Tissue engineering and regenerative medicine最新文献

{"title":"Mesenchymal Stem Cell-Derived Exosomes in Skin Wound Healing and Scar Prevention: Mechanisms, Comparison, and Clinical Prospects.","authors":"Yaoyao Song, Fei Xie, Xiangdang Liang","doi":"10.1007/s13770-026-00821-5","DOIUrl":"10.1007/s13770-026-00821-5","url":null,"abstract":"<p><strong>Background: </strong>Exosomes derived from mesenchymal stem cells (MSCs) have garnered significant research interest for their roles in promoting wound healing and preventing scar formation. Studies have shown that MSC-derived exosomes (MSC-Exos) accelerate the repair of cutaneous and corneal wounds through multiple mechanisms, including modulation of cell migration, anti-inflammatory responses, inhibition of apoptosis, collagen remodeling, and promotion of angiogenesis. Notably, exosomal miRNAs play a pivotal role in inhibiting fibroblast-to-myofibroblast transformation and modulating the TGF-β signaling pathway, thereby effectively reducing scar formation. Promising outcomes of exosomes derived from adipose tissue- and umbilical cord blood-derived MSCs in various wound models underscore their clinical potential.</p><p><strong>Methods: </strong>This review systematically elaborates on the specific mechanisms by which MSC-Exos promote wound healing and inhibit scar formation, and summarizes their application outcomes in different wound models. Additionally, it explores current advanced biomaterial delivery systems designed to optimize exosome delivery, aiming to provide insights and future directions for the clinical translation of MSC-Exos.</p><p><strong>Results and conclusion: </strong>MSC-Exos effectively promote tissue repair and reduce scarring through multi-target and multi-pathway mechanisms, demonstrating significant clinical application prospects. Delivery systems incorporating biomaterials hold promise for further enhancing their therapeutic efficacy and stability. Future research should focus on elucidating the molecular mechanisms of exosome action, developing scalable preparation protocols, and conducting preclinical and clinical evaluations to advance their translation into clinical therapeutic applications.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"975-987"},"PeriodicalIF":5.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Bone Healing Using Autogenous Tooth Bone Graft Combined with rhBMP-2 after Enucleation of a Large Odontogenic Keratocyst: A Case Report.","authors":"Seungtae Kim, Jeong-Kui Ku, Yongjun Cho, Jae-Young Kim, Jong-Ki Huh","doi":"10.1007/s13770-026-00827-z","DOIUrl":"10.1007/s13770-026-00827-z","url":null,"abstract":"<p><strong>Background: </strong>Autogenous tooth bone graft (AutoBT), derived from extracted teeth, has emerged as a promising alternative for bone regeneration due to its osteoinductive and osteoconductive properties. Its structural and compositional similarity to bone supports physiologic bone regeneration, and it has been successfully applied in various clinical procedures. However, despite its increasing clinical application, evidence regarding the long-term outcomes of AutoBT in large cystic defects remains limited.</p><p><strong>Case presentation: </strong>A 22-year-old woman presented with a 4-cm multilobular radiolucent lesion in the left mandible that was diagnosed as an odontogenic keratocyst (OKC). Following a period of decompression, cyst enucleation and bone grafting were performed using AutoBT combined with recombinant human bone morphogenetic protein-2 (rhBMP-2). Radiographic follow-up at 1.5 months, 1 year, and 3 years postoperatively demonstrated stable bone remodeling, reestablishment of the cortico-cancellous architecture, and no evidence of recurrence. The postoperative clinical course was uneventful.</p><p><strong>Conclusion: </strong>This case demonstrates successful long-term bone regeneration using AutoBT combined with rhBMP-2 in a large mandibular OKC defect. Although limited to a single case, these findings support the potential of AutoBT combined with rhBMP-2 as a reliable graft material for extensive jawbone lesions. Further studies are needed to validate its long-term efficacy and safety.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"1115-1121"},"PeriodicalIF":5.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148498088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory T Cells in Peri-implant Diseases: Current Osteoimmunologic Perspectives and Translational Challenges.","authors":"Jong Il Yun, Su In Yun, Jae Hong Kim, Duk Gyu Kim, Hyoung-Jun Kim, Jeong-Kui Ku","doi":"10.1007/s13770-026-00840-2","DOIUrl":"10.1007/s13770-026-00840-2","url":null,"abstract":"<p><strong>Background: </strong>Peri-implantitis has become an increasingly important clinical challenge with the growing number of patients receiving dental implants worldwide. Previous peri-implant research has predominantly focused on surgical factors, including implant position, angulation, and design, as well as biofilm-associated infection. In contrast, relatively less attention has been given to host immune regulation. Recent advances in osteoimmunology have highlighted thepotential role of regulatory T cells (Tregs) in infl ammatory control and tissue homeostasis.</p><p><strong>Methods: </strong>This review examines current evidence regarding immune-cell regulation in peri-implant diseases from an osteoimmune perspective. Particular attention is given to the interactions between primary immune cells, especially macrophages, and secondary immune cells, particularly Tregs, as well as their potential roles in peri-implant inflammation and bone responses.</p><p><strong>Results: </strong>Accumulating evidence suggests that bone responses around dental implants are infl uenced by osteoimmune mechanisms. Tregs have emerged as important regulators of infl ammatory processes and may contribute to themaintenance of peri-implant tissue homeostasis. Furthermore, complex interactions between macrophages and Tregs appear to influence local immune conditions surrounding implants. Current studies indicate that osteoimmune regulation may provide additional insights into the pathophysiology of peri-implant diseases and reveal potential targets for immunomodulatory intervention. However, biological limitations and signifi cant knowledge gaps remain regarding the precise role of Tregs in peri-implantitis.</p><p><strong>Conclusion: </strong>An osteoimmune perspective may broaden the current understanding of peri-implant diseases beyond traditional surgical and microbiological paradigms. Treg-mediated immune regulation represents a promising area for future investigation, with potential translational implications for the prevention and management of peri-implantitis.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cord Blood Platelet-Poor Plasma Functionalizes Polycaprolactone Scaffolds for Coupled Vascularization and Osteogenesis in Bone Tissue Engineering.","authors":"Hoang Nhat Tran, Ngoc Minh Vu, Xuan-Hai Do, Trung-Chuc Nguyen, Lan Xuan Phung, Duy Duc Le, Hieu Dung Dinh, Uyen Thi Trang Than, Lung Tien Nguyen, Xuan-Kien Dang, Bich Thi Pham, Nhung Thi My Hoang","doi":"10.1007/s13770-026-00841-1","DOIUrl":"https://doi.org/10.1007/s13770-026-00841-1","url":null,"abstract":"<p><strong>Background: </strong>Angiogenesis is critical for the success of 3D scaffolds in bone tissue engineering. This study investigated the use of platelet-poor plasma (PPP) derived from umbilical cord blood (UCB) as a bioactive coating agent to impart osteo-inductive, angiogenic, and immunomodulatory properties to 3D-printed polycaprolactone (PCL) scaffolds.</p><p><strong>Methods: </strong>PCL scaffolds were coated with UCB-PPP and evaluated in vitro for cell adhesion, proliferation, extracellular matrix (ECM) expression, and osteogenic differentiation of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and fibroblasts (hFBs). In vitro angiogenesis was evaluated via the tube formation of human umbilical vein-derived endothelial cells. In vivo neovascularization and tissue integration were assessed using a subcutaneous mouse implantation model, alongside immunogenicity testing using rat and human allogeneic mononuclear cells.</p><p><strong>Results: </strong>The PPP coating proved highly effective, enhancing adhesion and proliferation of hUC-MSCs and hFBs by upregulating ECM components and pro-regenerative cytokines. In vitro, PPP coating promoted osteoblast differentiation of hUC-MSCs, as evidenced by increased calcium deposition and expression of osteoprogenitor markers. Crucially, the PPP coating stimulated robust in vitro tube formation and in vivo subcutaneous neovascularization, evidenced by functional, erythrocyte-perfused endothelial lumens, elevated VEGF-A expression, and M2 macrophage polarization. Moreover, PPP-coated scaffolds demonstrated low immunogenicity in both rat and human allogeneic mononuclear cells, thereby supporting preclinical safety and immunomodulation.</p><p><strong>Conclusions: </strong>UCB-PPP serves as an immune-tolerant, highly bioactive coating that functionalizes inert PCL scaffolds by promoting in vitro osteogenesis and in vivo functional vascular integration. This dual-action strategy provides a promising proof-of-concept for addressing vascularization bottlenecks in bone tissue engineering applications.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Geometry-Dependent Osteogenic Performance of Demineralized Dentin Matrix as a Carrier for rhBMP-2.","authors":"Jin-Won Choi, In-Woong Um, Yeong Kon Jeong, Pil-Young Yun, Jeong-Kui Ku","doi":"10.1007/s13770-026-00836-y","DOIUrl":"https://doi.org/10.1007/s13770-026-00836-y","url":null,"abstract":"<p><strong>Background: </strong>Demineralized dentin matrix (DDM) is a bioactive collagen-based scaffold with intrinsic osteoinductive properties and potential as a carrier for recombinant human bone morphogenetic protein-2 (rhBMP-2). However, the influence of DDM geometry on its osteogenic performance and carrier efficiency remains unclear. This study aimed to evaluate the geometry-dependent osteogenic efficacy of DDM and its role as an rhBMP-2 delivery system.</p><p><strong>Methods: </strong>DDM was prepared in particulate (300-800 µm) and block forms (root segments with drilled pores) and compared with an absorbable collagen sponge in a subcutaneous implantation model using nude mice. Each carrier was evaluated with no rhBMP-2 or with low-dose (1 µg) or high-dose (2 µg) rhBMP-2 at 2 and 4 weeks. New bone formation was assessed using micro-computed tomography and histological/histomorphometric analyses.</p><p><strong>Results: </strong>Both forms of DDM demonstrated intrinsic osteoinductive capacity, inducing ectopic bone formation without exogenous rhBMP-2, whereas collagen alone showed negligible bone formation. Particulate DDM exhibited greater bone formation than block DDM, with the difference reaching statistical significance by 4 weeks. The addition of rhBMP-2 enhanced early bone formation, particularly at 2 weeks; however, by 4 weeks, DDM alone achieved comparable outcomes. Notably, particulate DDM with low-dose rhBMP-2 produced bone formation comparable to or greater than that achieved with high-dose rhBMP-2 in collagen carriers. Histological findings confirmed that DDM provided sustained osteogenesis with direct bone formation on the scaffold surface, while collagen carriers exhibited peripheral bone formation due to rapid rhBMP-2 release.</p><p><strong>Conclusion: </strong>DDM is an effective osteoinductive scaffold and a superior carrier for rhBMP-2 compared to collagen. Its osteogenic performance is geometry-dependent, with particulate DDM demonstrating enhanced bone regeneration. Importantly, DDM enables effective bone formation with reduced rhBMP-2 dosage, suggesting a safer and more efficient strategy for bone regeneration.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Status of Animal Models for Premature Ovarian Insufficiency: Similarities to Clinical Manifestations and Therapeutic Applications.","authors":"Bunnith Theng, Yoon Young Kim, Ji Yeon Han, Seung-Yup Ku","doi":"10.1007/s13770-026-00834-0","DOIUrl":"https://doi.org/10.1007/s13770-026-00834-0","url":null,"abstract":"<p><strong>Background: </strong>Premature ovarian insufficiency (POI) is a reproductive disorder characterized by the early loss of ovarian function before the age of 40, resulting in infertility and increasing the long-term risk of health issues such as osteoporosis, cardiovascular disease, and neuropsychological disorders. Although many studies have been conducted to understand POI pathophysiology and to develop regenerative therapies, the effectiveness of these therapies in restoring ovarian function remains limited. This review provides a comprehensive evaluation of the establishment of animal models of POI and assesses their similarity to clinical manifestations and therapeutic outcomes observed in human patients.</p><p><strong>Methods: </strong>Published preclinical and clinical studies investigating POI animal models and regenerative therapies were comprehensively reviewed. Animal models were compared with human POI in terms of pathological features, endocrine changes, and therapeutic responsiveness. Evidence from studies of mesenchymal stem cell (MSC)-based therapies, stem cell-derived extracellular vehicles (EVs), platelet-rich plasma (PRP), and scaff old-assisted combination therapies was integrated.</p><p><strong>Results: </strong>POI models induced by chemotherapeutic agents, autoimmune mechanisms, or oxidative stress reproduce POI features, including follicular depletion, disrupted estrous cycles, and altered hormone profiles. However, they do not fully capture the systemic progression of the condition that is observed in human patients. We summarize emerging regenerative treatment strategies, including mesenchymal stem cell-based therapies, stem cell-derived exosome-like extracellular vesicles (EVs), platelet-rich plasma, and scaffold-assisted combination therapies, combining findings from both preclinical experiments and clinical studies. Comparing shared outcome markers, such as estradiol levels and follicle counts, while emphasizing age- and duration-of-amenorrhea differences in treatment response, is critical for assessing therapeutic efficacy, with younger patients and those with shorter disease duration showing more favorable responses.</p><p><strong>Conclusions: </strong>Current rodent models provide valuable insights but have limited ability to predict clinical efficacy. Further POI research should prioritize the development of more physiologically relevant models, such as non-human primates, which more closely resemble humans in both reproductive endocrinology and aging, omics approaches, and artificial intelligence (AI), which may significantly enhance the translational accuracy of POI research.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Promoter-Targeted CRISPR Correction of PMP22 Gene Dosage Restores Schwann Cell Homeostasis in Charcot-Marie-Tooth Disease Type 1A.","authors":"Hyun Myung Doo, Soo Hyun Nam, Haeun Kim, Kang In Lee, Jae Young Lee, So Hyang Park, Yang Ji Kim, Byung-Ok Choi, Jong Hyun Kim","doi":"10.1007/s13770-026-00837-x","DOIUrl":"https://doi.org/10.1007/s13770-026-00837-x","url":null,"abstract":"<p><strong>Background: </strong>Charcot-Marie-Tooth disease type 1A (CMT1A), the most common inherited peripheral neuropathy, arises from a 1.4 Mb duplication of the Peripheral Myelin Protein 22 (PMP22) gene, causing gene-dosage-dependent toxic overexpression that drives Schwann cell dysfunction and demyelination. We developed a gene-dosage-targeted therapeutic strategy using an sgRNA-mediated bidirectional promoter microdeletion (sgRNA-BPM) approach to selectively suppress pathogenic PMP22 overexpression while preserving physiological expression levels.</p><p><strong>Methods: </strong>Clinical evaluation of an index patient (pedigree analysis, muscle MRI, electrophysiological assessment) confirmed an inherited demyelinating neuropathy with distal muscle atrophy. Patient-derived pluripotent stem cells (iPSCs) were used to establish a single-cell-derived clone in which all three PMP22 P1 promoter TATA boxes were disrupted (- 2, - 2, and - 17 bp deletions). This promoter-targeted editing attenuated PMP22 expression during directed differentiation into Schwann cell lineage.</p><p><strong>Results: </strong>Edited cells exhibited partial restoration of Schwann cell maturation-associated, promyelinating-like transcriptional features, accompanied by upregulation of SOX9 and AP2α, attenuation of aberrant PMP22 overexpression, and improvement of Schwann cell morphology. Quantitative imaging revealed ~ 50% reduction (p < 0.01) in PMP22/S100β co-expression index, indicating substantial molecular and structural correction. Despite P1 promoter disruption, basal PMP22 expression was preserved, consistent with transcription driven by the downstream TATA-less P2 promoter. This promoter-level repression of PMP22 was reproducible in mature human primary Schwann cells, where quantitative PCR confirmed reduced PMP22 expression (p < 0.05), supporting translational feasibility of this gene-dosage modulation strategy beyond iPSC-derived systems.</p><p><strong>Conclusions: </strong>Collectively, patient-anchored, promoter-targeted genome editing can potentially correct pathogenic PMP22 dosage while preserving basal expression, establishing a translational iPSC-based framework for treating dosage-sensitive demyelinating neuropathies such as CMT1A.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of the Chondrogenic Potential of Synovial Membrane-Derived Mesenchymal Stem Cells Prepared Using Different Culture Methods for Temporomandibular Joint Disc Perforation Repair in Rabbits.","authors":"Wang Lihua, Zhang Zhoujing, Xu Wenyan, Yang Lu, Yang Rui, Zou Duohong, Zhou Yong","doi":"10.1007/s13770-026-00838-w","DOIUrl":"https://doi.org/10.1007/s13770-026-00838-w","url":null,"abstract":"<p><strong>Background: </strong>This study investigated the chondrogenic potential of synovial membrane mesenchymal stem cells (SMSCs) under varying culture conditions and their impact on disc defect regeneration.</p><p><strong>Methods: </strong>SMSCs were isolated from the rabbit synovium by an enzymatic method (E-SMSCs) or explant method (T-SMSCs). Then, SMSCs were cultured with transforming growth factor-β3 (TGFβ3) alone or in combination with bone morphogenic protein-2 (BMP2). The expression of chondrogenesis-related markers and the content of glycosaminoglycans (GAGs) were tested to evaluate chondrogenesis. Thirty temporomandibular joint (TMJ) discs were harvested from 15 rabbits. A 2 mm defect was created on each of the discs and transplanted with SMSC cell pellets into nude mice subcutaneously to investigate ectopic chondrogenic ability in vivo.</p><p><strong>Results: </strong>Both isolation techniques can achieve successful isolation of SMSCs from the synovium. Higher cellular proliferation was achieved by explant culture. When the induction solution contained only TGFβ3, T-SMSCs expressed more genes related to chondrogenesis and produced more GAGs. E-SMSCs demonstrated enhanced chondrogenic potential both in vitro and in vivo when treated with TGFβ3 and BMP2.</p><p><strong>Conclusion: </strong>Both E-SMSCs and T-SMSCs expressed cartilage-specific markers in TGFβ3 medium. E-SMSCs demonstrated enhanced chondrogenic potential after induction with TGF-β3 and BMP2, both in vitro and in vivo.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterogeneous Spheroid Engineering: Spatial Organization, Fabrication, and Tissue-Specific Design.","authors":"Seungji Baek, Yeonwoo Jang, Hansoo Park","doi":"10.1007/s13770-026-00839-9","DOIUrl":"https://doi.org/10.1007/s13770-026-00839-9","url":null,"abstract":"<p><p>Three-dimensional (3D) spheroid models have emerged as advanced in vitro systems that overcome the limitations of conventional two-dimensional (2D) culture by better recapitulating native tissue architecture, cell-cell and cell-extracellular matrix interactions, and physiologically relevant gradients of oxygen, nutrients, and signaling factors, making them valuable platforms for tissue engineering and regenerative medicine. Realizing their full potential, however, requires rational control over cellular composition and spatial organization. In this review, we classify spheroids by cellular composition and spatial organization into single-cell-type and heterogeneous architectures-including mixed, core-shell, assembloid, and embedded co-culture configurations. We then summarize principal fabrication strategies encompassing static methods, dynamic suspension systems, and scaffold-based approaches. Spatially organized heterogeneous spheroids consistently enhance cell survival, paracrine signaling, vascularization, and tissue-specific differentiation relative to single-cell-type counterparts. We discuss applications across musculoskeletal, cardiovascular, nervous, epithelial, hepatic, pancreatic, renal, and urogenital tissues, highlighting how spatial design governs functional outcomes in each context. Spatial organization and fabrication strategy are decisive determinants of spheroid function for regenerative applications. Persistent challenges in vascularization, standardization, and scalable manufacturing must be addressed to enable reliable clinical translation, while emerging engineering approaches offer promising routes toward functional tissue constructs.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peptide Dissolved in Alkaline Buffer with Blocking Significantly Enhances Performance of Synthetic Peptide-Displaying Surfaces in Supporting Human Pluripotent Stem Cell Culture.","authors":"Shengqin Ma, Liying Qin, Shaodong Wang, Ting Meng, Zhengyan Zhao, Maoying Liu, Chuan Zhang, Fang Wu, Ping Zhou","doi":"10.1007/s13770-026-00835-z","DOIUrl":"https://doi.org/10.1007/s13770-026-00835-z","url":null,"abstract":"<p><strong>Background: </strong>Human pluripotent stem cells (hPSCs) offer vast potential for cellular therapies due to their unique abilities in self-renewal and differentiation. However, the reliance on animal-derived Matrigel in conventional cell culture limits clinical translation, and developing chemically defined synthetic surfaces remains a key technical challenge.</p><p><strong>Methods: </strong>Based on our previously established synthetic polydopamine-based peptide-displaying surfaces, this study systematically optimized each fabrication step, including substrate selection, raw material screening (dopamine, carboxymethyl chitosan), reaction conditions, post-conjugation medium blocking, and peptide-dissolving buffer systems. Molecular docking was performed to analyze peptide-integrin αVβ5 interactions, and findings were verified using alginate-gelatin hydrogel and Maleylated-BSA coatings.</p><p><strong>Results: </strong>Compared with commercial plates, pure polystyrene plates showed better abilities in sustaining cell culture, and the optimal raw materials for dopamine and carboxymethyl chitosan as well as their ideal reaction conditions were identified. Interestingly, not only does medium blocking after peptide conjugation play a crucial role, but the use of alkaline peptide-dissolving buffers also provides a significant advantage in supporting hPSCs adhesion and self-renewal. Molecular docking revealed enhanced peptide-integrin αVβ5 binding energetics under alkaline conditions. The optimized peptide-displaying surface demonstrated superior performance in supporting hPSCs culture and differentiation.</p><p><strong>Conclusion: </strong>Our study reveals several previously unknown critical factors in the preparation of synthetic peptide-displaying surfaces. The optimized protocol improves hPSC culture performance and provides a reliable foundation for advancing chemically defined, animal component-free coatings toward commercial and clinical applications.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}