Mesenchymal Stem Cells–Hydrogel Microspheres System for Bone Regeneration in Calvarial Defects

Abstract

The repair of large bone defects in clinic is a challenge and urgently needs to be solved. Tissue engineering is a promising therapeutic strategy for bone defect repair. In this study, hydrogel microspheres (HMs) were fabricated to act as carriers for bone marrow mesenchymal stem cells (BMSCs) to adhere and proliferate. The HMs were produced by a microfluidic system based on light-induced gelatin of gelatin methacrylate (GelMA). The HMs were demonstrated to be biocompatible and non-cytotoxic to stem cells. More importantly, the HMs promoted the osteogenic differentiation of stem cells. In vivo, the ability of bone regeneration was studied by way of implanting a BMSC/HM system in the cranial defect of rats for 8 weeks. The results confirmed that the BMSC/HM system can induce superior bone regeneration compared with both the HMs alone group and the untreated control group. This study provides a simple and effective research idea for bone defect repair, and the subsequent optimization study of HMs will provide a carrier material with application prospects for tissue engineering in the future.

Leveraging the Recent Advancements in GelMA Scaffolds for Bone Tissue Engineering: An Assessment of Challenges and Opportunities

“…76 Additionally, microfluidic technology has been employed to create GelMA hydrogel microspheres (HMs) for bone regeneration. 77 Teng et al fabricated GelMA HMs to treat calvarial defects in rats. The microspheres were found to have a size of 282.92 ± 3.82 μm and a stiffness of 2.28 kPa.…”

“…Injecting seeded microspheres into rat calvarial defects resulted in higher bone formation compared to the groups treated with microspheres without cells and the untreated group (Figure 5D). 77 The casting method is a cost-effective and straightforward approach for generating gels used in tissue engineering as it does not necessitate sophisticated equipment. Moreover, this method is not constrained by considerations such as shear thinning behavior or printability, which are significant in more intricate techniques.…”

Well-orchestrated physico-chemical and biological factors for enhanced secretion of osteogenic and angiogenic extracellular vesicles by mesenchymal stem cells in a 3D culture format

“…For example, MSCs cultured in the hydrogels of gelatin methacrylate (GelMA) stimulate osteogenic differentiation of MSCs. 54 Hence, tissue-derived materials like decellularized ECM, hyaluronic acid, chondroitin sulfate, collagen, fibronectin, and alginate are the preferred choices for tissue regeneration approaches. Natural scaffold materials possess more cell affinity and less cytotoxicity due to their degraded products and naturally carry cell attachment sites.…”

Effects of pre-osteogenic differentiation on the bone regeneration potentiality of marrow mesenchymal stem cells/poly(ethylene glycol)-diacrylate hydrogel using a rat cranial defect model

“…8 Other studies confirmed that the cell/hydrogel system could promote bone formation in calvarial defects and segmental bone defects. 9,10…”

“…8 Other studies confirmed that the cell/ hydrogel system could promote bone formation in calvarial defects and segmental bone defects. 9,10 Although a number of studies have detailed the cell delivery with hydrogels, 11,12 few studies have focused on the effect of pre-osteogenic differentiation on the in vivo osteogenesis for cell/hydrogel constructs, and the results are mixed. Corn et al prepared undifferentiated MSCs, which were encapsulated into alginate hydrogel and were implanted into bone defects immediately.…”