Recombinant Human Bone Morphogenic Protein-2 Immobilized Fabrication of Magnesium Functionalized Injectable Hydrogels for Controlled-Delivery and Osteogenic Differentiation of Rat Bone Marrow-Derived Mesenchymal Stem Cells in Femoral Head Necrosis Repair

Abstract

Femoral head necrosis (FHN) is a clinically progressive disease that leads to overwhelming complications without an effective therapeutic approach. In recent decades, transplantation of mesenchymal stem cells (MSCs) has played a promising role in the treatment of FHN in the initial stage; however, the success rate is still low because of unsuitable cell carriers and abridged osteogenic differentiation of the transplanted MSCs. Biopolymeric-derived hydrogels have been extensively applied as effective cell carriers and drug vesicles; they provide the most promising contributions in the fields of tissue engineering and regenerative medicine. However, the clinical potential of hydrogels may be limited because of inappropriate gelation, swelling, mechanical characteristics, toxicity in the cross-linking process, and self-healing ability. Naturally, gelated commercial hydrogels are not suitable for cell injection and infiltration because of their static network structure. In this study, we designed a novel thermogelling injectable hydrogel using natural silk fibroin-blended chitosan (CS) incorporated with magnesium (Mg) substitutes to improve physical cross-linking, stability, and cell osteogenic compatibility. The presented observations demonstrate that the developed injectable hydrogels can facilitate the controlled delivery of immobilized recombinant human bone morphogenic protein-2 (rhBMP-2) and rat bone marrow-derived MSCs (rBMSCs) with greater cell encapsulation efficiency, compatibility, and osteogenic differentiation. In addition, outcomes of in vivo animal studies established promising osteoinductive, bone mineral density, and bone formation rate after implantation of the injectable hydrogel scaffolds. Therefore, the developed hydrogels have great potential for clinical applications of FHN therapy.

Harnessing the Stem Cell Niche in Regenerative Medicine: Innovative Avenue to Combat Neurodegenerative Diseases

“…For example, neural stem cells displayed improved survival and differentiation when transplanted in hydrogel scaffolds containing laminin, an ECM protein found in neurogenic niches [93]. Controlled release of niche factors like BMP-2 from degradable microparticles embedded within cell scaffolds also promoted stem cell differentiation [94,95]. In addition to directly supporting transplanted cells, biomaterial scaffolds can be used to divert endogenous stem cells into injured areas.…”

Tissue‐engineered tracheal implants: Advancements, challenges, and clinical considerations

“…90 Notably, hydrogels have demonstrated their efficacy in promoting cellular infiltration and vascularization, showcasing successful applications in diverse areas such as skin wound healing, 91 bone regeneration, 92 and abdominal wall reconstruction. 93 Examples encompass patterned 2-hydroxyethyl methacrylate hydrogels, closely mimicking the mechanical properties of native airway, 94 and type I collagen, hydrogels like fibrin and agarose, which have demonstrated efficacy in supporting the growth of cultured respiratory ciliated epithelium and vascular venation. 95 While the use of hydrogels as artificial prosthetics is presently constrained, preliminary investigations in line with graft requirements have yielded promising results.…”

A Review of the Role of Tendon Stem Cells in Tendon-Bone Regeneration

“…In a study of bone tissue regeneration using porous nanofiber scaffolds, Wang et al studied BMP-2 local delivery from poly(lactic acid-glycolic acid) microspheres, and these composite scaffolds loaded with BMP-2 had high bone inductance, suggesting that the constructed BMP-2-loaded composite scaffold has the potential to be used as bone implants, and the extended release of BMP-2 promotes the osteogenic capacity of bone implants [ 75 ]. The observations of Lu et al [ 76 ] show that injectable hydrogels can be developed to deliver immobilized human bone morphogenetic protein-2 (rhBMP-2) and MSCs derived from rat bone marrow (rBMSC), with superior encapsulation efficiency, compatibility, and osteogenic differentiation. Moreover, in vivo studies show that injectable hydrogel scaffolds induce bone formation, bone density, and mineral density.…”