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.

Evaluation of Bi-Layer Silk Fibroin Grafts for Penile Tunica Albuginea Repair in a Rabbit Corporoplasty Model

The use of autologous tissue grafts for tunica albuginea repair in Peyronie’s disease and congenital chordee is often restricted by limited tissue availability and donor site morbidity, therefore new biomaterial options are needed. In this study, bi-layer silk fibroin (BLSF) scaffolds were investigated to support functional tissue regeneration of tunica albuginea in a rabbit corporoplasty model. Eighteen adult male, New Zealand white rabbits were randomized to nonsurgical controls (NSC, N = 3), or subjected to corporoplasty with BLSF grafts (N = 5); decellularized small intestinal submucosa (SIS) matrices (N = 5); or autologous tunica vaginalis (TV) flaps (N = 5). End-point evaluations were cavernosography, cavernosometry, histological, immunohistochemical, and histomorphometric assessments. Maximum intracorporal pressures (ICP) following papaverine-induced erection were similar between all groups. Eighty percent of rabbits repaired with BLSF scaffolds or TV flaps achieved full rigid erections, compared to 40% of SIS reconstructed animals. Five-minute peak erections were maintained in 60% of BLSF rabbits, compared to 20% of SIS and TV flap reconstructed rabbits. Graft perforation occurred in 60% of TV group at maximum ICP compared to 20% of BLSF cohort. Neotissues supported by SIS and BLSF scaffolds were composed of collagen type I and elastin fibers similar to NSC. SIS and TV flaps showed significantly elevated levels of corporal fibrosis relative to NSC with a corresponding decrease in corporal smooth muscle cells expressing contractile proteins. BLSF biomaterials represent emerging platforms for corporoplasty and produce superior functional and histological outcomes in comparison to TV flaps and SIS matrices for tunica albuginea repair.

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.