Nanostructured Tendon-Derived Scaffolds for Enhanced Bone Regeneration by Human Adipose-Derived Stem Cells

Abstract

Decellularized matrix-based scaffolds can induce enhanced tissue regeneration due to their biochemical, biophysical, and mechanical similarity to native tissues. In this study, we report a nanostructured decellularized tendon scaffold with aligned, nanofibrous structures to enhance osteogenic differentiation and in vivo bone formation of human adipose-derived stem cells (hADSCs). Using a bioskiving method, we prepared decellularized tendon scaffolds from tissue slices of bovine Achilles and neck tendons with or without fixation, and investigated the effects on physical and mechanical properties of decellularized tendon scaffolds, based on the types and concentrations of cross-linking agents. In general, we found that decellularized tendon scaffolds without fixative treatments were more effective in inducing osteogenic differentiation and mineralization of hADSCs in vitro. When non-cross-linked decellularized tendon scaffolds were applied together with hydroxyapatite for hADSC transplantation in critical-sized bone defects, they promoted bone-specific collagen deposition and mineralized bone formation 4 and 8 weeks after hADSC transplantation, compared to conventional collagen type I scaffolds. Interestingly, stacking of decellularized tendon scaffolds cultured with osteogenically committed hADSCs and those containing human cord blood-derived endothelial progenitor cells (hEPCs) induced vascularized bone regeneration in the defects 8 weeks after transplantation. Our study suggests that biomimetic nanostructured scaffolds made of decellularized tissue matrices can serve as functional tissue-engineering scaffolds for enhanced osteogenesis of stem cells.

Recent Advances in Scaffold Design and Material for Vascularized Tissue‐Engineered Bone Regeneration

“…Four groups were divided into no treatment, fibrin‐HA, collagen‐HA, and bovine neck tendon without fixation using glutaraldehyde (BAT‐NC)‐HA, and then adipose stem cells with scaffolds were transferred to a skull defect mouse model. After 8 weeks, bone formation in the defect was assessed by micro‐CT ( Figure A) . The results indicated that this composite can be an effective scaffold design for constructing vascularized tissue.…”

“…Mineralized bone formation in the defect was examined after 8 weeks. Reproduced with permission . Copyright 2016, American Chemical Society.…”

“…Some researchers have studied the mechanical properties and the biological properties of such decellularized scaffolds and found that they can promote and support the adhesion, growth, and osteogenic differentiation of human adipose‐derived stem cells (hADSC) and further enhance bone regeneration in a critical mouse bone defect model. Meanwhile the hADSC‐inoculated tendon scaffold and human endothelial progenitor cells inoculated in multiple layers of the tendon scaffold, resulting in a significant increase in bone regeneration in the vascular system, demonstrating an effective strategy for vascularized bone formation ( Figure A) . Around the same time, Mertsching and colleagues put forward a promising strategy of obtaining a vascularized stent material using decellularized intestinal segments that are harvested along with the vascular supply to produce tissue engineering scaffolds with native vascular networks.…”

“…A) Schematic illustration of the fabrication of nanofiber tendon‐derived scaffolds and the use of fabricated tendon scaffolds for hADSC transplantation in critical‐size skull defects. Reproduced with permission . Copyright 2016, American Chemical Society.…”

The Construction of Biomimetic Cementum Through a Combination of Bioskiving and Fluorine-Containing Biomineralization

“…Bioskiving, the technique combining sectioning, stacking, and rolling procedure, is a novel sectioning-based fabrication method (Alberti et al, 2014;Ghazanfari et al, 2019). Through bioskiving, decellularized tissue such as tendon could be processed into tendon-derived collagen scaffold (Dai et al, 2012;Ko et al, 2016). Since tendon is composed of type I collagen fiber with well-aligned structure, tendon-derived collagen sheet produced via sectioning process is characterized by highly parallel fibers.…”