Mahnaz Babaahmadi, Behnoosh Tayebi, Nima Makvand Gholipour, Phillip Bendele, Jed Pheneger, Abolfazl Kheimeh, Amir Kamali, Mohammad Molazem, Hossein Baharvand, Mohamadreza Baghaban Eslaminejad, Ensiyeh Hajizadeh-Saffar, Seyedeh-Nafiseh Hassani
{"title":"Long-term passages of human clonal mesenchymal stromal cells can alleviate the disease in the rat model of collagen-induced arthritis resembling early passages of different heterogeneous cells","authors":"Mahnaz Babaahmadi, Behnoosh Tayebi, Nima Makvand Gholipour, Phillip Bendele, Jed Pheneger, Abolfazl Kheimeh, Amir Kamali, Mohammad Molazem, Hossein Baharvand, Mohamadreza Baghaban Eslaminejad, Ensiyeh Hajizadeh-Saffar, Seyedeh-Nafiseh Hassani","doi":"10.1002/term.3368","DOIUrl":"https://doi.org/10.1002/term.3368","url":null,"abstract":"<p>Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease of unknown cause. The interaction of immune system cells and the secretion of inflammatory cytokines with synovial cells leads to severe inflammation in the affected joints. Currently, medications, including non-steroidal anti-inflammatory drugs, glucocorticoids, and more recently, disease-modifying anti-rheumatic drugs, are used to reduce inflammation. However, long-term use of these drugs causes adverse effects or resistance in a considerable number of RA patients. Recent findings revealed the safety and efficacy of mesenchymal stromal cells (MSCs)-based therapies both in RA animal models and clinical trials. Here, the beneficial effects of bone marrow-derived heterogeneous MSCs (BM-hMSCs) and Wharton jelly-derived MSCs (WJ-MSCs) at early passages were compared to BM-derived clonal MSCs (BM-cMSCs) at high passage number on a rat model of collagen-induced arthritis. Results showed that systemic delivery of MSCs significantly reversed adverse changes in body weight, paw swelling, and arthritis score in all MSC-treated groups. Radiological images and histological evaluation demonstrated the therapeutic effects of MSCs. There was a decrease in serum level of anti-collagen type II immunoglobulin G and the inflammatory cytokines interleukin (IL)-1β, IL-6, IL-17, and tumor necrosis factor-α in all MSC-treated groups. In contrast, an increase in inhibitory cytokines transforming growth factor-β and IL-10 was seen. Notably, the long-term passages of BM-cMSCs could alleviate RA symptoms similar to the early passages of WJ-MSCs and BM-hMSCs. The importance of BM-cMSCs is the potential to establish cell banks with billions of cells derived from a single donor that could be a competitive cell-based therapy to treat RA.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 12","pages":"1261-1275"},"PeriodicalIF":3.3,"publicationDate":"2022-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5828867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effect of amniotic membrane and platelet-rich fibrin membrane on bone healing post endodontic surgery: An ultrasonographic, randomized controlled study","authors":"Saumya Johri, Promila Verma, Aseem Prakash Tikku, Rhythm Bains, Neera Kohli","doi":"10.1002/term.3362","DOIUrl":"https://doi.org/10.1002/term.3362","url":null,"abstract":"<p>The use of membrane barriers and bone grafting materials in endodontic surgery promotes healing by regeneration rather than repair by scar tissue. Due to its valuable regenerative and therapeutic properties, the human amniotic membrane can support ideal periapical rehabilitation and promote better healing after surgery. The current trial aimed to evaluate the amniotic membrane's healing potential and compare it with platelet-rich fibrin using color doppler sonography. The current study is a randomized, double-blinded, parallel-group, single-center study. Thirty-four systematically healthy individuals requiring endodontic surgery who fulfilled all inclusion and exclusion criteria were selected and randomly placed in two groups. Surgical curettage of the bony lesion was performed and filled with hydroxyapatite graft. Amniotic membrane (Group 1) and platelet-rich fibrin (Group 2) were placed over the bony crypt, and the flap was sutured back. The lesion's surface area and vascularity were the parameters assessed with ultrasound and color doppler. and observations: The groups found a significant difference in mean vascularity at 1 month and mean vascularity change from baseline to 1 month (<i>p</i> < 0.05). Mean surface area had no statistically significant difference between the groups. However, in terms of the percentage change in surface area, a significant difference was found from baseline to 6 months (<i>p</i> < 0.05). Amniotic membrane was a significantly better promoter of angiogenesis than platelet-rich fibrin in the current trial. The osteogenic potential of both materials was similar. However, the clinical application, availability, and cost-effectiveness of amniotic membrane support it as a promising therapeutic alternative in clinical translation. Further large-scale trials and histologic studies are warranted.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 12","pages":"1208-1222"},"PeriodicalIF":3.3,"publicationDate":"2022-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5935876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evolution of functional tissue engineering for tendon and ligament repair","authors":"David L. Butler","doi":"10.1002/term.3360","DOIUrl":"https://doi.org/10.1002/term.3360","url":null,"abstract":"<p>This review paper is motivated by a Back-to-Basics presentation given by the author at the 2022 Orthopaedic Research Society meeting in Tampa, Florida. I was tasked with providing a brief history of research leading up to the introduction of functional tissue engineering (FTE) for tendon and ligament repair. Beginning in the 1970s, this timeline focused on two common orthopedic soft tissue problems, anterior cruciate ligament ruptures in the knee and supraspinatus tendon injuries in the shoulder. Historic changes in the field over the next 5 decades revealed a transformation from a focus more on mechanics (called “bioMECHANICS”) on a larger (tissue) scale to a more recent focus on biology (called “mechanoBIOLOGY”) on a smaller (cellular and molecular) scale. Early studies by surgeons and engineers revealed the importance of testing conditions for ligaments and tendons (e.g., high strain rates while avoiding subject disuse and immobility) and the need to measure in vivo forces in these tissues. But any true tissue engineering and regeneration in these early decades was limited more to the use of auto-, allo- and xenografts than actual generation of stimulated cell-scaffold constructs in culture. It was only after the discovery of tissue engineering in 1988 and the recognition of frequent rotator cuff injuries in the early 1990s, that biologists joined surgeons and engineers to discover mechanical and biological testing criteria for FTE. This review emphasizes the need for broader and more inclusive collaborations by surgeons, biologists and engineers in the short term with involvement of those in biomaterials, manufacturing, and regulation of new products in the longer term.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 12","pages":"1091-1108"},"PeriodicalIF":3.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5691448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recent advances in gene therapy for bone tissue engineering","authors":"Fatemeh Ranjbarnejad, Mozafar Khazaei, Alireza Shahryari, Fatemeh Khazaei, Leila Rezakhani","doi":"10.1002/term.3363","DOIUrl":"https://doi.org/10.1002/term.3363","url":null,"abstract":"<p>Autografting, a major treatment for bone fractures, has potential risks related to the required surgery and disease transmission. Bone morphogenetic proteins (BMPs) are the most common osteogenic factors used for bone-healing applications. However, BMP delivery can have shortcomings such as a short half-life and the high cost of manufacturing the recombinant proteins. Gene delivery methods have demonstrated promising alternative strategies for producing BMPs or other osteogenic factors using engineered cells. These approaches can also enable temporal overexpression and local production of the therapeutic genes in the target tissues. This review addresses recent progress on engineered viral, non-viral, and RNA-mediated gene delivery systems that are being used for bone repair and regeneration. Advances in clustered regularly interspaced short palindromic repeats/Cas9 genome engineering for bone tissue regeneration also is discussed.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 12","pages":"1121-1137"},"PeriodicalIF":3.3,"publicationDate":"2022-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6171617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Piotr Sass, Pawe? Sosnowski, Jolanta Kamińska, Milena Deptu?a, Aneta Skoniecka, Jacek Zieliński, Sylwia Rodziewicz-Motowid?o, Micha? Piku?a, Pawe? Sachadyn
{"title":"Examination of epigenetic inhibitor zebularine in treatment of skin wounds in healthy and diabetic mice","authors":"Piotr Sass, Pawe? Sosnowski, Jolanta Kamińska, Milena Deptu?a, Aneta Skoniecka, Jacek Zieliński, Sylwia Rodziewicz-Motowid?o, Micha? Piku?a, Pawe? Sachadyn","doi":"10.1002/term.3365","DOIUrl":"https://doi.org/10.1002/term.3365","url":null,"abstract":"<p>DNA methyltransferase inhibitor zebularine was proven to induce regeneration in the ear pinna in mice. We utilized a dorsal skin wound model to further evaluate this epigenetic inhibitor in wound healing. Full-thickness excisional wounds were made on the dorsum of 2 and 10-month-old healthy BALB/c and 3 and 8-month-old diabetic (db/db) mice, followed by topical or intraperitoneal zebularine delivery. Depending on the strain, age, dose, and delivery, the zebularine treatments either had no effect or accelerated or delayed wound closure. In principle, zebularine applied topically moderately promoted wound closure in the healthy but markedly delayed in the diabetic mice, which was in line with decreased viability of cultured keratinocytes from diabetic patients exposed to zebularine. The histological analysis revealed an improvement in the architecture of restored skin in zebularine-treated mice, manifested as a distinct layered pattern resembling <i>panniculus carnosus</i>. The finding corresponds with the zebularine-mediated activation of the <i>Wnt5a</i> gene, an essential regulator of Wnt signaling, the pathway involved in hair follicle development, the process which in turn is connected with regenerative skin healing. Although zebularine did not remarkably accelerate wound healing, zebularine and other epigenetic inhibitors deserve further testing as potential drugs to improve the quality of restored skin.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 12","pages":"1238-1248"},"PeriodicalIF":3.3,"publicationDate":"2022-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/term.3365","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6174257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exosomal let-7f-5p derived from mineralized osteoblasts promotes the angiogenesis of endothelial cells via the DUSP1/Erk1/2 signaling pathway","authors":"Yiqun He, Hailong Li, Zuochong Yu, Linli Li, Xujun Chen, Aolei Yang, Feizhou Lyu, Youhai Dong","doi":"10.1002/term.3358","DOIUrl":"https://doi.org/10.1002/term.3358","url":null,"abstract":"<p>Blood vessel formation is the prerequisite for the survival and growth of tissue-engineered bone. Mineralized osteoblasts (MOBs) have been shown to regulate angiogenesis through the secretion of exosomes containing various pro-angiogenic factors. However, whether the mineralized osteoblast-derived exosomes (MOB-Exos) containing let-7f-5p can regulate the angiogenesis of endothelial cells (ECs) is still unknown. In this study, the angiogenic capabilities of ECs respectively treated with MOB-Exos, let-7f-5p mimicked MOB-Exos (miR mimic group), and let-7f-5p inhibited MOB-Exos (miR inhibitor group) were compared through in vitro and in vivo studies. Moreover, the potential mechanism of MOB-Exo let-7f-5p regulating angiogenesis was explored by verifying the role of the Erk1/2 signaling pathway and target gene DUSP1. The results showed that MOB-Exos could significantly promote the angiogenesis of ECs, which could be enhanced by mimicked exosomal let-7f-5p and attenuated by inhibited exosomal let-7f-5p. Let-7f-5p could suppress the luciferase activity of wide-type DUSP1, and the mutation of DUSP1 could abrogate the repressive ability of let-7f-5p. Furthermore, the expression of DUSP1 exhibited a reversed trend to that of pErk1/2. The expression of pErk1/2 was significantly higher in the miR mimic group and lower in the miR inhibitor group than that in the MOB-Exos group, while inhibition of pErk1/2 could partly impair the angiogenic capabilities of ECs. In conclusion, we concluded that exosomal let-7f-5p derived from MOBs could promote the angiogenesis of ECs via activating the DUSP1/Erk1/2 signaling pathway, which might be a promising target for promoting the angiogenesis of tissue-engineered bone.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 12","pages":"1184-1195"},"PeriodicalIF":3.3,"publicationDate":"2022-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6049484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effective decellularization of human skin tissue for regenerative medicine by supercritical carbon dioxide technique","authors":"Nguyen Ngan Giang, Xuan-Tung Trinh, Jeonghun Han, Pham Ngoc Chien, Jua Lee, Seong-Rae Noh, Yongwoo Shin, Sun-Young Nam, Chan-Yeong Heo","doi":"10.1002/term.3359","DOIUrl":"https://doi.org/10.1002/term.3359","url":null,"abstract":"<p>Allotransplantation, performed using an acellular dermal matrix (ADM), plays a significant role in the cultivation of constituted and damaged organs in clinical. Herein, we fabricated an innovative ADM for allografting derived from decellularized human skin by utilizing the supercritical fluid of carbon dioxide to eliminate immunogenic components. By using histological staining, the ADM product demonstrated the successful removal of cellular constituents without exerting any harmful influence on the extracellular matrix. The results from DNA electrophoresis also supported this phenomenon by showing the complete DNA removal in the product, accompanied by the absence of Major Histocompatibility Complex 1, which suggested the supercritical fluid is an effective method for cellular withdrawal. Moreover, the mechanical property of the ADM products, which showed similarity to that of native skin, displayed great compatibility for using our human-derived ADM as an allograft in clinical treatment. Specifically, the cell viability demonstrated the remarkable biocompatibility of the product to human bio-cellular environment which was noticeably higher than that of other products. Additionally, the significant increase in the level of growth factors such as vascular endothelial growth factor, urokinase-type plasminogen activator receptor, granulocyte-macrophage colony-stimulating factor suggested the ability to stimulate cellular processes, proving the products to be innovative in the field of regeneration when applied to clinical in the future. This study provides a thoroughly extensive analysis of the new ADM products, enabling them to be applied in industrial and clinical treatment.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 12","pages":"1196-1207"},"PeriodicalIF":3.3,"publicationDate":"2022-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6158248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kyle Sylakowski, Peter Hwang, Amritha Justin, Hanshuang Shao, Diana Whaley, Yadong Wang, Alan Wells
{"title":"Matricellular protein Tenascin-C enhances mesenchymal stem cell angiogenic and wound healing efficacy under ischemic conditions","authors":"Kyle Sylakowski, Peter Hwang, Amritha Justin, Hanshuang Shao, Diana Whaley, Yadong Wang, Alan Wells","doi":"10.1002/term.3367","DOIUrl":"https://doi.org/10.1002/term.3367","url":null,"abstract":"<p>Human mesenchymal stem cells/multipotent stromal cells (MSCs) hold great promise in aiding wound healing through their ability to modulate all phases of repair and regeneration, most notably their secretion of pro-regenerative paracrine factors. However, MSC clinical utility is hindered by poor survival rates post-transplantation due to the harsh microenvironment in injured tissue. Previous work has shown that the matricellular protein Tenascin-C (TNC) provides survival signaling to MSCs via the epidermal growth factor receptor by restricting its activation at the plasma membrane, resulting in enhanced prosurvival signals. Herein, we investigate how TNC influences MSC survival and MSC-mediated promotion of the wound healing process. This study examined the survival and angiogenic potential of MSCs cultured on TNC-coated surfaces under ischemic duress in vitro. We also assessed the angiogenic and wound healing outcomes of MSC + TNC in vivo using a CXCR3−/− mouse model that exhibits a delayed healing phenotype within the tissue replacement phase of repair. We found that MSCs in the presence of TNC exhibit higher levels of angiogenic-promoting processes, collagen maturation, and an overall better wound healing outcome than MSCs administered alone. This was seen in vitro in terms of enhanced tube formation. In vivo, the MSCs in the presence of TNC stabilized with a coacervate delivery system resulted in more regenerative wounds with accelerated maturation of the dermis. These findings suggest the coupling of TNC to MSCs as a promising tool for future MSC-ECM combinatorial therapies for wound healing applications.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 12","pages":"1249-1260"},"PeriodicalIF":3.3,"publicationDate":"2022-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6050434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jijo Wilson, V. G. Rahul, Lynda V. Thomas, Prabha D. Nair
{"title":"Three-dimensional wet electrospun scaffold system for the differentiation of adipose-derived mesenchymal stem cells to islet-like clusters","authors":"Jijo Wilson, V. G. Rahul, Lynda V. Thomas, Prabha D. Nair","doi":"10.1002/term.3366","DOIUrl":"https://doi.org/10.1002/term.3366","url":null,"abstract":"<p>Stem cell-derived islet-like clusters (ILCs) are an alternative source of pancreatic beta cells for the treatment of diabetic mellitus. An ideal 3D culture platform for the generation of ILCs of desired cluster size is a challenge due to the clustering of islet cells in the 2D culture systems. The islet cells cultured in 2D conditions produce clusters of large size, which are less efficient in terms of insulin secretion and viability. In this study, we report that ILCs formed on a PCL-based wet electrospun fibrous scaffold with larger pore size produced clusters of the desired size, compared to that cultured on a conventional electrospun sheet. The collagen functionalization on this wet electrospun polycaprolactone (PCL) scaffold showed enhanced insulin secretion and cell viability compared to the non-functionalized or conventionally electrospun PCL scaffold. The collagen-coated wet electrospun 3D scaffold produced ILCs of cluster diameter 70 ± 20 μm and the conventionally electrospun PCL sheet produced larger ILC clusters of diameter 300 ± 10 μm. Hence the results indicate the collagen-functionalized wet electrospun scaffold system could be a potential scaffold for islet tissue engineering.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 12","pages":"1276-1283"},"PeriodicalIF":3.3,"publicationDate":"2022-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6145522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zecheng Li, Shi Cheng, Ang Li, Chengchao Song, Anlong Jiang, Fangxing Xu, Hui Chi, Jinglong Yan, Guanghua Chen
{"title":"Fabrication of BMP-2-peptide–Deferoxamine- and QK-peptide-functionalized nanoscaffolds and their application for bone defect treatment","authors":"Zecheng Li, Shi Cheng, Ang Li, Chengchao Song, Anlong Jiang, Fangxing Xu, Hui Chi, Jinglong Yan, Guanghua Chen","doi":"10.1002/term.3364","DOIUrl":"https://doi.org/10.1002/term.3364","url":null,"abstract":"<p>The microenvironment in the healing process of large bone defects requires suitable conditions to promote osteogenesis and angiogenesis. Coaxial electrospinning is a mature method in bone tissue engineering (BTE) and allows functional modification. Appropriate modification methods can be used to improve the bioactivity of scaffolds for BTE. In this study, coaxial electrospinning with QK peptide (a Vascular endothelial growth factor mimetic peptide) and BMP-2 peptide–DFO (BD) was performed to produce double-modified PQBD scaffolds with vascularizing and osteogenic features. The morphology of coaxially electrospun scaffolds was verified by scanning electron microscopy (SEM) and transmission electron microscopy. Laser scanning confocal microscopy and Fourier transform infrared spectroscopy confirmed that BD covalently bound to the surface of the P and PQ scaffolds. In vitro, the PQBD scaffold promoted the adhesion and proliferation of bone marrow stromal cells (BMSCs). Both QK peptide and BD showed sustainable release and preservation of biological activity, enhancing the osteogenic differentiation of BMSCs and the migration of human umbilical vein endothelial cells and promoting angiogenesis. The combined ability of these factors to promote osteogenesis and angiogenesis is superior to that of each alone. In vivo, the PQBD scaffold was implanted into the bone defect, and after 8 weeks, the defect area was almost completely covered by new bone tissue. Histology showed more mature bone tissue and more blood vessels. PQBD scaffolds promote both angiogenesis and osteogenesis, offering a promising approach to enhance bone regeneration in the treatment of large bone defects.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"16 12","pages":"1223-1237"},"PeriodicalIF":3.3,"publicationDate":"2022-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6158256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}