Yanli Liu, Qiang Wu, Wanlu Zhao, Xu Song, Fengxing Ding, Wanxian Du, Muting Niu, Yue Zhao, Bo Yuan, Hai Lin, Kai Zhang, Bin Ma
{"title":"Applications of Tissue-Inducing Biomaterials in Nonosseous Tissues: Evidence Map of Animal Studies.","authors":"Yanli Liu, Qiang Wu, Wanlu Zhao, Xu Song, Fengxing Ding, Wanxian Du, Muting Niu, Yue Zhao, Bo Yuan, Hai Lin, Kai Zhang, Bin Ma","doi":"10.1177/19373341251374154","DOIUrl":"10.1177/19373341251374154","url":null,"abstract":"<p><p>Tissue-inducing biomaterials, which promote tissue regeneration without the addition of exogenous cells and/or bioactive factors, have recently attracted increasing interest in the repair of nonosseous tissues. As a key strategy for transforming data into actionable evidence, evidence-based biomaterials research plays a critical role in guiding material development. In this study, evidence mapping method was employed to systematically analyze and visualize animal study designs, material characteristics, outcome indicators, and evaluation methods, aiming to identify current research trends and emerging focal areas. The results revealed a wide diversity of experimental animal species, with a predominance of small animal models. Among the 19 types of nonosseous tissues investigated, skin, abdominal wall, cartilage, and blood vessels were the most frequently studied. Materials were mainly classified into bio-derived materials, polymers, and composites. Outcome indicators span from macroscopic to molecular levels, with tissue-level indicators being the most commonly applied. Histological analysis served as the primary method for validating inductive effects, supported by gross observation, imaging analysis, molecular biology assays, and biomechanical testing. Overall, tissue-inducing biomaterials show promising potential for nonosseous tissue regeneration. However, challenges remain, including limitations of animal models, short follow-up periods, and insufficient evaluation systems. Future studies should strengthen the alignment between functional validation and clinical needs to promote the translation of these materials from experimental research to clinical application.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"225-236"},"PeriodicalIF":2.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980497","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":"VEGF-A-Mediated Differentiation of Gingival Stem Cells to Endothelial Progenitor-Like Cells.","authors":"Garima Gupta, Sandos Alghamdi, Alaa Redwan, Subodh Kumar, Bhupender Sharma, Charles Spencer, Geeta Ravindran, Toshi Kawai, Rajkumar Lakshmanaswamy, Umadevi Kandalam","doi":"10.1177/19373341261429116","DOIUrl":"https://doi.org/10.1177/19373341261429116","url":null,"abstract":"<p><p>The clinical success of bone regeneration relies on developing a functional, vascularized bone. Insufficient vascularization of tissue constructs remains a challenge in stem cell-based approaches, leading to poor graft integration and necrosis of newly formed bone. To overcome current challenges, using pre-committed stem cells for endothelial lineages is a novel approach to developing a vascularized tissue construct. Human gingiva-derived mesenchymal stem cells (GMSCs) are a unique cell population that is readily accessible, has a high proliferation rate, and exhibits multipotent differentiation. This study aimed to investigate the <i>in vitro</i> differentiation potential of GMSCs into the endothelial lineage. GMSCs were induced with 0, 10, 50, or 100 ng/mL recombinant vascular endothelial growth factor (VEGF) for 1 week. The relative mRNA expressions of vascular cell adhesion molecule 1, protocadherin 12, VEGF receptor 1 (fms-like tyrosine kinase 1), VEGF receptor 2 (kinase insert domain receptor), and platelet endothelial cell adhesion molecule-1 were measured by quantitative reverse transcriptase polymerase chain reaction. The expression of all endothelial marker mRNAs was significantly upregulated in a dose-dependent manner in GMSCs induced by VEGF, and maximum expression was observed at 50 ng/mL VEGF induction. A Matrigel assay demonstrated the tube-forming ability of pre-differentiated GMSCs. Our findings demonstrated that GMSCs have the potential to differentiate into endothelial progenitor-like cells. Thus, our study identifies potential options for using GMSCs as an autologous or allogeneic stem cell source for craniofacial bone regeneration.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261429116"},"PeriodicalIF":2.9,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147500646","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}
Jin-Oh Jeong, Young-Wook Moon, Dong-Ryul Song, Chanwoo Hong, Young Min Ju, Hyung Seong Ryu, James J Yoo, Anthony Atala, Sang Jin Lee
{"title":"3D Printing of Bioactive Glass-Poly(ε-Caprolactone) Scaffolds for Patient-Specific Bone Implants.","authors":"Jin-Oh Jeong, Young-Wook Moon, Dong-Ryul Song, Chanwoo Hong, Young Min Ju, Hyung Seong Ryu, James J Yoo, Anthony Atala, Sang Jin Lee","doi":"10.1177/19373341261426393","DOIUrl":"https://doi.org/10.1177/19373341261426393","url":null,"abstract":"<p><p>Craniofacial bone reconstruction presents significant clinical challenges due to the region's complex anatomy and the need to restore both structural integrity and aesthetic function. This study aimed to enhance bone regeneration at graft sites through the development of an osteoconductive bioactive glass-polymer composite for patient-specific implant (PSI) applications. Composite constructs were fabricated via extrusion-based 3D printing using varying weight ratios of bioactive glass ceramic (BGS-7) and poly(ε-caprolactone) (PCL): 2:8, 4:6, 4.5:5.5, and 5:5. Printing parameters were optimized for each formulation to ensure consistent material flow and structural fidelity. Comprehensive characterization included morphological and elemental analysis via scanning electron microscopy/energy-dispersive X-ray spectroscopy, mechanical testing (compressive, flexural, and tensile), and biological evaluation and osteogenic differentiation of human placental stem cells. Higher BGS-7 content correlated with increased incorporation of phosphate, silicon, and calcium, contributing to enhanced mechanical properties and osteogenic potential. The constructs supported high cell viability, promoted cell adhesion and spreading, and induced osteogenic differentiation, as evidenced by calcium deposition and upregulation of key markers. The high-content BGS-7/PCL (5:5) formulation demonstrated optimal printability and bioactivity and was successfully used to fabricate anatomically accurate, human-scale structure. These findings highlight the potential of BGS-7/PCL composites as scalable, biocompatible, and osteoconductive platforms for craniofacial PSI applications.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341261426393"},"PeriodicalIF":2.9,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147492318","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}
Mengyuan Zhang, Ben Wan, Mouyuan Sun, Jiafei Sun, Yi Zhu, Gang Wu, Ping Sun
{"title":"Harnessing Immunomodulation: How Calcium Phosphate Biomaterials Orchestrate Bone Regeneration.","authors":"Mengyuan Zhang, Ben Wan, Mouyuan Sun, Jiafei Sun, Yi Zhu, Gang Wu, Ping Sun","doi":"10.1089/ten.tea.2025.0091","DOIUrl":"10.1089/ten.tea.2025.0091","url":null,"abstract":"<p><p>The immune system and biomaterials exhibit a well-documented synergistic interplay, essential for bone defect healing. Calcium phosphate (CaP) biomaterials, notably hydroxyapatite, β-tricalcium phosphate, and biphasic calcium phosphate, are widely employed as bone substitutes due to their inherent osteoconductivity. A key challenge for synthetic CaPs is augmenting their osteoinductive potential. Indeed, the limited translation of biomaterials into clinical practice may largely stem from insufficient immunomodulatory understanding. Current evidence reveals the complex host immune response to CaPs, which is mediated by physical and biochemical properties. Harnessing immunomodulatory strategies could bridge inflammatory modulation and osteogenesis, thereby enhancing bone regeneration. This review systematically analyzes recent advances in the molecular mechanisms of immune cell responses to CaPs during bone defect healing, deepening our understanding of immunomodulatory strategies for bone regeneration. Furthermore, key knowledge gaps are highlighted to inspire the development of spatiotemporally responsive CaPs for bone tissue engineering.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"163-184"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478003","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":"Bone Organoids: Bridging Natural Bone with Advanced Organoid Technologies.","authors":"Kaige Mao, Yifan Wang, Sengpav Tong, Bo Li, Zhi He, Cunyang Wang, Chuyue Zhang, Xianzheng Wang, Junyao Cheng, Jianheng Liu, Zheng Wang","doi":"10.1177/19373341251359279","DOIUrl":"10.1177/19373341251359279","url":null,"abstract":"<p><p>Bone tissue engineering has long been a focal point of research, aiming to address critical large segmental bone defects resulting from severe trauma, tumors, and other bone-related diseases. Despite significant advancements in conventional bone tissue engineering, the simulation of the intricate microenvironment characteristic of natural bone tissue remains inadequate. Natural bone is characterized by intricate macroscopic and microscopic architectures, along with a dynamic microenvironment that facilitates processes such as bone formation, remodeling, and repair. Bone organoids-three-dimensional structures that emulate natural bone tissue derived from stem cells-represent a substantial advancement in both bone tissue engineering and precision medicine. These organoids present a promising pathway for enhancing our understanding of bone biology and disease mechanisms. Their unique potential within precision medicine is underscored by their applications in personalized drug testing, disease modeling, and as platforms for regenerative therapies. As this field continues to progress, bone organoids are poised to play an essential role in developing tailored treatment strategies for disorders related to bones. In this review, we summarize the roles of cell types, biomaterials and culture techniques in the construction of bone organoids, and emphasize the key significance of microenvironment in guiding the maturation of bone organoids. In addition, we will discuss the standardization, current limitations, and future directions of bone organoids to provide insights for research and clinical applications.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"185-199"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627871","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":"Tissue-Engineered Nerve Grafts: Material Innovations and Clinical Translation Challenges.","authors":"Huan Lian, Yalu Wang, Qianqian Han, Junzhi Wang","doi":"10.1177/19373341251359656","DOIUrl":"10.1177/19373341251359656","url":null,"abstract":"<p><p>Peripheral nerve injury (PNI) is a common disabling condition primarily caused by trauma, such as traffic accidents and occupational injuries. Traditional treatments for PNI have significant limitations. Tissue-engineered nerve grafts (TENGs), which integrate biomaterials, neurotrophic factors, and seed cells, offer a novel solution for nerve regeneration. This review summarizes recent advances in TENGs, focusing on material optimization, preclinical studies, and challenges. Although TENGs show significant potential in repairing long-segment nerve defects, issues such as long-term safety, functional integration, and scalable production require further research. Future multidisciplinary innovations and optimized production processes may enable broader applications of TENGs in nerve regeneration medicine, providing more effective treatment options for patients.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"200-209"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857161","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":"Amino Acids Enhance the Effects of Dexamethasone on Osteogenesis by Rat Stem Cells.","authors":"Hitomi Nakama, Nozomi Matsuo, Ayano Miyamoto, Hiroshi Maeda, Masataka Yoshikawa","doi":"10.1177/19373341251364546","DOIUrl":"10.1177/19373341251364546","url":null,"abstract":"<p><p>Dental pulp tissue is a desirable cell source for tooth regeneration. However, the extirpation of dental pulp tissue from the tooth root canal causes a partial defect in a sound tooth, which is unacceptable, even for the purpose of tooth regeneration. Moreover, bone or dentine formation by mesenchymal stem cells (MSCs) from dental pulp tissue is slow because of the small number and low proliferative capacity of dental pulp cells containing MSCs. To promote the proliferation and differentiation of MSCs <i>in vitro</i>, a novel accelerator needs to be identified in addition to dexamethasone (Dex), β-glycerophosphate (β-GP), and ascorbic acid (Vc). Therefore, the present <i>in vitro</i> study investigated the effects of L(+)-arginine (Arg) and L(+)-lysine (Lys) as bioactive factors that promote mineralized nodule aggregate formation in MSC subcultures. Bone marrow cells obtained from the femur shafts of rats (rBMCs) were used. Mineralized nodule aggregates were formed by rBMCs in culture medium (MEM: Dulbecco's modified Eagle's medium) for subcultures containing Dex and additional Lys or Arg. Aggregates were decalcified in 10% formic acid to measure the level of Ca<sup>2+</sup> as an indicator of osteo- or odontogenesis. The results obtained suggest that the addition of Arg to the medium for the rBMC subculture enhanced Dex-induced osteogenesis by rMSCs. The level of Ca<sup>2+</sup> in calcified nodule aggregates obtained from the rBMC subculture was significantly smaller in MEM containing Dex (MEM-Dex (+)) than in that with 1.150 mmol of Arg (<i>p</i> < 0.001). No significant differences were observed in the level of Ca<sup>2+</sup> in aggregates formed by rBMCs between MEM-Dex (+) containing 68.4 or 136.8 mmol of Lys or 0.575 mmol of Arg and that without these amino acids (<i>p</i> > 0.05). The level of Ca<sup>2+</sup> measured following the addition of Arg at 1.150 mmol to 2 mL of MEM-Dex (+) was high. These results indicated that Dex in the medium supplemented with Arg as a cofactor actively promoted the osteogenic activity of MSCs.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"210-218"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786025","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}
Beini Mao, Ming Tian, Yuling Yin, Lang Li, Jian Li, Daixu Wei, Weili Fu
{"title":"A Novel Injectable Cell-Loaded Hydrogel System for Cartilage Repair: <i>In Vivo</i> and <i>In Vitro</i> Study.","authors":"Beini Mao, Ming Tian, Yuling Yin, Lang Li, Jian Li, Daixu Wei, Weili Fu","doi":"10.1089/ten.tea.2025.0024","DOIUrl":"10.1089/ten.tea.2025.0024","url":null,"abstract":"<p><p>Polyhydroxyalkanoates are promising biomaterials, but their application in cartilage repair is still limited. In this study, an injectable thermosensitive hydrogel poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate)-Polyethylene Glycol (PEG)/hyaluronic acid/kartogenin was prepared from 3-hydroxybutyrate, 3-hydroxyvalerate, 3-hydroxyhexanoate, hyaluronic acid, and kartogenin. The hydrogels are porous, temperature-sensitive, and hydrophilic and have good compressive modulus. Mesenchymal stem cells derived from peripheral blood can proliferate on the hydrogels under two- and three-dimensional cultures. In addition, the hydrogel has the ability to induce chondrogenic differentiation of stem cells and induce M2 differentiation of macrophages. The hydrogel loaded with peripheral blood mesenchymal stem cells can repair cartilage defects in the knee joints of New Zealand rabbits and the newly formed cartilage was identified as type II collagen. Overall, this newly developed system could provide a new treatment option for repairing cartilage defects.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"149-162"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027722","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}
Autumn C Campbell, Divya Sridharan, Britani N Blackstone, Syed A Ashraf, Dorothy M Supp, Mahmood Khan, Heather M Powell
{"title":"Dermal Templates Support Epidermal Regeneration and Maturation Regardless of Cell Donor Age.","authors":"Autumn C Campbell, Divya Sridharan, Britani N Blackstone, Syed A Ashraf, Dorothy M Supp, Mahmood Khan, Heather M Powell","doi":"10.1177/19373341251409800","DOIUrl":"10.1177/19373341251409800","url":null,"abstract":"<p><p>To provide an optimal wound bed for epidermal regeneration, a viable dermis is needed. As the dermis is destroyed in full-thickness burns, dermal templates (DTs) are used to create a healthy dermis for grafting and other procedures. Neonatal foreskin has exclusively been used as the source of dermal fibroblasts in commercial DTs, as the tissue is readily available and because these cells are assumed to be more proliferative and capable of superior wound healing compared with adult fibroblasts. The goal of this study was to assess the function of adult fibroblasts compared with neonatal fibroblasts for DT construction and epidermal regeneration. Primary fibroblasts were isolated from neonatal or adult surgical discard tissue (n = 4 each). Expression of collagen type 1 A1 (<i>COL1A1)</i> and matrix metalloprotease 1 <i>(MMP1)</i>, <i>MMP3</i>, and <i>MMP9</i> was assessed for each cell strain, and proliferation was quantified in two-dimensional (2D) cultures and 3D DTs. Subsequently, DTs were constructed from each cell strain by inoculating fibroblasts onto electrospun collagen scaffolds. DT contraction, extracellular matrix remodeling, and cell viability were assessed over 7 days in culture, and the ability of the DTs to promote epidermal regeneration was assessed using primary adult keratinocytes. No differences in gene expression were observed in neonatal versus adult fibroblasts in 2D culture. Neonatal fibroblasts were significantly more proliferative at day 7 when cultured in 2D; however, fibroblast proliferation was independent of donor age in 3D culture. Neonatal DTs contracted significantly more than adult DTs (68.8% ± 6.2% vs. 91.7% ± 4.2% original wound area, respectively). Upon seeding with keratinocytes, a robust, stratified epidermis formed in all DT groups, with no statistically significant differences in dermal or epidermal thickness, basal keratinocyte proliferation, epidermal barrier function, or basement membrane deposition. Analysis of gene expression revealed modest differences in the expression of <i>MMP1</i>, <i>COL1A1</i>, and <i>ACTA2</i> in neonatal versus adult engineered skin <i>in vitro</i>, which were not associated with any discernable histological differences. These results indicate that the fabrication of DTs with adult fibroblasts can promote epidermal regeneration equivalent to that of neonatal fibroblasts but with less <i>in vitro</i> contraction, which may enable the treatment of larger wound areas.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341251409800"},"PeriodicalIF":2.8,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13255093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145866422","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}