VF tissue engineering strategies such as the injection of engineered biomaterials and cell therapy. VF tissue engineering, however, is a challenging field as the biomechanical properties, structure, and composition of the VF tissue change upon exposure to mechanical stimulation. As a result, the development of long-term VF treatment strategies relies on the characterization of engineered tissues under a controlled mechanical environment. In this review, we highlight the importance of bioreactors as a powerful tool for VF tissue engineering with a focus on the current state of the art of bioreactors designed to mimic phonation in vitro. We discuss the influence of the phonatory environment on the development, function, injury, and healing of the VF tissue and its importance for the development of efficient therapeutic strategies. A concise and comprehensive overview of bioreactor designs, principles, operating parameters, and scalability are presented. An in-depth analysis of VF bioreactor data to date reveals that mechanical stimulation significantly influences cell viability and the expression of proinflammatory and profibrotic genes in vitro. Although the precision and accuracy of bioreactors contribute to generating reliable results, diverse gene expression profiles across the literature suggest that future efforts should focus on the standardization of bioreactor parameters to enable direct comparisons between studies. Impact statement We present a comprehensive review of bioreactors for vocal fold (VF) tissue engineering with a focus on the influence of the phonatory environment on the development, function, injury, and healing of the VFs and the importance of mimicking phonation on engineered VF tissues in vitro. Furthermore, we put forward a strong argument for the continued development of bioreactors in this area with an emphasis on the standardization of bioreactor designs, principles, operating parameters, and oscillatory regimes to enable comparisons between studies.}, number={1}, journal={TISSUE ENGINEERING PART B-REVIEWS}, author={Gracioso Martins, Ana M. and Biehl, Andreea and Sze, Daphne and Freytes, Donald O.}, year={2022}, month={Feb}, pages={182–205} }
 @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={The goal of tissue decellularization is to efficiently remove unwanted cellular components, such as DNA and cellular debris, while retaining the complex structural and molecular milieu within the extracellular matrix (ECM). Decellularization protocols to date are centered on customized tissue-specific and lab-specific protocols that involve consecutive manual steps which results in variable and protocol-specific ECM material. The differences that result from the inconsistent protocols between decellularized ECMs affect consistency across batches, limit comparisons between results obtained from different laboratories, and could limit the transferability of the material for consistent laboratory or clinical use. The present study is the first proof-of-concept towards the development of a standardized protocol that can be used to derive multiple ECM biomaterials (powders and hydrogels) via a previously established automated system. The automated decellularization method developed by our group was used due to its short decellularization time (4 hours) and its ability to reduce batch-to-batch variability. The ECM obtained using this first iteration of a unified protocol was able to produce ECM hydrogels from skin, lung, muscle, tendons, cartilage, and laryngeal tissues. All hydrogels formed in this study were cytocompatible and showed gelation and rheological properties consistent with previous ECM hydrogels. The ECMs also showed unique proteomic composition. The present study represents the first step towards developing standardized protocols that can be used on multiple tissues in a fast, scalable, and reproducible manner.}, 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{mora-navarro_ozpinar_sze_martin_freytes_2021, title={Transcriptome-targeted analysis of human peripheral blood-derived macrophages when cultured on biomaterial meshes}, volume={16}, ISSN={["1748-605X"]}, url={http://dx.doi.org/10.1088/1748-605x/abdbdb}, DOI={10.1088/1748-605X/abdbdb}, abstractNote={Surgical meshes are commonly used to repair defects and support soft tissues. Macrophages (Mφs) are critical cells in the wound healing process and are involved in the host response upon foreign biomaterials. There are various commercially available permanent and absorbable meshes used by surgeons for surgical interventions. Polypropylene (PP) meshes represent a permanent biomaterial that can elicit both inflammatory and anti-inflammatory responses. In contrast, poly-4-hydroxybutyrate (P4HB) based meshes are absorbable and linked to positive clinical outcomes but have a poorly characterized immune response. This study evaluated the in vitro targeted transcriptomic response of human Mφs seeded for 48 h on PP and P4HB surgical meshes. The in vitro measured response from human Mφs cultured on P4HB exhibited inflammatory and anti-inflammatory gene expression profiles typically associated with wound healing, which aligns with in vivo animal studies from literature. The work herein provides in vitro evidence for the early transcriptomic targeted signature of human Mφs upon two commonly used surgical meshes. The findings suggest a transition from an inflammatory to a non-inflammatory phenotype by P4HB as well as an upregulation of genes annotated under the pathogen response pathway.}, number={2}, journal={BIOMEDICAL MATERIALS}, publisher={IOP Publishing}, author={Mora-Navarro, Camilo and Ozpinar, Emily W. and Sze, Daphne and Martin, David P. and Freytes, Donald O.}, year={2021}, month={Mar} }