{"title":"利用成骨引物msc - ev和富含nhap的IPN水凝胶构建无细胞骨再生平台。","authors":"Ketki Holkar, Prasad Pethe, Vaijayanti Kale, Ganesh Ingavle","doi":"10.1080/17460751.2025.2557770","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to enhance the osteoinductive potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) by integrating them into a nano-hydroxyapatite (nHAp)-enriched hydrogel scaffold for bone regeneration applications.</p><p><strong>Materials & methods: </strong>EVs were isolated from naïve and osteogenically primed MSCs and characterized for morphology, cargo content, and cytocompatibility. Their uptake and osteoinductive activity were assessed <i>in</i> <i>vitro</i> using MC3T3 cells within a 3D interpenetrating network (IPN) hydrogel. The most effective EV formulation was incorporated into an nHAp - IPN hydrogel scaffold and evaluated both in vitro and in a murine subcutaneous implantation model.</p><p><strong>Results: </strong>Primed MSC-EVs showed elevated calcium, ALP activity, and osteogenic/angiogenic mRNAs (<i>Runx2</i>, <i>Vegf-a</i>) compared to naïve EVs, with comparable size and morphology. Both EV types were internalized efficiently without cytotoxicity. In combination with nHAp, primed EVs enhanced ALP activity, calcium deposition, and <i>in</i> <i>vivo</i> mineralization. Histological analysis confirmed scaffold biocompatibility and mineralized tissue formation.</p><p><strong>Conclusions: </strong>Osteogenically primed MSC-EVs significantly improved the osteoinductive performance of nHAp-based hydrogels, supporting their potential as a cell-free therapeutic strategy for bone tissue engineering.</p>","PeriodicalId":21043,"journal":{"name":"Regenerative medicine","volume":" ","pages":"375-386"},"PeriodicalIF":2.6000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502811/pdf/","citationCount":"0","resultStr":"{\"title\":\"Engineering a cell-free bone regeneration platform using osteogenically primed MSC-EVs and nHAp-enriched IPN hydrogels.\",\"authors\":\"Ketki Holkar, Prasad Pethe, Vaijayanti Kale, Ganesh Ingavle\",\"doi\":\"10.1080/17460751.2025.2557770\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aims: </strong>This study aimed to enhance the osteoinductive potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) by integrating them into a nano-hydroxyapatite (nHAp)-enriched hydrogel scaffold for bone regeneration applications.</p><p><strong>Materials & methods: </strong>EVs were isolated from naïve and osteogenically primed MSCs and characterized for morphology, cargo content, and cytocompatibility. Their uptake and osteoinductive activity were assessed <i>in</i> <i>vitro</i> using MC3T3 cells within a 3D interpenetrating network (IPN) hydrogel. The most effective EV formulation was incorporated into an nHAp - IPN hydrogel scaffold and evaluated both in vitro and in a murine subcutaneous implantation model.</p><p><strong>Results: </strong>Primed MSC-EVs showed elevated calcium, ALP activity, and osteogenic/angiogenic mRNAs (<i>Runx2</i>, <i>Vegf-a</i>) compared to naïve EVs, with comparable size and morphology. Both EV types were internalized efficiently without cytotoxicity. In combination with nHAp, primed EVs enhanced ALP activity, calcium deposition, and <i>in</i> <i>vivo</i> mineralization. Histological analysis confirmed scaffold biocompatibility and mineralized tissue formation.</p><p><strong>Conclusions: </strong>Osteogenically primed MSC-EVs significantly improved the osteoinductive performance of nHAp-based hydrogels, supporting their potential as a cell-free therapeutic strategy for bone tissue engineering.</p>\",\"PeriodicalId\":21043,\"journal\":{\"name\":\"Regenerative medicine\",\"volume\":\" \",\"pages\":\"375-386\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502811/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Regenerative medicine\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.1080/17460751.2025.2557770\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/9/8 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"CELL & TISSUE ENGINEERING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Regenerative medicine","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1080/17460751.2025.2557770","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/9/8 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
Engineering a cell-free bone regeneration platform using osteogenically primed MSC-EVs and nHAp-enriched IPN hydrogels.
Aims: This study aimed to enhance the osteoinductive potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) by integrating them into a nano-hydroxyapatite (nHAp)-enriched hydrogel scaffold for bone regeneration applications.
Materials & methods: EVs were isolated from naïve and osteogenically primed MSCs and characterized for morphology, cargo content, and cytocompatibility. Their uptake and osteoinductive activity were assessed invitro using MC3T3 cells within a 3D interpenetrating network (IPN) hydrogel. The most effective EV formulation was incorporated into an nHAp - IPN hydrogel scaffold and evaluated both in vitro and in a murine subcutaneous implantation model.
Results: Primed MSC-EVs showed elevated calcium, ALP activity, and osteogenic/angiogenic mRNAs (Runx2, Vegf-a) compared to naïve EVs, with comparable size and morphology. Both EV types were internalized efficiently without cytotoxicity. In combination with nHAp, primed EVs enhanced ALP activity, calcium deposition, and invivo mineralization. Histological analysis confirmed scaffold biocompatibility and mineralized tissue formation.
Conclusions: Osteogenically primed MSC-EVs significantly improved the osteoinductive performance of nHAp-based hydrogels, supporting their potential as a cell-free therapeutic strategy for bone tissue engineering.
期刊介绍：
Regenerative medicine replaces or regenerates human cells, tissue or organs, to restore or establish normal function*. Since 2006, Regenerative Medicine has been at the forefront of publishing the very best papers and reviews covering the entire regenerative medicine sector. The journal focusses on the entire spectrum of approaches to regenerative medicine, including small molecule drugs, biologics, biomaterials and tissue engineering, and cell and gene therapies – it’s all about regeneration and not a specific platform technology. The journal’s scope encompasses all aspects of the sector ranging from discovery research, through to clinical development, through to commercialization. Regenerative Medicine uniquely supports this important area of biomedical science and healthcare by providing a peer-reviewed journal totally committed to publishing the very best regenerative medicine research, clinical translation and commercialization.
Regenerative Medicine provides a specialist forum to address the important challenges and advances in regenerative medicine, delivering this essential information in concise, clear and attractive article formats – vital to a rapidly growing, multidisciplinary and increasingly time-constrained community.
Despite substantial developments in our knowledge and understanding of regeneration, the field is still in its infancy. However, progress is accelerating. The next few decades will see the discovery and development of transformative therapies for patients, and in some cases, even cures. Regenerative Medicine will continue to provide a critical overview of these advances as they progress, undergo clinical trials, and eventually become mainstream medicine.
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