ROLE OF STEM CELL THERAPY IN ENHANCING BONE REGENERATION IN SEVERE FRACTURE CASES

Abstract

Critical-sized bone fractures or those fractured in a compromised physiological condition commonly lead to delayed or non-unions because of insufficient natural healing ability. In this research, the researchers examined the effects of mesenchymal stem cell therapy in bone regeneration on a rat femoral critical-sized defect model, with four groups of treatments: control (no treatment), autograft (bone graft), MSC-collagen (MSCs on collagen scaffold), and MSC-hydrogel (MSCs in fibrin hydrogel). Micro-computed tomography, biomechanical testing, histological scoring, cytokine profiling, analysis of MSC polarization of macrophages, and computational modeling of MSC homing and osteogenic differentiation kinetics were identified as outcome measures. These findings showed that MSC-Hydrogel had better bone regeneration in all the parameters with bone volume fraction. The biomechanical result showed that MSC-Hydrogel had a maximum load to failure of 238.5 +/- 18.9 N compared to the control 48.3 +/- 8.2 N, or 393% higher. Immunomodulatory results indicated that MSC-Hydrogel minimized pro-inflammatory cytokines and changed the M1:M2 macrophage ratio from 4.38 in the control to 0.11, showing that MSC-Hydrogel polarized towards a pro-healing phenotype. Computational models showed better chemotactic sensitivity and homing efficiency (η = 0.81) of MSC-Hydrogel and a high correlation to bone volume fraction (R² = 0.96). The upregulation of Runx2 and Osterix was 9.6-fold and 10.3-fold in the MSC-Hydrogel group, respectively. The results indicate that hydrogel-transferred MSC therapy is a promising alternative to autografts to treat severe fracture non-unions due to its ability to activate a coordinated response of enhanced homing, immunomodulation, osteogenic differentiation, and neovascularization.