Tissue Engineering Part A最新文献

{"title":"A Hybrid Scaffold Induces Chondrogenic Differentiation and Enhances <i>In Vivo</i> Cartilage Regeneration.","authors":"Jiaming Zhao, Zexing Yan, Yufei Ding, Yike Dai, Ziyang Feng, Zhiyao Li, Lifeng Ma, Naicheng Diao, Ai Guo, Heyong Yin","doi":"10.1089/ten.TEA.2023.0344","DOIUrl":"10.1089/ten.TEA.2023.0344","url":null,"abstract":"<p><p>Extensively researched tissue engineering strategies involve incorporating cells into suitable biomaterials, offering promising alternatives to boost tissue repair. In this study, a hybrid scaffold, Gel-DCM, which integrates a photoreactive gelatin-hyaluronic acid hydrogel (Gel) with an oriented porous decellularized cartilage matrix (DCM), was designed to facilitate chondrogenic differentiation and cartilage repair. The Gel-DCM exhibited excellent biocompatibility <i>in vitro</i>, promoting favorable survival and growth of human adipose-derived stem cells (hADSCs) and articular chondrocytes (hACs). Gene expression analysis indicated that the hACs expanded within the Gel-DCM exhibited enhanced chondrogenic phenotype. In addition, Gel-DCM promoted chondrogenesis of hADSCs without the supplementation of exogenous growth factors. Following this, <i>in vivo</i> experiments were conducted where empty Gel-DCM or Gel-DCM loaded with hACs/hADSCs were used and implanted to repair osteochondral defects in a rat model. In the control group, no implants were delivered to the injury site. Interestingly, macroscopic, histological, and microcomputed tomography scanning results revealed superior cartilage restoration and subchondral bone reconstruction in the empty Gel-DCM group compared with the control group. Moreover, both hACs-loaded and hADSCs-loaded Gel-DCM implants exhibited superior repair of hyaline cartilage and successful reconstruction of subchondral bone, whereas defects in the control groups were predominantly filled with fibrous tissue. These observations suggest that the Gel-DCM can provide an appropriate three-dimensional chondrogenic microenvironment, and its combination with reparative cell sources, ACs or ADSCs, holds great potential for facilitating cartilage regeneration.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"219-233"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140337849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In Vivo</i> Engineering and Transplantation of Axially Vascularized and Epithelialized Flaps in Rats.","authors":"Simon Andreas Mayer, Benjamin Thomas, Miriam Heuer, Jan C Brune, Volker Eras, Kilian Schuster, Leonard Knoedler, Rebecca Luisa Schaefer, Wilko Thiele, Jonathan P Sleeman, Arno Dimmler, Patrick Heimel, Ulrich Kneser, Amir K Bigdeli, Florian Falkner","doi":"10.1089/ten.TEA.2024.0037","DOIUrl":"10.1089/ten.TEA.2024.0037","url":null,"abstract":"<p><p>The arteriovenous loop (AVL) model allows the <i>in vivo</i> engineering of axially vascularized flaps, the so-called AVL flaps. Although AVL flaps can be transplanted microsurgically to cover tissue defects, they lack an epithelial layer on the surface. Therefore, the objective of this study was to engineer axially vascularized AVL flaps with an accompanying epithelial layer for local defect reconstruction. In this study, AVLs were established in 20 male Lewis rats. Minimally invasive injection of keratinocytes onto the surface of the AVL flaps was performed on postoperative day (POD) 21. AVL flaps were explanted from 12 rats on POD 24 or POD 30, then the epithelium formed by the keratinocytes on the surface of the flaps was evaluated using immunofluorescence staining. In six other rats, the AVL flap was locally transposed to cover a critical defect in the rats' leg on POD 30 and explanted for analysis on POD 40. In two control rats, sodium chloride was applied instead of keratinocytes. These control flaps were also transplanted on POD 30 and explanted on POD 40. Our results revealed that 3 days after keratinocyte application, a loose single-layered epithelium was observed histologically on the AVL flaps surface, whereas after 9 days, a multilayered and structured epithelium had grown. The epithelium on the transplanted AVL flaps showed its physiological differentiation when being exposed to an air-liquid interface. Histologically, a layered epithelium identical to the rats' regular skin was formed. In the sodium chloride control group, no epithelium had been grown. This study clearly demonstrates that axially vascularized AVL flaps can be processed in the subcutaneous chamber by minimally invasive injection of keratinocytes. Thus, AVL flaps with an intact epithelial layer were engineered and could be successfully transplanted for local defect coverage in a small animal model.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"234-243"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quality Assessment by Bile Composition in Normothermic Machine Perfusion of Rat Livers.","authors":"Vanessa Muth, Felix Strobl, Julian Michelotto, Linda Gilles, Jennifer A Kirwan, Alina Eisenberger, Jeremy Marchand, Nathalie N Roschke, Simon Moosburner, Johann Pratschke, Igor M Sauer, Nathanael Raschzok, Joseph M G V Gassner","doi":"10.1089/ten.TEA.2024.0048","DOIUrl":"10.1089/ten.TEA.2024.0048","url":null,"abstract":"<p><p><b><i>Background:</i></b> The persistent challenge of organ scarcity in liver transplantation leads to an escalating dependence on organs obtained from extended criteria donors (ECD). Normothermic machine perfusion (NMP) is used for improved preservation. Due to the mimicked <i>in vivo</i> conditions during normothermic machine perfusion, the liver is metabolically active, which allows quality assessment during perfusion. Bile seems to be of rising interest in clinical studies, as it is easily collectible for analysis. As there are currently no data on biliary bile acids during NMP, the primary objective of this study was to use our experimental rodent NMP model to assess changes in bile composition through organ damage during perfusion to inform clinical evaluation of donor organs during NMP. <b><i>Methods:</i></b> Thirty livers from male Sprague-Dawley rats in five groups underwent 6 h of NMP using either erythrocyte-supplemented DMEM or Steen solution, with or without 30 min of warm ischemia time (WIT). We conducted regular measurements of AST, ALT, LDH, and urea levels in the perfusate at 3-hour intervals. Bile samples were analyzed for biliary pH, LDH, and gamma glutamyltransferase, as well as biliary bile acids via mass spectrometry and UHPLC. <b><i>Results:</i></b> Compared with regular livers, liver injury parameters were significantly higher in our donation after circulatory death (DCD) model. Bile production was significantly reduced in livers exposed to WIT, and the bile showed a significantly more alkaline pH. This correlated with the concentration of total bile acids, which was significantly higher in livers experiencing WIT. However, regular livers produced a higher total amount of biliary bile acids during perfusion. Taurocholic acid and its metabolites were most prominent. Secondary bile acids were significantly reduced during perfusion due to the missing enterohepatic circulation. <b><i>Conclusions:</i></b> WIT-induced liver injury affects bile composition within our small-animal NMP model. We hypothesize this phenomenon to be attributed to the energy-driven nature of bile secretion, potentially explaining why DCD livers produce less, yet more concentrated, bile. Our results may inform clinical studies, in which biliary bile acids might have a potential as a quantifiable viability marker in human NMP liver transplantation studies.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"244-254"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tuning the Response of Synthetic Mechanogenetic Gene Circuits Using Mutations in TRPV4.","authors":"Yu Seon Kim, Nancy Steward, Autumn Kim, Isabella Fehle, Farshid Guilak","doi":"10.1089/ten.TEA.2024.0163","DOIUrl":"10.1089/ten.TEA.2024.0163","url":null,"abstract":"<p><p>Conventional gene therapy approaches for drug delivery generally rely on constitutive expression of the transgene and thus lack precise control over the timing and magnitude of delivery. Synthetic gene circuits with promoters that are responsive to user-defined stimuli can provide a molecular switch that can be utilized by cells to control drug production. Our laboratory has previously developed a mechanogenetic gene circuit that can deliver biological drugs, such as interleukin-1 receptor antagonist (IL-1Ra), on-demand through the activation of Transient receptor potential family, vanilloid 4 (TRPV4), a mechanosensory ion channel that has been shown to be activated transiently in response to physical stimuli such as physiological mechanical loading or hypo-osmotic stimuli. The goal of this study was to use mutations in TRPV4 to further tune the response of this mechanogenetic gene circuit. Human iPSC-derived chondrocytes harboring targeted gain-of-function mutations of TRPV4 were chondrogenically differentiated. Both mutants-V620I and T89I-showed greater total IL-1Ra production compared with wild type following TRPV4 agonist treatment, as well as mechanical or osmotic loading, but with altered temporal dynamics. Gene circuit output was dependent on the degree of TRPV4 activation secondary to GSK101 concentration or strain magnitude during loading. V620I constructs secreted more IL-1Ra compared with T89I across all experimental conditions, indicating that two mutations that cause similar functional changes to TRPV4 can result in distinct circuit activation profiles that differ from wild-type cells. In summary, we successfully demonstrate proof-of-concept that point mutations in TRPV4 that alter channel function can be used to tune the therapeutic output of mechanogenetic gene circuits.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"174-183"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decellularized Extracellular Matrix Improves Mesenchymal Stromal Cell Spheroid Response to Chondrogenic Stimuli.","authors":"David H Ramos-Rodriguez, Shierly W Fok, Connor J Dorais, Andrea C Filler, Mason Caserta, J Kent Leach","doi":"10.1089/ten.tea.2024.0267","DOIUrl":"10.1089/ten.tea.2024.0267","url":null,"abstract":"<p><p>Cartilage regeneration is hindered due to the low proliferative capacity of chondrocytes and the avascular nature of cartilaginous tissue. Mesenchymal stromal cells (MSCs) are widely studied for cartilage tissue engineering, and the aggregation of MSCs into high-density cell spheroids facilitates chondrogenic differentiation due to increased cell-cell contact. Despite the promise of MSCs, the field would benefit from improved strategies to regulate the chondrogenic potential of MSCs differentiated from induced pluripotent stem cells (iPSCs), which are advantageous for their capacity to yield large numbers of required cells. We previously demonstrated the ability of MSC-secreted extracellular matrix (ECM) to promote MSC chondrogenic differentiation, but the combinatorial effect of iPSC-derived MSC (iMSC) spheroids, iMSC-derived decellularized ECM (idECM), and other stimuli (e.g., oxygen tension and transforming growth factor [TGF]-β) on chondrogenic potential has not been described. Similar to MSCs, iMSCs secreted a collagen-rich ECM. When incorporated into spheroids, idECM increased spheroid diameter and promoted chondrogenic differentiation. The combination of idECM loading, chondrogenic media, and hypoxia enhanced glycosaminoglycan (GAG) content 1.6-fold (40.9 ± 4.6 ng vs. 25.6 ± 3.3 ng, <i>p</i> < 0.05) in iMSC spheroids. Compared with active TGF-β1, the presentation of latent TGF-β1 resulted in greater GAG content (26.6 ± 1.8 ng vs. 41.9 ± 4.3 ng, <i>p</i> < 0.01). Finally, we demonstrated the capacity of individual spheroids to self-assemble into larger constructs and undergo both chondrogenic and hypertrophic differentiation when maintained in lineage-inducing media. These results highlight the potential of idECM to enhance the efficacy of chondrogenic stimuli for improved cartilage regeneration using human MSCs and iMSCs.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"139-151"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved Mesenchymal Stem Cell Viability in High-Stiffness, Translational Cartilage Matrix Hydrogels.","authors":"Emi A Kiyotake, Claudia Iribagiza, Krisha Pramod, Tingting Gu, Jakob M Townsend, Michael S Detamore","doi":"10.1089/ten.tea.2024.0331","DOIUrl":"10.1089/ten.tea.2024.0331","url":null,"abstract":"<p><p>Scaffolds made from cartilage extracellular matrix are promising materials for articular cartilage repair, attributed to their intrinsic bioactivity that may promote chondrogenesis. While several cartilage matrix-based scaffolds have supported chondrogenesis <i>in vitro</i> and/or <i>in vivo</i>, it remains a challenge to balance the biological response (e.g., chondroinductivity) with structural (e.g., robust mechanical performance, >1 MPa in compressive stiffness) and translational (e.g., ease of surgical implantation) considerations. Few studies have evaluated encapsulated cell viability within high-stiffness (>1 MPa) hydrogels. We previously fabricated one formulation of a high-stiffness (>3 MPa) pentenoate-functionalized, solubilized, devitalized cartilage (PSDVC) hydrogel that possessed an injectable, paste-like precursor for easy surgical application. In the current study, the characterization of the PSDVC material was expanded by varying the degree of functionalization (i.e., 0.45-1.09 mmol/g) and amount of crosslinker, dithiothreitol (DTT), to improve the reproducibility of the high compressive moduli and evaluate the viability of encapsulated human bone marrow-derived mesenchymal stem cells (hBMSCs) in high-stiffness cartilage matrix hydrogels. Prior to crosslinking, specific formulations functionalized with 0.80 mmol/g or less of pentenoate groups retained a paste-like precursor rheology. After crosslinking, these formulations produced hydrogels with greater than 1 MPa compressive stiffness. However, hBMSCs encapsulated in PSDVC hydrogels with lower functionalization (i.e., 0.57 mmol/g, no crosslinker) had a higher stiffness (i.e., 1.4 MPa) but the lowest viability of encapsulated hBMSCs (i.e., 5%). The middle PSDVC functionalization (i.e., 0.70 mmol/g) with DTT (i.e., 0.50 mmol thiols/g) demonstrated high cell viability (77%), high mechanical performance (1.65 MPa, 31% failure strain), and translational features (i.e., paste-like precursor, 1.5 min crosslinking time). For future evaluations of PSDVC hydrogels in cartilage repair, a middle functionalization (i.e., 0.70-0.80 mmol/g) with the addition of a crosslinker (i.e., 0.50 mmol thiols/g) had a desirable balance of high mechanical performance (i.e., >1 MPa compressive stiffness), high viability, and paste-like precursor for surgical translation.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"152-163"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interspecies Comparison of Multilayer Mechanical Properties of Synovium Using Atomic Force Microscopy.","authors":"Shamimur R Akanda, Christopher Walter, Alexandra L Davis, Liufang Jing, Amit Pathak, Lori A Setton","doi":"10.1089/ten.tea.2024.0221","DOIUrl":"10.1089/ten.tea.2024.0221","url":null,"abstract":"<p><p>The synovium is a loose connective tissue that separates the intra-articular (IA) joint compartments of all diarthrodial joints from the systemic circulation. It can be divided into two layers: the intima, a thin and cell-dense layer atop a more heterogeneous subintima, composed of collagen and various cell types. The subintima contains penetrating capillaries and lymphatic vessels that rapidly clear injected drugs from the joint space which may vary not only with drug size and charge but also with the microstructure and composition of the intima and subintima of the synovium. Prior work has measured the mechanical properties and solute diffusivities in the synovium of porcine, bovine, and human joints. Here, we measured the Young's moduli of synovium from smaller joints of the rat knee, as well as pig and human, using atomic force microscopy (AFM). The format for AFM enabled testing of intima and subintimal regions of synovium in all three species. The Young's moduli of the subintimal regions were similar across all three species (1-1.5 kPa). Furthermore, there was little evidence of differences in Young's moduli between synovium from the intima and subintima in each species. A general similarity of data from AFM testing with moduli measured with bulk testing of pig and human synovium suggests that AFM can be useful to measure the mechanical properties of smaller joint synovium and spatial variations in stiffness with depth. Enzymatic digestion of synovium tissue from the pig was also performed with findings of lower moduli values following treatment with chondroitinase ABC but not collagenase. Although the molecular composition of the synovium is not yet fully characterized and may vary across species, these findings suggest that noncollagenous species contribute to AFM-measured properties in synovium. These are some of the first data to measure mechanical properties in small joint synovium and will be useful in models studying IA drug clearances in joints with pathology and following treatment.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":"31 3-4","pages":"100-107"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Prof. Kyriacos A. Athanasiou Special Issue.","authors":"Farshid Guilak, Michael Detamore, Gabriela Espinosa, Jerry Hu","doi":"10.1089/ten.tea.2025.0011","DOIUrl":"10.1089/ten.tea.2025.0011","url":null,"abstract":"","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"83-86"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differentiated and Untreated Juvenile Chondrocyte Sheets Regenerate Cartilage Similarly <i>In Vivo</i>.","authors":"Nicolás F Metzler, Makoto Kondo, Keisuke Matsukura, Adam J Ford, David W Grainger, Teruo Okano","doi":"10.1089/ten.tea.2024.0208","DOIUrl":"10.1089/ten.tea.2024.0208","url":null,"abstract":"<p><p>Osteoarthritis, a degenerative disease of articular cartilage and the leading cause of disability, is preceded by acute cartilage injury in a significant proportion of cases. Current auto- and allograft interventions are limited by supply and variability in therapeutic efficacy, prompting interest in tissue engineering solutions. Cell sheet tissue engineering, a scaffold-free regenerative technique, has shown promise in preclinical and clinical trials across various cell types and diseases. Polydactyly-derived juvenile cartilage-derived chondrocyte (JCC) sheets from juvenile patients are a potent cell source for developing allogeneic therapies. JCC sheets have proven safe and effective in animal models and as an add-on therapy in a recent clinical cartilage repair study. However, JCC <i>ex vivo</i> expansion leads to de-differentiation, contributing to long healing times. This study hypothesized that <i>in vitro</i> differentiation of JCC sheets into hyaline-like cartilage constructs could accelerate cartilage regeneration without compromising implant integration. To this end, sheet integration, maturation, and healing of conventionally prepared vs. differentiated JCC sheets were compared in an established nude rat focal chondral defect model. Differentiated JCC sheets exhibit mature cartilage phenotypes prior to transplant. Both conventional and differentiated JCC sheets are reliably transplanted without additional fixation. Histological evaluation reveals that both transplant groups produced equivalent neocartilage regeneration, filling defects with mature hyaline cartilage at 2- and 4-weeks post-transplant. Notably, differentiated JCC sheets respond to <i>in vivo</i> signals, undergoing matrix remodeling and integration with adjacent and subchondral tissue. Given equivalent healing outcomes, the future utility of <i>in vitro</i> JCC sheet predifferentiation from other JCC donors with different healing capacities should be balanced against their increased culture costs over conventional sheets.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"184-194"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Release of TSG-6 from Heparin Hydrogels on Supraspinatus Muscle Regeneration.","authors":"Joseph J Pearson, Jiahui Mao, Johnna S Temenoff","doi":"10.1089/ten.tea.2024.0241","DOIUrl":"10.1089/ten.tea.2024.0241","url":null,"abstract":"<p><p>Muscle degeneration after rotator cuff tendon tear is a significant clinical problem. In these experiments, we developed a poly(ethylene glycol)-based injectable granular hydrogel containing two heparin derivatives (fully sulfated [Hep] and fully desulfated [Hep-]) as well as a matrix metalloproteinase-sensitive peptide to promote sustained release of tumor necrosis factor-stimulated gene 6 (TSG-6) over 14+ days <i>in vivo</i> in a rat model of rotator cuff muscle injury. The hydrogel formulations demonstrated similar release profiles <i>in vivo</i>, thus facilitating comparisons between delivery from heparin derivatives on the level of tissue repair in two different areas of muscle (near the myotendious junction [MTJ] and in the muscle belly [MB]) that have been shown previously to have differing responses to rotator cuff tendon injury. We hypothesized that sustained delivery of TSG-6 would enhance the anti-inflammatory response following rotator cuff injury through macrophage polarization and that release from Hep would potentiate this effect throughout the muscle. Inflammatory/immune cells, satellite cells, and fibroadipogenic progenitor cells were analyzed by flow cytometry 3 and 7 days after injury and hydrogel injection, while metrics of muscle healing were examined via immunohistochemistry up to day 14. Results showed controlled delivery of TSG-6 from Hep caused heightened macrophage response (day 7 macrophages, 4.00 ± 1.85% single cells, M2a, 3.27 ± 1.95% single cells) and increased markers of early muscle regeneration (embryonic heavy chain staining) by day 7, particularly in the MTJ region of the muscle. This work provides a novel strategy for localized, controlled delivery of TSG-6 to enhance muscle healing after rotator cuff tear.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"195-207"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}