Engineering a cell-free bone regeneration platform using osteogenically primed MSC-EVs and nHAp-enriched IPN hydrogels.

IF 2.6 4区医学 Q4 CELL & TISSUE ENGINEERING

Regenerative medicine Pub Date : 2025-09-01 Epub Date: 2025-09-08 DOI:10.1080/17460751.2025.2557770

Ketki Holkar, Prasad Pethe, Vaijayanti Kale, Ganesh Ingavle

{"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":"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 in vitro 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 in vivo 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.","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}

引用次数: 0

Abstract

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 in vitro 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 in vivo 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.

查看原文本刊更多论文

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。

目的：本研究旨在通过将间充质干细胞来源的细胞外囊泡（MSC-EVs）整合到富含纳米羟基磷灰石（nHAp）的水凝胶支架中，增强其成骨潜能，用于骨再生应用。材料和方法：从naïve和成骨基质干细胞中分离出ev，并对其形态、载货量和细胞相容性进行表征。在3D互穿网络（IPN）水凝胶中使用MC3T3细胞体外评估它们的摄取和骨诱导活性。将最有效的EV配方加入到nHAp - IPN水凝胶支架中，并在体外和小鼠皮下植入模型中进行评估。结果：与大小和形态相当的naïve ev相比，引物的msc - ev显示出钙、ALP活性和成骨/血管生成mrna （Runx2, Vegf-a）的升高。两种类型的EV均能有效内化，无细胞毒性。与nHAp结合，引物ev增强了ALP活性、钙沉积和体内矿化。组织学分析证实支架生物相容性和矿化组织形成。结论：成骨诱导的msc - ev显著提高了基于nhap的水凝胶的成骨诱导性能，支持其作为骨组织工程无细胞治疗策略的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Regenerative medicine 医学-工程：生物医学

CiteScore

4.20

自引率

3.70%

发文量

审稿时长

6-12 weeks

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.