BioRN: Regeneration (Topic)最新文献

{"title":"Combining Sclerostin Neutralization with Tissue Engineering: An Improved Strategy for Craniofacial Bone Repair","authors":"Sophie Maillard, L. Sicard, Caroline Andrique, Coralie Torrens, J. Lesieur, B. Baroukh, T. Coradin, A. Poliard, L. Slimani, C. Chaussain","doi":"10.2139/ssrn.3919746","DOIUrl":"https://doi.org/10.2139/ssrn.3919746","url":null,"abstract":"Scaffolds associated with different types of mesenchymal stromal stem cells (MSC) are extensively studied for the development of novel therapies for large bone defects. Moreover, monoclonal antibodies have been recently introduced for the treatment of cancer-associated bone loss and other skeletal pathologies. In particular, antibodies against sclerostin, a key player in bone remodeling regulation, have demonstrated a real benefit for treating osteoporosis but their contribution to bone tissue-engineering remains uncharted. Here, we show that combining implantation of dense collagen hydrogels hosting wild-type (WT) murine dental pulp stem cells (mDPSC) with weekly systemic injections of a sclerostin antibody (Scl-Ab) leads to increased bone regeneration within critical size calvarial defects performed in WT mice. Furthermore, we show that bone formation is equivalent in calvarial defects in WT mice implanted with Sost knock-out (KO) mDPSC and in Sost KO mice, suggesting that the implantation of sclerostin-deficient MSC similarly promotes new bone formation than complete sclerostin deficiency. Altogether, our data demonstrate that an antibody-based therapy can potentialize tissue-engineering strategies for large craniofacial bone defects and urges the need to conduct research for antibody-enabled local inhibition of sclerostin. STATEMENT OF SIGNIFICANCE: : The use of monoclonal antibodies is nowadays broadly spread for the treatment of several conditions including skeletal bone diseases. However, their use to potentialize tissue engineering constructs for bone repair remains unmet. Here, we demonstrate that the neutralization of sclerostin, through either a systemic inhibition by a monoclonal antibody or the implantation of sclerostin-deficient mesenchymal stromal stem cells (MSC) directly within the defect, improves the outcome of a tissue engineering approach, combining dense collagen hydrogels and MSC derived from the dental pulp, for the treatment of large craniofacial bone defects.","PeriodicalId":262640,"journal":{"name":"BioRN: Regeneration (Topic)","volume":"112 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116455615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-Homing Strategies for in Situ Articular Cartilage Regeneration","authors":"Zhen Yang, Haojiang Li, Wei-hui Guo, Zhiguo Yuan, Liwei Fu, Shuangpeng Jiang, Cangjian Gao, Fuxin Wang, Kangkang Zha, Guangzhao Tian, Zhiqiang Sun, Bo Huang, Fu Wei, F. Cao, X. Sui, Shuyun Liu, Jiang Peng, Shibi Lu, Q. Guo","doi":"10.2139/ssrn.3568115","DOIUrl":"https://doi.org/10.2139/ssrn.3568115","url":null,"abstract":"Injuries to articular cartilage (AC) can lead to cartilage degeneration without timely and proper treatments and ultimately results in osteoarthritis. Regenerative medicine and tissue engineering techniques are emerging as promising approaches for AC regeneration and repair. Typically, AC regenerative medicine and tissue engineering can be divided into two categories, cell-based tissue engineering and cell-homing tissue engineering techniques, based on the involvement of seed cells. Although numerous cell-based techniques can regenerate and repair cartilage lesions to some extent, existing strategies are still restricted by limited cell sources, excessive costs, risks of disease transmission and complex manufacturing practices. However, cell-homing tissue engineering strategies avoid these drawbacks and offer great promise for in situ AC regeneration. These strategies rely on the recruitment of endogenous stem/progenitor cells, host tissue stimulation, and functional responses and thus can provide new insights into in situ cartilage regeneration. This review provides a brief overview of the status of cell-homing tissue engineering strategies; the subpopulations, distribution and migration routes of native joint-resident stem/progenitor cells for regenerating cartilage; chemoattractants that induce enhanced endogenous cell homing; and drug delivery systems and biofunctionalized scaffolds that are indispensable for facilitating in situ AC regeneration and repair.","PeriodicalId":262640,"journal":{"name":"BioRN: Regeneration (Topic)","volume":"8 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132817650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Ecm Patch Combines Human Fibroblast-Derived Matrix and Mesenchymal Stem Cells for Advanced Deep Wound Healing","authors":"S. Ha, E. Song, P. Du, M. Suhaeri, Jong Ho Lee, Kwideok Park","doi":"10.2139/ssrn.3545078","DOIUrl":"https://doi.org/10.2139/ssrn.3545078","url":null,"abstract":"Decellularized extracellular matrix (ECM)-based scaffold has been a very useful resource for effective tissue regeneration. In this study, we report a novel ECM patch that physically combines human fibroblast-derived matrix (hFDM) and polyvinyl alcohol (PVA) hydrogel. hFDM was obtained after decellularization of in vitro cultured human fibroblasts. We investigated the basic characteristics of hFDM itself using immunofluorescence (fibronectin, collagen type Ⅰ) and angiogenesis related factors analysis. Successful incorporation of hFDM with PVA produced an hFDM/PVA patch, which showed an excellent cytocompatibility with human mesenchymal stem cells (hMSCs), as assessed via cell adhesion, viability, and proliferation. Moreover, in vitro scratch assay using human dermal fibroblasts showed a significant improvement of cell migration when treated with the paracrine factors orignated from the hMSCs-incorporated hFDM. To evaluate therapeutic effect on wound healing, hMSCs were seeded on the hFDM/PVA patch and they were then transplanted into mouse full-thickness wound model. Among four experimental groups (control, PVA, hFDM/PVA, hMSC/hFDM/PVA), we found that hMSC/hFDM/PVA patch accelerated the wound closure with time. More notably, histology and immunofluorescence demonstrated that compared to normal skin tissue, hMSC/hFDM/PVA patch could lead to significantly advanced tissue regeneration, as confirmed via nearly normal epidermis thickness, skin adnexa regeneration (hair follicle), mature collagen deposition, and neovascularization. Additionally, cell tracking of pre-labelled hMSCs suggegsts the in vivo retention of transplanted cells in the wound region after transplantation of hMSC/hFDM/PVA patch. Taken together, our engineered ECM patch demonstrates a strong regeneration potential toward advanced wound healing.","PeriodicalId":262640,"journal":{"name":"BioRN: Regeneration (Topic)","volume":"24 3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114102286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silicon-Based Biomaterials Modulate the Adaptive Immune Response of T Lymphocytes to Promote Osteogenesis/Angiogenesis Via Epigenetic Regulation","authors":"Ting‐He Wu, Lei Chen, N. Ye, Runqing Fu, Lu Liu, Fei Yu, Xiaoting Wang, Jiang Chang, B. Fang, Chengtie Wu, L. Xia","doi":"10.2139/ssrn.3919725","DOIUrl":"https://doi.org/10.2139/ssrn.3919725","url":null,"abstract":"Silicon (Si)-based biomaterials have been widely applied for bone regeneration. However, the underlying mechanisms remain unknown. T lymphocyte-mediated adaptive immune response plays a vital role in the process of bone regeneration. In the present study, mesoporous silica (MS) was used as a model material of Si-based biomaterials. It showed that the supernatant of CD4 + T cells pretreated with MS extract significantly promoted the vascularized bone regeneration. The potential mechanism is closely related to the fact that MS extract could reduce the expression of regulatory factor X-1 (RFX-1) in CD4 + T cells, which could lead to interleukin-17A (IL-17A) overexpression through increased histone H3 acetylation and decreased DNA methylation and H3K9 trimethylation. Importantly, the in vivo experiments further revealed that MS particles dramatically stimulated bone regeneration with improved angiogenesis in the critical-sized calvarial defect mouse model accompanied by upregulation of IL-17A in peripheral blood and the proportion of Th17 cells.","PeriodicalId":262640,"journal":{"name":"BioRN: Regeneration (Topic)","volume":"6 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124752254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}