Biomimetic porous scaffolds containing decellularized small intestinal submucosa and Sr2+/Fe3+ co-doped hydroxyapatite accelerate angiogenesis/osteogenesis for bone regeneration

The design of bone scaffolds is predominately aimed to well reproduce the natural bony environment by imitating the architecture/composition of host bone. Such biomimetic biomaterials are gaining increasing attention and acknowledged quite promising for bone tissue engineering. Herein, novel biomimetic bone scaffolds containing decellularized small intestinal submucosa matrix (SIS-ECM) and Sr2+/Fe3+ co-doped hydroxyapatite (SrFeHA) are fabricated for the first time by the sophisticated self-assembled mineralization procedure, followed by cross-linking and lyophilization post-treatments. The results indicate the constructed SIS/SrFeHA scaffolds are characterized by highly porous structures, rough microsurface and improved mechanical strength, as well as efficient releasing of bioactive Sr2+/Fe3+ and ECM components. These favorable physico-chemical properties endow SIS/SrFeHA scaffolds with an architectural/componential biomimetic bony environment which appears to be highly beneficial for inducing angiogenesis/osteogenesis both in vitro and in vivo. In particular, the cellular functionality and bioactivity of endotheliocytes/osteoblasts are significantly enhanced by SIS/SrFeHA scaffolds, and the cranial defects model further verifies the potent ability of SIS/SrFeHA to accelerate in vivo vascularization and bone regeneration following implantation. In this view these results highlight the considerable angiogenesis/osteogenesis potential of biomimetic porous SIS/SrFeHA scaffolds for inducing bone regeneration and thus may afford a new promising alternative for bone tissue engineering.

circPTP4A2-miR-330-5p-PDK2 Signaling Facilitates In Vivo Survival of HuMSCs on SF-SIS Scaffolds and Improves The Repair of Damaged Endometrium

Background Human umbilical cord MSCs (HuMSC)-based therapy has shown promising results in the treatment of intrauterine adhesions (lUA). In this study, our aim was to construct a HuMSC-seeded silk fibroin small-intestinal submucosa (SF-SIS) scaffold and evaluate the impact of repairing the damaged endometrium in an lUA mouse model. Methods To identify the functional effect of HuMSCs-silk cellulose (SF)- small-intestinal submucosa (SIS) scaffolds on the repair of damaged endometrium, a mouse lUA model was established in this study. The uterine morphology and fibrosis were evaluated by hematoxylin - eosin (H&E) staining and Masson staining. CircRNA sequencing, real-time PCR and RNA fluorescence in situ hybridization were used to screen and verify the potential circRNAs that involved in the repair of damaged endometrium by HuMSCs. Real time integrated cellular oxygen consumption rate (OCR) was measured using the Seahorse XF24 Extracellular Flux Analyser. The potential down-stream miRNAs and proteins of circRNAs were analyzed dual-luciferase report and Western Blot. Results We found that HuMSCs-SF-SIS not only increased the number of glands, but also reduced the ulcer area in the IUA model. Furthermore, we demonstrated that circPTP4A2 was elevated in the HuMSCs seeded on the SF-SIS scaffolds and stabilized the mitochondrial metabolism through miR-330-5p-PDK2 signaling, which contributes to endometrial repair progression. Conclusion In this study, we demonstrated that circPTP4A2 was elevated in the HuMSCs seeded on the SF-SIS scaffolds and stabilized the mitochondrial metabolism through miR-330-5p-PDK2 signaling, which contributes to endometrial repair progression. These findings demonstrate that HuMSC-seeded SF-SIS scaffolds are an encouraging method for the treatment of lUA.

Effects of hypoxia on Achilles tendon repair using adipose tissue-derived mesenchymal stem cells seeded small intestinal submucosa

Background The study was performed to evaluate the feasibility of utilizing small intestinal submucosa (SIS) scaffolds seeded with adipose-derived mesenchymal stem cells (ADMSCs) for engineered tendon repairing rat Achilles tendon defects and to compare the effects of preconditioning treatments (hypoxic vs. normoxic) on the tendon healing. Methods Fifty SD rats were randomized into five groups. Group A received sham operation (blank control). In other groups, the Achilles tendon was resected and filled with the original tendon (Group B, autograft), cell-free SIS (Group C), or SIS seeded with ADMSCs preconditioned under normoxic conditions (Group D) or hypoxic conditions (Group E). Samples were collected 4 weeks after operation and analyzed by histology, immunohistochemistry, and tensile testing. Results Histologically, compared with Groups C and D, Group E showed a significant improvement in extracellular matrix production and a higher compactness of collagen fibers. Group E also exhibited a significantly higher peak tensile load than Groups D and C. Additionally, Group D had a significantly higher peak load than Group C. Immunohistochemically, Group E exhibited a significantly higher percentage of MKX + cells than Group D. The proportion of ADMSCs simultaneously positive for both MKX and CM-Dil observed from Group E was also greater than that in Group D. Conclusions In this animal model, the engineered tendon grafts created by seeding ADMSCs on SIS were superior to cell-free SIS. The hypoxic precondition further improved the expression of tendon-related genes in the seeded cells and increased the rupture load after grafting in the Achilles tendon defects.