Tissue Engineering Part A最新文献

{"title":"Perspectives on Recent Developments and Directions in Tissue Engineering and Regenerative Medicine.","authors":"Nasim Annabi, Elizabeth Cosgriff-Hernandez, Anthony S Weiss","doi":"10.1089/ten.tea.2024.0313","DOIUrl":"https://doi.org/10.1089/ten.tea.2024.0313","url":null,"abstract":"<p><p>This perspective article draws on lessons learned at the 7th TERMIS World Congress held in Seattle, Washington in June 2024. This gathering of prominent researchers and translational scientists in tissue engineering and regenerative medicine (TERM) from around the world provided a forum to consider the impact of tissue engineering and its future directions. New frontiers are considered in the context of global challenges, including clinical translation and recent advances in pediatric tissue engineering, supercritical fluid technology for scaffold fabrication and sterilization, and learning from successful failures in tissue engineering and regenerative medicine. Bench-to-bedside translational strategies, inclusive research strategies, regulatory hurdles, and ethics linked to navigating responsibilities and innovations, are identified as important drivers in the field.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689754","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":"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":"https://doi.org/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":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":"https://doi.org/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":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","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":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","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}

{"title":"Applications of Regenerative Tissue-Engineered Scaffolds for Treatment of Spinal Cord Injury.","authors":"Katherine J Bradshaw, Nic D Leipzig","doi":"10.1089/ten.tea.2024.0194","DOIUrl":"https://doi.org/10.1089/ten.tea.2024.0194","url":null,"abstract":"<p><p>Tissue engineering provides a path forward for emerging personalized medicine therapies as well as the ability to bring about cures for diseases or chronic injuries. Traumatic spinal cord injuries (SCIs) are an example of a chronic injury in which no cure or complete functional recovery treatment has been developed. In part, this has been due to the complex and interconnected nature of the central nervous system (CNS), the cellular makeup, its extracellular matrix (ECM), and the injury site pathophysiology. One way to combat the complex nature of an SCI has been to create functional tissue-engineered scaffolds that replace or replenish the aspects of the CNS and tissue/ECM that are damaged following the immediate injury and subsequent immune response. This can be achieved by employing the tissue-engineering triad consisting of cells, biomaterial(s), and environmental factors. Stem cells, with their innate ability to proliferate and differentiate, are a common choice for cellular therapies. Natural or synthetic biomaterials that have tunable characteristics are normally used as the scaffold base. Environmental factors can range from drugs to growth factors (GFs) or proteins, depending on if the idea would be to stimulate exogeneous or endogenous cell populations or just simply retain cells on the scaffold for effective transplantation. For functional regeneration and integration for SCI, the scaffold must promote neuroprotection and neuroplasticity. Tissue-engineering strategies have shown benefits including neuronal differentiation, axonal regeneration, axonal outgrowth, integration into the native spinal cord, and partial functional recovery. Overall, this review focuses on the background that causes SCI to be so difficult to treat, the individual components of the tissue-engineering triad, and how combinatorial scaffolds can be beneficial toward the prospects of future SCI recovery.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649570","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":"The Effects of Negative Pressure Therapy on Hair Growth of Mouse Models.","authors":"Chun-Yu Cheng, Ming-Huei Cheng, Chin-Yu Yang, Cheng-Han Wang, Joshua Lim, Wei Huang, Chih-Hsin Lin","doi":"10.1089/ten.TEA.2024.0056","DOIUrl":"10.1089/ten.TEA.2024.0056","url":null,"abstract":"<p><p>Negative pressure therapy (NPT) has been shown to facilitate wound healing and promote hair growth in a porcine model. However, there is a paucity of research on the impact of negative pressure on hair growth in murine models. Despite the ability of nude mice to develop hair follicles, the hair they produce is often flawed towing to genetically induced keratin disorders, rendering them a pertinent animal model for assessing hair regeneration. Therefore, this study aims to investigate the effects of negative pressure on hair follicle growth in a nude mouse model. To achieve this, a customized external tissue expansion device was developed to apply negative pressure to the dorsum of nude mice. The mice were subjected to several treatment courses consisting of 15 and 30 min of continuous negative pressure at 10 mmHg, which were repeated 5 and 10 times every other day until sacrifice. Dorsal skin samples were subsequently extracted from the suction and nonsuction areas. The sections were stained with various antibodies to assess the expression of SOX-9, LHX-2, Keratin-15, β-catenin, CD31, and vascular endothelial growth factor-A, and a TUNEL assay was used to analyze cell apoptosis. The results showed that the number of hair follicles and angiogenesis were significantly higher in the suction area than in the nonsuction area in all groups. Moreover, mice that received NPT for 15 min for 10 times had a higher hair follicle density than the other three groups. Immunofluorescence staining for LHX-2 and Keratin 15 further validated the results of these findings. In conclusion, this study demonstrated that negative pressure effectively promotes hair follicle growth and angiogenesis in nude mice through SOX-9- and LHX-2-mediated follicular regeneration and β-catenin-mediated hair follicle morphogenesis. Impact Statement The results of this study indicate that negative pressure therapy (NPT) is effective in promoting hair growth in nude mice, as evidenced by increased hair follicle density and angiogenesis in the treated areas. Using a custom external tissue expansion device (ETED) device, 15-min NPT treatment conducted over 10 sessions demonstrated the highest follicle density. This suggest that developing a regimen for NPT may offer to create innovative treatment approaches for hair loss, ultimately benefiting individuals suffering from hair loss disorders.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"712-719"},"PeriodicalIF":3.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295408","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":"Reendothelialization of Acellular Adipose Flaps under Mimetic Physiological Dynamic Conditions.","authors":"Yaling Yu, Hui Liu, Ling Xu, Ping Hu, Ning Cui, Jinyi Long, Xue Wu, Da Long, Zhengbing Zhou","doi":"10.1089/ten.TEA.2023.0340","DOIUrl":"10.1089/ten.TEA.2023.0340","url":null,"abstract":"<p><p>The extensive soft-tissue defects resulting from trauma and tumors pose a prevalent challenge in clinical practice, characterized by a high incidence rate. Autologous tissue flap transplantation, considered the gold standard for treatment, is associated with various drawbacks, including the sacrifice of donor sources, postoperative complications, and limitations in surgical techniques, thereby impeding its widespread applicability. The emergence of tissue-engineered skin flaps, notably the acellular adipose flap (AAF), offers potential alternative solutions. However, a critical concern confronting large-scale tissue-engineered skin flaps currently revolves around the reendothelialization of internal vascular networks. In our study, we have developed an AAF utilizing perfusion decellularization, demonstrating excellent physical properties. Cytocompatibility experiments have confirmed its cellular safety, and cell adhesion experiments have revealed spatial specificity in facilitating endothelial cells adhesion within the adipose flap scaffold. Using a novel mimetic physiological fluid shear stress setting, endothelial cells were dynamically inoculated and cultured within the acellular vascular network of the pedicled AAF in our research. Histological and gene expression analyses have shown that the mimetic physiological fluid dynamic model significantly enhanced the reendothelialization of the AAF. This innovative platform of acellular adipose biomaterials combined with hydrodynamics may offer valuable insights for the design and manufacturing of 3D vascularized tissue constructs, which can be applied to the repair of extensive soft-tissue defects. Impact Statement This study investigated reendothelialization of the acellular adipose flap (AAF) using 2D and 3D culture models <i>in vitro</i>. Under 2D conditions, AAF regulated endothelial cells morphology with spatial differences. A 3D mimetic physiological hydrodynamics culture model was constructed to investigate the AAF reendothelialization. Exposure of endothelial cells to physiologically fluid shear stress improved the AAF reendothelialization and increased the expression of the extracellular matrix-integrins-cytoskeleton pathway. Conversely, exposure to nonphysiological hydrodynamics and static environments decreased the reendothelialization. These findings suggest that the platform of AAF combined with physiological hydrodynamics can be applied to construct vascularized tissues to repair large-scale soft-tissue defects.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"693-703"},"PeriodicalIF":3.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140337850","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":"Biogelx-IKVAV Is An Innovative Human Platelet Lysate-Adipose-Derived Stem Cells Delivery Strategy to Improve Peripheral Nerve Repair.","authors":"Martino Guiotto, Alison Clayton, Ryan Morgan, Wassim Raffoul, Andrew Hart, Mathis Riehle, Pietro di Summa","doi":"10.1089/ten.TEA.2023.0307","DOIUrl":"10.1089/ten.TEA.2023.0307","url":null,"abstract":"<p><p>Adipose-derived stem cells (ADSC) are nowadays one of the most exploited cells in regenerative medicine. They are fast growing, capable of enhancing axonal elongation, support and locally stimulate Schwann cells (SCs), and protect de-innervated muscles from atrophy after a peripheral nerve injury. With the aim of developing a bio-safe, clinically translatable cell-therapy, we assessed the effect of ADSC pre-expanded with human platelet lysate in an <i>in vivo</i> rat model, delivering the cells into a 15 mm critical-size sciatic nerve defect embedded within a laminin-peptide-functionalized hydrogel (Biogelx-IKVAV) wrapped by a poly-ɛ-caprolactone (PCL) nerve conduit. ADSC retained their stemness, their immunophenotype and proliferative activity when tested <i>in vitro</i>. At 6 weeks post-implantation, robust regeneration was observed across the critical-size gap as evaluated by both the axonal elongation (anti-NF 200) and SC proliferation (anti-S100) within the human ADSC-IKVAV filled PCL conduit. All the other experimental groups manifested significantly lower levels of growth cone elongation. The histological gastrocnemius muscle analysis was comparable with no quantitative significant differences among the experimental groups. Taken together, these results suggest that ADSC encapsulated in Biogelx-IKVAV are a potential path to improve the efficacy of nerve regeneration. New perspectives can be pursued for the development of a fully synthetic bioengineered nerve graft for the treatment of peripheral nerve injury. Impact statement Human adipose-derived stem cells pre-expanded <i>in vitro</i> with human platelet lysate culture medium additive and encapsulated into BiogelX-IKVAV are a promising strategy to improve nerve regeneration through a critical nerve gap in rat model.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"681-692"},"PeriodicalIF":3.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140121495","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":"Acrylated Hyaluronic-Acid Based Hydrogel for the Treatment of Craniofacial Volumetric Muscle Loss.","authors":"Lucas Rohrer, Shinji Kato, Shane A Browne, Katharine Striedinger-Melo, Kevin Healy, Jason H Pomerantz","doi":"10.1089/ten.TEA.2023.0241","DOIUrl":"10.1089/ten.TEA.2023.0241","url":null,"abstract":"<p><p>Current treatment options for craniofacial volumetric muscle loss (VML) have disadvantages and cannot fully restore normal function. Bio-inspired semisynthetic acrylated hyaluronic acid (AcHyA) hydrogel, which fills irregularly shaped defects, resembles an extracellular matrix, and induces a minimal inflammatory response, has shown promise in experimental studies of extremity VML. We therefore sought to study AcHyA hydrogel in the treatment of craniofacial VML. For this, we used a novel model of masseter VML in the rat. Following the creation of a 5 mm × 5 mm injury to the superficial masseter and administration of AcHyA to the wound, masseters were explanted between 2 and 16 weeks postoperatively and were analyzed for evidence of muscle regeneration including fibrosis, defect size, and fiber cross-sectional area (FCSA). At 8 and 16 weeks, masseters treated with AcHyA showed significantly less fibrosis than nonrepaired controls and a smaller decrease in defect size. The mean FCSA among fibers near the defect was significantly greater among hydrogel-repaired than control masseters at 8 weeks, 12 weeks, and 16 weeks. These results show that the hydrogel mitigates the fibrotic healing response and wound contracture. Our findings also suggest that hydrogel-based treatments have potential use as a treatment for the regeneration of craniofacial VML and demonstrate a system for evaluating subsequent iterations of materials in VML injuries. Impact Statement Craniofacial volumetric muscle loss (VML) is a debilitating condition for which current treatment options are unable to restore normal appearance, or function. Tissue engineering approaches, such as hydrogel implants, may be an effective strategy to fill the volumetric defects and promote <i>de novo</i> muscle regeneration. In this study, we describe a novel rodent model for the study of craniofacial VML and a hyaluronic acid-based hydrogel that can be used as a treatment for the regeneration of craniofacial VML.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"704-711"},"PeriodicalIF":3.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295406","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":"Incorporating Microbial Stimuli for Osteogenesis in a Rabbit Posterolateral Spinal Fusion Model.","authors":"Nada Ristya Rahmani, Anneli Duits, Michiel Croes, Olivia Lock, Debby Gawlitta, Harrie Weinans, Moyo C Kruyt","doi":"10.1089/ten.TEA.2024.0064","DOIUrl":"10.1089/ten.TEA.2024.0064","url":null,"abstract":"<p><p>Autologous bone grafts are commonly used to repair defects in skeletal tissue, however, due to their limited supply there is a clinical need for alternatives. Synthetic ceramics present a promising option but currently lack biological activity to stimulate bone regeneration. One potential approach to address this limitation is the incorporation of immunomodulatory agents. In this study, we investigate the application of microbial stimuli to stimulate bone formation. Three different microbial stimuli were incorporated in a biphasic calcium phosphate (BCP) ceramic: Bacille Calmette-Guérin (BCG), gamma-irradiated <i>Staphylococcus aureus (</i>γi-<i>S. aureus)</i>, or γi<i>-Candida albicans</i> (γi<i>-C. Albicans</i>). The constructs were then implanted in both a rabbit posterolateral spinal fusion (PLF) and an intramuscular implant model for 10 weeks and compared to a nonstimulated control construct. For the PLF model, the formation of a bony bridge was evaluated by manual palpation, micro computed tomography, and histology. While complete fusion was not observed, the BCG condition was most promising with higher manual stiffness and almost twice as much bone volume in the central fusion mass compared to the control (9 ± 4.4% bone area vs. 4.6 ± 2.3%, respectively). Conversely, the γi-<i>S. aureus</i> or <i>γi-C. albicans</i> appeared to inhibit bone formation (1.4 ± 1.4% and 1.2 ± 0.6% bone area). Bone induction was not observed in any of the intramuscular implants. This study indicates that incorporating immunomodulatory agents in ceramic bone substitutes can affect bone formation, which can be positive when selected carefully. The readily available and clinically approved BCG showed promising results, which warrants further research for clinical translation.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333476","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}