Tissue Engineering Part A最新文献

{"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":"https://doi.org/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":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-24","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":"<i>In Vivo</i> Differentiation of hESC-Derived Neural Crest Cells into Trabecular Meshwork Cells.","authors":"Ying Su, Haoyun Duan, Hai Zhu, Chunxiao Dong, Dulei Zou, Qianwen Bu, Wei Zhu, Qingjun Zhou, Zongyi Li, Xiaojing Pan","doi":"10.1089/ten.tea.2024.0343","DOIUrl":"https://doi.org/10.1089/ten.tea.2024.0343","url":null,"abstract":"<p><p>Primary open-angle glaucoma is a prevalent type of degenerative eye disease that results in lifelong blindness, and its critical pathogenic cause is trabecular meshwork (TM) dysfunction or decreased TM cellularity. Considering that TM develops from neural crest cells (NCCs), we investigate the potential of human embryonic stem cell (hESC)-derived NCCs transplantation for TM regeneration. We used a chemically defined method to induce the differentiation of NCCs and injected 1.0 × 10⁶ hESC-derived NCCs combined with 100 μmol/L Y-27632 into the anterior chamber of rabbit. Intraocular pressure (IOP), TM, and corneal changes of rabbits with cell transplantation were examined with TonoPEN AVIA, slit lamp microscope, dual-immunofluorescence staining, and optical coherence tomography. The hESC-derived NCCs underwent homogenous differentiation over the course of 5 days' induction, which expressed the typical neural crest markers HNK-1, P75, SOX10, and AP-2α. NOD/SCID mice received injections of hESC-derived NCCs in the groin or axilla. There was no teratoma formation. When intracamerally injected, hESC-derived NCCs integrated into the TM tissue and expressed mature TM cell markers <i>Aqp1</i>, <i>Chi3l1</i>, and <i>Timp3</i> after 7 days transplantation in rabbit eyes. The IOP and central corneal thickness basically maintained at normal levels within 2 weeks. No significant adverse effects in rabbits with hESC-derived NCC injection were observed after 5 weeks of cell transplantation. Our findings indicate that hESC-derived NCCs could integrate into the TM tissue and differentiate into mature TM cells after being injected intracamerally, showing a potential therapeutic approach to addressing TM dysfunction in the treatment of glaucoma. Impact Statement Glaucoma is the leading cause of irreversible blindness that poses a substantial burden on public health and the quality of life of affected individuals. We found human embryonic stem cell (hESC)-derived NCCs integrated into the trabecular meshwork (TM) tissue, and expressed mature TM cell markers Aqp1, Chi3l1, and Timp3 after intracameral injection. The results also highlighted hESC-derived NCC treatment's safety, with no treatment-related serious adverse events during the long-term follow-up. These findings suggest that hESC-derived NCCs offer potential for new interventions for the therapy of glaucoma.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303663","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":"Optimizing Bioactive Glass-Nanoparticle-Polymer Blend Scaffolds: A Shift in Bone Regeneration Design.","authors":"Duangruedee Khwannimit, Ayuth Vejpongsa, Thanaphum Wannalobon, Juthatip Manissorn, Patsawee Sriboonaied, Apipon Methachittipan, Aruna Prasopthum, Phakaorn Phuyuttakarin, Khaow Tonsomboon, Peerapat Thongnuek","doi":"10.1089/ten.tea.2024.0347","DOIUrl":"https://doi.org/10.1089/ten.tea.2024.0347","url":null,"abstract":"<p><p>Scaffolds for bone tissue engineering have traditionally been designed to mimic the inorganic-to-organic ratio of mature bone, aiming to recapitulate its mechanical properties. However, early bone repair is not characterized by immediate mechanical strength but rather by materials that highly promote osteogenesis. In this study, we present the fabrication and evaluation of composite scaffolds composed of bioactive glass nanoparticles (BGNPs), silk fibroin, gelatin, and alginate, designed to optimize the ratio of inorganic BGNPs to biological polymers to enhance both biocompatibility and osteogenic potential. Characterization of the scaffolds revealed that the balance between BGNP and polymer content significantly influenced their structural and functional properties. Thermogravimetric analysis (TGA) showed a positive correlation between polymer content and scaffold water retention, while differential TGA(DTG) indicated that BGNPs improved the thermal stability of the polymer matrix. Swelling and biodegradation studies demonstrated that scaffolds with higher polymer content absorbed more water and degraded faster, creating a more dynamic environment conducive to cell activity. Uniaxial compression testing demonstrated that scaffolds with balanced compositions exhibited mechanical properties resembling those of the soft callus. In vitro biocompatibility tests demonstrated that scaffolds with higher polymer content were noncytotoxic, whereas those with excessive BGNPs reduced cell viability. Scaffolds with balanced compositions (Polymer blend: BGNPs = 9:1 and 7:3) showed significantly enhanced cell viability and osteogenicity, as indicated by increased alkaline phosphatase activity. Surprisingly, the optimal ratios resembled those of the soft callus, rather than mature bone. Based on these findings, we propose that scaffold designs should mimic the inorganic-to-organic composition of the soft callus, formed in the early stages of bone repair, as this composition better promotes osteogenesis. Optimizing the BGNP-to-polymer ratio is crucial for creating biomaterials that will achieve long-term clinical success.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259465","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":"Endothelial Cells Increase Mesenchymal Stem Cell Differentiation in Scaffold-Free 3D Vascular Tissue.","authors":"William G DeMaria, Andre E Figueroa-Milla, Abigail Kaija, Anne E Harrington, Benjamin Tero, Larisa Ryzhova, Lucy Liaw, Marsha W Rolle","doi":"10.1089/ten.TEA.2024.0122","DOIUrl":"10.1089/ten.TEA.2024.0122","url":null,"abstract":"<p><p>In this study, we present a versatile, scaffold-free approach to create ring-shaped engineered vascular tissue segments using human mesenchymal stem cell-derived smooth muscle cells (hMSC-SMCs) and endothelial cells (ECs). We hypothesized that incorporation of ECs would increase hMSC-SMC differentiation without compromising tissue ring strength or fusion to form tissue tubes. Undifferentiated hMSCs and ECs were co-seeded into custom ring-shaped agarose wells using four different concentrations of ECs: 0%, 10%, 20%, and 30%. Co-seeded EC and hMSC rings were cultured in SMC differentiation medium for a total of 22 days. Tissue rings were then harvested for histology, Western blotting, wire myography, and uniaxial tensile testing to examine their structural and functional properties. Differentiated hMSC tissue rings comprising 20% and 30% ECs exhibited significantly greater SMC contractile protein expression, endothelin-1 (ET-1)-meditated contraction, and force at failure compared with the 0% EC rings. On average, the 0%, 10%, 20%, and 30% EC rings exhibited a contractile force of 0.745 ± 0.117, 0.830 ± 0.358, 1.31 ± 0.353, and 1.67 ± 0.351 mN (mean ± standard deviation [SD]) in response to ET-1, respectively. Additionally, the mean maximum force at failure for the 0%, 10%, 20%, and 30% EC rings was 88.5 ± 36. , 121 ± 59.1, 147 ± 43.1, and 206 ±  0.8 mN (mean ± SD), respectively. Based on these results, 30% EC rings were fused together to form tissue-engineered blood vessels (TEBVs) and compared with 0% EC TEBV controls. The addition of 30% ECs in TEBVs did not affect ring fusion but did result in significantly greater SMC protein expression (calponin and smoothelin). In summary, co-seeding hMSCs with ECs to form tissue rings resulted in greater contraction, strength, and hMSC-SMC differentiation compared with hMSCs alone and indicates a method to create a functional 3D human vascular cell coculture model. Impact Statement The goal of this work is to create an <i>in vitro</i> vascular model that exhibits structural and functional properties similar to those of native vascular tissue. For the first time, we demonstrated that human mesenchymal stem cells cocultured with endothelial cells as 3D cell aggregates, differentiated into smooth muscle cells, exhibited contractile protein expression, and contracted in response to endothelin-1. These tissue rings could be fused together to form cohesive tubular constructs to mimic the geometry of native vasculature. Overall, this study demonstrated a novel method to create and assess 3D human vascular tissue constructs using quantitative metrics.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"456-470"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12184959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899052","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":"The Impact of Vascular Supply on Endochondral Bone Regeneration in Centimeter-Sized Porous Chambers.","authors":"Leanne S de Silva, Casper J Kuijpers, Ellen M Van Cann, Antoine J W P Rosenberg, Robert J J van Es, Debby Gawlitta","doi":"10.1089/ten.tea.2025.0045","DOIUrl":"https://doi.org/10.1089/ten.tea.2025.0045","url":null,"abstract":"<p><p>The current clinical treatment of large bone defects in humans primarily relies on autologous bone grafts. However, the use of autologous bone grafts can be limited by tissue availability, variable bone quality, and donor site morbidity. In response to these challenges, endochondral bone regeneration has emerged as a promising approach. This method mimics endochondral ossification by chondrogenically differentiating or stimulating cells of various cell sources into 'callus mimics' (CMs). We previously demonstrated the feasibility of endochondral bone regeneration in restoring bone defects using 'mesenchymal stromal cell' (MSC)-derived devitalized CMs in small and large animals. To scale up the size of treated defects using these CMs, we propose the introduction of a vascular supply. In this study, an arteriovenous (AV) loop was introduced as a vascular supply to devitalized 'MSCs'-derived CMs in a centimeter-scale porous chamber in rats. The extent of vascularization and remodeling was evaluated for chambers filled with CMs in the presence or absence of an AV loop at 4 and 8 weeks. While the AV loop's role in vascularization is established, our study uniquely shows that in a challenging <i>in vivo</i> setting with devitalized callus mimics, the AV loop was critical for initiating bone formation. Mineralization was observed in all groups <i>via</i> microCT, but bone tissue formed only in the AV loop group (50% of samples at 8 weeks), underscoring its influential role in supporting both vascular invasion and bone formation.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143149","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":"β3GALT2 Gene Promotes Osteogenic Differentiation of BMSCs on n-HA/PA66 Via Exosomes.","authors":"Lipeng Peng, Jian Yang, Linnan Wang, Qiujiang Li, Yueming Song","doi":"10.1089/ten.tea.2025.0013","DOIUrl":"https://doi.org/10.1089/ten.tea.2025.0013","url":null,"abstract":"<p><p>While β3GalT2 has been implicated in osteogenic regulation, its synergistic application with bioactive scaffolds remains unexplored. This study pioneers a dual-functional bone regeneration strategy by integrating β3GalT2-engineered bone marrow mesenchymal stem cells (BMSCs-β3GalT2) with nano-hydroxyapatite/polyamide 66 (n-HA/PA66) composites. First, we studied the effect of β3GalT2 on rat BMSCs (rBMSCs) by overexpression the β3GalT2 gene. Following this, we extracted exosomes and verified that β3GalT2 influences osteogenesis of rBMSCs through exosomes. Subsequently, we inoculated these rBMSCs on n-HA/PA66 and demonstrated the effects of β3GalT2 and n-HA/PA66 on osteogenic differentiation of rBMSCs. On this basis, we also explored the molecular mechanism of β3GalT2 regulating M1 polarization through exosomes. Finally, we verified our study by using animal models of skull defect and femur defect. Our results suggest that β3GalT2 promotes osteogenic differentiation of rBMSCs through exosomes. At the same time, rBMSCs-β3GalT2 combined with n-HA/PA66 showed good osteogenic effect <i>in vivo</i> and <i>in vitro</i>. In addition, we also found that β3GalT2 can regulate M1 polarization through exosomes. Our findings establish β3GalT2 as a master regulator of osteogenesis through cellular-exosomal-circuitry mechanisms. The biohybrid system synergistically combines gene-enhanced stem cells with tunable biomaterials, representing a paradigm shift in bone tissue engineering.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144417","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":"Donor Variability and 3D Culture Models Influence Human Mesenchymal Stem Cell Differentiation.","authors":"Sarah Jones, Michelle Tai, Manish Ayushman, Abena Peasah, Julia Johannsen, Fan Yang","doi":"10.1089/ten.tea.2025.0028","DOIUrl":"https://doi.org/10.1089/ten.tea.2025.0028","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) are widely used for tissue regeneration due to their multilineage differentiation potential and ability to secrete paracrine factors with immunomodulatory and angiogenic functions. Standard MSC differentiation protocols typically rely on two-dimensional (2D) or pellet culture models that are simple to use but not well-suited for translational or clinical applications. To promote better cell survival, tissue deposition, and differentiation of MSCs, a wide variety of three-dimensional (3D) biomaterial scaffolds and platforms have been developed that provide structural support and present a carefully defined set of biochemical and biophysical cues to cells. While biomaterials can guide cell behavior and promote desirable tissue regeneration outcomes, one remaining challenge in the field is inherent donor-to-donor variability in MSC behavior, phenotype, and differentiation capacity. Although MSCs are promising tools for regeneration, the influence of donor variability on MSC differentiation across culture models remains poorly understood. Previous studies typically use cells from a single donor or rely solely on standard culture models. To address these gaps, we compared MSCs from six human donors and assessed differentiation across chondrogenic, osteogenic, and adipogenic lineages using both standard (pellet or 2D) and 3D biomaterial-based culture models. Alginate hydrogels were used to assess chondrogenesis, while gelatin microribbon (µRB) hydrogels were used to evaluate osteogenesis and adipogenesis in 3D. Significant donor-to-donor variability was observed in differentiation outcomes across all three lineages and within both 2D and 3D culture models. By directly comparing donor variability in 2D and 3D, we provide evidence that standard 2D models cannot predict MSC differentiation capacity in 3D biomaterials. Therefore, to improve therapeutic efficacy and advance biomaterial-based strategies for tissue regeneration, it is critical to understand how donor variability affects MSC differentiation patterns across 3D biomaterial-based culture models.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129634","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":"Regenerative Potential of Human Umbilical Cord Vein for Urethral Reconstruction in Male Rabbit Model.","authors":"Clement Parat, Damien Carnicelli, Stephan Langonnet, Marc Sbizzera, Laurence Barnouin, Yao Chen, Laura Barrot, Paul Neuville, Nicolas Morel-Journel","doi":"10.1089/ten.tea.2025.0061","DOIUrl":"https://doi.org/10.1089/ten.tea.2025.0061","url":null,"abstract":"<p><p>Tissue engineering offers an alternative for augmentation urethroplasty; however, no ideal material has yet been developed. Recently, materials derived from amniotic tissues appear to exhibit promising properties. Herein, the aim of this study was to provide a proof of concept for the integration of the human umbilical cord vein for urethral reconstructions in rabbits. Rabbits were included in two groups; the control group underwent urethral reconstruction using autograft urethral tissue, and the test group received xenograft tissue (umbilical cord vein) after creating a 1 × 1 cm defect in the proximal urethra. At 3 weeks, endoscopy and biopsy were performed. At 6 weeks, the animals were euthanized, and their urethra and corpus cavernosum were sent for histopathological analysis. The six rabbits exhibited favorable clinical and endoscopic progress with no fistula or stenosis. Biopsy analysis found no lesion of the urothelium and chorion. Final histological analysis found similar results in both groups: normal histology with moderate urothelium vacuolation and a weak inflammatory cellular infiltrate. The present study provides a proof of concept of human umbilical cord vein as a scaffold for urethral regeneration. This could be an alternative to existing urethral tissue grafting procedures that can have difficulties with integration or immunological tolerance; however, further research is required.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129644","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":"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":"https://doi.org/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. Impact Statement In this study, poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) was modified with hyaluronic acid and kartogenin to synthesize a thermosensitive injectable hydrogel scaffold. The scaffold has anti-inflammatory and cartilage-promoting effects. This study used the scaffold to carry peripheral blood mesenchymal stem cells to repair cartilage defects in rabbit knee joints, providing a new idea for the treatment of cartilage defects.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-09","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}

{"title":"Effect of Microbial Stimuli and Bone Morphogenetic Protein 2 on Ectopic Bone Formation.","authors":"Nada Ristya Rahmani, Anneli Duits, Paree Khokhani, Michiel Croes, Vela Kaludjerovic, Debby Gawlitta, Harrie Weinans, Moyo C Kruyt","doi":"10.1089/ten.tea.2025.0020","DOIUrl":"https://doi.org/10.1089/ten.tea.2025.0020","url":null,"abstract":"<p><p>Advancements in biomaterials design increasingly focus on material-host immune interactions as one of the strategies to promote new bone formation, referred to as osteoimmunomodulation. Recent studies indicate that inflammatory stimuli can synergize with growth factors such as bone morphogenetic protein 2 (BMP-2) to promote bone formation. Pathogen-associated molecular patterns (PAMPs) are motifs expressed by microbes that are recognized by immune cells and induce an immune-stimulatory response. In this study, we combined PAMPs with low-dose BMP-2 on a biphasic calcium phosphate (BCP) scaffold and evaluated its effect on ectopic bone formation in a subcutaneous implantation model. The PAMPs tested include gamma-irradiated whole microbes (γi-<i>Staphylococcus aureus</i> and γi-<i>Candida albicans</i>), a vaccine (Bacillus Calmette-Guérin containing <i>Mycobacterium bovis</i>), bacterial cell wall components (peptidoglycan [PGN], lipopolysaccharide [LPS], lipoteichoic acid, and Pam3CysSerLys4), an exopolysaccharide (Curdlan), and nucleic acid analogues (polyinosinic:polycytidylic acid [Poly(I:C)] and Cytidine-phosphate-guanosine [CpG]-containing oligonucleotides type C). Implants consisting of BCP, PAMPs, and BMP-2 were placed subcutaneously in rabbits and evaluated for ectopic bone formation after 5 weeks. Implants with only BMP-2 served as controls. Of the PAMPs tested, only PGN and BMP-2 showed a positive bone volume compared with the control, with borderline significance (+4.4%, <i>p</i> = 0.08). Decreased bone volume was seen for LPS (-7.4%, <i>p</i> = 0.03) and Poly(I:C) (-6.3%, <i>p</i> = 0.04). Fluorochrome labeling at weeks 2 and 3 assessed mineralization onset, revealing no mineralization in the first 2 weeks and some implants showing onset at week 3. We observed variability in ectopic bone formation across animals, associated with higher osteoclast numbers in those where ectopic bone occurred versus those that did not (<i>p</i> = 0.004). PAMPs can modulate bone formation, but their effects are variable, requiring further refinement to harness their osteoimmunomodulatory properties effectively. Additionally, we highlight osteoclasts' important role in stimulating ectopic bone formation.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043435","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}