Hierarchically Demineralized Cortical Bone Combined With Stem Cell–Derived Extracellular Matrix for Regeneration of the Tendon-Bone Interface

Hwang

Front. Bioeng. Biotechnol.

et al. 2022

The mammalian tissue extracellular matrix (ECM) has been used as a scaffold to facilitate the repair and reconstruction of numerous tissues. However, the material properties of decellularized ECM (dECM) from in vitro cell cultures and the effect of these properties on wound remodeling remain unclear. To elucidate its biological activity, we extracted dECM from human lung fibroblasts, fabricated it into a patch, and applied it to a full-thickness skin wound. The fibroblast-derived dECM (fdECM) maintained the content of collagen Ⅰ, collagen Ⅳ, and elastin, and the extraction process did not damage its critical growth factors. The fdECM-conjugated collagen patch (COL-fdECM) facilitated wound contraction and angiogenesis in the proliferative phase when applied to the in vivo full-thickness skin wound model. Moreover, the COL-fdECM treated wound showed increased regeneration of the epidermal barrier function, mature collagen, hair follicle, and subepidermal nerve plexus, suggesting qualitative skin remodeling. This therapeutic efficacy was similarly observed when applied to the diabetic ulcer model. fdECM was shown to help remodel the tissue by regulating fibroblast growth factors, matrix metalloproteinases, and tissue inhibitors of metalloproteinases via the p38 and ERK signaling pathways in an in vitro experiment for understanding the underlying mechanism. These results provide a biological basis for cell-derived ECM as a multi-functional biomaterial applicable to various diseases.

Section: Introductionmentioning

confidence: 99%

Effect of Decellularized Extracellular Matrix Bioscaffolds Derived from Fibroblasts on Skin Wound Healing and Remodeling

Hwang

Front. Bioeng. Biotechnol.

et al. 2022

“…Recently, biological grafts based on tissue engineering strategies have offered a novel alternative approach for the treatment of RCT injury. 3 Graft materials—including synthetic materials and extracellular matrix scaffolds, such as acellular dermal matrix, 18 small intestinal submucosa, 6 demineralized bone matrix, 15,31 and ovine forestomach matrix 28 —have been used to repair RCT tears to improve the rate and quality of biological healing.…”

mentioning

confidence: 99%

Decellularized Human Umbilical Cord Wharton Jelly Scaffold Improves Tendon Regeneration in a Rabbit Rotator Cuff Tendon Defect Model

et al. 2021

Background: Owing to limited self-healing capacity, failure of rotator cuff tendon healing is a common complication after surgery. Biological scaffolds have garnered attention owing to their potential to enhance healing outcomes. Purpose: To verify the effect of the decellularized umbilical cord Wharton jelly (DUCWJ) scaffold as a bridging scaffold in a rabbit model of acute rotator cuff tendon defect. Study Design: Controlled laboratory study. Methods: We fabricated a DUCWJ scaffold using a physicochemical decellularized method, evaluating changes in the umbilical cord Wharton jelly before and after decellularization. Scanning electron microscopy and biomechanical testing were performed to determine the microstructure and mechanical properties. We assessed cytocompatibility and cell regulatory behavior of the scaffold toward tendon stem/progenitor cells (TSPCs). A supraspinatus tendon defect was created in 54 New Zealand White rabbits, allocated to the DUCWJ scaffold repair group and the negative control group (without scaffold). Histology, reverse transcription polymerase chain reaction, and biomechanical tensile strength were assessed at 4, 8, and 12 weeks postoperatively. Results: Decellularization completely removed cells from the umbilical cord Wharton jelly, retained a considerable amount of glycosaminoglycan and collagen, and preserved the microstructure and tensile strength. The DUCWJ scaffold facilitated migration and proliferation of TSPCs in vitro. Tendon-related gene expression revealed that the DUCWJ scaffold could maintain the tenocyte phenotype of TSPCs. In the in vivo study, the DUCWJ scaffold improved tendon healing and enhanced the biomechanical strength of repaired tendons. Histological evaluation scores of the DUCWJ group were significantly higher than those of the negative control at 4, 8, and 12 weeks after surgery ( P < .05). In repaired tendon tissues, reverse transcription polymerase chain reaction findings revealed that the DUCWJ scaffold stimulated tendon development and maturation. Furthermore, an overall increase in ultimate load and tensile modulus was noted over time; the DUCWJ group presented better results than the negative control group ( P < .05). Conclusion: The DUCWJ scaffold has an excellent 3-dimensional porous structure, good biocompatibility, and fundamental biomechanical characteristics, and it promotes migration, attachment, and proliferation of TSPCs. The in vivo animal study demonstrated that the DUCWJ scaffold has potential for tendon regeneration in an acute rotator cuff tendon defect model Clinical Relevance: DUCWJ scaffolds have potential as a regenerative material to augment rotator cuff healing in the clinical setting.

“…The significant genes are listed in Table 2 and Fig. 3 E. We found that the expression of mineralization markers such as BGN, COL11A1 , and COL10A1 were significantly increased [ [30] , [31] , [32] , [33] ]. Similarly, the expression of vascular and neurological differentiation markers such as COL8A2 and ANKRD1 also increased to a certain extent [ 34 , 35 ].…”

Section: Resultsmentioning

confidence: 99%

“…Conversely, other studies have shown that the Wnt/β-catenin signaling pathway can promote the odontogenic differentiation of the hDPSCs. The importance of β-catenin has been revealed in several studies [ [30] , [31] , [32] ]. β-catenin is strongly expressed in odontoblasts and is necessary for root formation [ 26 , [27] , [44] ].…”

Section: Discussionmentioning

confidence: 99%

Treated dentin matrix induces odontogenic differentiation of dental pulp stem cells via regulation of Wnt/β-catenin signaling

Liu

Sun

Yuan

et al. 2022

Bioactive Materials

Treated dentin matrix (TDM) is an ideal scaffold material containing multiple extracellular matrix factors. The canonical Wnt signaling pathway is necessary for tooth regeneration. Thus, this study investigated whether the TDM can promote the odontogenic differentiation of human dental pulp stem cells (hDPSCs) and determined the potential role of Wnt/β-catenin signaling in this process. Different concentrations of TDM promoted the dental differentiation of the hDPSCs and meanwhile, the expression of GSK3β was decreased. Of note, the expression of the Wnt/β-catenin pathway-related genes changed significantly in the context of TDM induction, as per RNA sequencing (RNA seq) data. In addition, the experiment showed that new dentin was visible in rat mandible cultured with TDM, and the thickness was significantly thicker than that of the control group. In addition, immunohistochemical staining showed lower GSK3β expression in new dentin. Consistently, the GSK3β knockdown hDPSCs performed enhanced odotogenesis compared with the control groups. However, GSK3β overexpressing could decrease odotogenesis of TDM-induced hDPSCs. These results were confirmed in immunodeficient mice and Wistar rats. These suggest that TDM promotes odontogenic differentiation of hDPSCs by directly targeting GSK3β and activating the canonical Wnt/β-catenin signaling pathway and provide a theoretical basis for tooth regeneration engineering.