Stem cell-delivery hydrogels with shear-thinning injectability promote bone healing in distraction osteogenesis

Distraction osteogenesis (DO) is a widely used surgical procedure for limb lengthening, deformity correction, and management of segmental bone defects. However, delayed bone consolidation can lead to a long treatment time and poor healing quality, which remains an unsolved clinical problem. Herein, a bioactive injectable material (BIM) was developed to improve the clinical outcome of DO. A naturally-derived polymer (gelatin) composed of bioactive silicate-nanodisk (LAPONITE®) was crosslinked with natural-origin genipin. The BIM features sustainable linear release of pro-osteogenic components (Mg²⁺, Li⁺ and Si⁴⁺ ions) and linear biodegradability upon gradual tensile loading during the DO procedure. The BIM promoted the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro, with RUNX2 and OCN mRNA expression upregulated by 112% and 160%, respectively, and VEGF expression increased by 357% (p < 0.01). In a rat DO model, single injection of the MSC-laden BIM during the distraction phase significantly augmented healing quality, with BV/TV increasing by 358% and BMD by 288% compared to the control group (p < 0.01). Mechanical testing revealed a 243% increase in maximum load (p < 0.01), and immunohistochemical staining confirmed enhanced blood vessel formation. The special design of this novel injectable material together with MSC transplantation provides a novel strategy to reconstruct a favorable microenvironment for bone regeneration, unachievable by the traditional methods (using growth factors like BMP-2 or VEGF with high cost and poor stability), which provides insight into the development of a promising translatable biomaterial-enhanced strategy for DO.