An Injectable Multifunctional Dual‐Phase Bead‐Reinforced Gelatin Matrix Permissive of Mesenchymal Stem Cell Infiltration for Musculoskeletal Soft Tissue Repair

This study develops a novel strategy for regenerative therapy of musculoskeletal soft tissue defects using a dual‐phase multifunctional injectable gelatin‐hydroxyphenyl propionic acid (Gtn‐HPA) composite. The dual‐phase gel consists of stiff, degradation‐resistant, ≈2‐mm diameter spherical beads made from 8 wt% Gtn‐HPA in a 2 wt% Gtn‐HPA matrix. The results of a 3D migration assay show that both the cell number and migration distance in the dual‐phase gel system are comparable with the 2 wt% mono‐phase Gtn‐HPA, but notably significantly higher than for 8 wt% mono‐phase Gtn‐HPA (into which few cells migrated). The results also show that the dual phase gel system has degradation resistance and a prolonged growth factor release profile comparable with 8 wt% mono‐phase Gtn‐HPA. In addition, the compressive modulus of the 2 wt% dual‐phase gel system incorporating the 8 wt% bead phase is nearly four‐fold higher than the 2 wt% mono‐phase gel (5.3 ± 0.4 kPa versus 1.5 ± 0.06 kPa). This novel injectable dual‐phase Gtn‐HPA composite thus combines the advantages of low‐concentration Gtn‐HPA (cell migration) with high‐concentration Gtn‐HPA (stiffness, degradation resistance, slower chemical release kinetics) to facilitate effective reparative/regenerative processes in musculoskeletal soft tissue. A novel dual‐phase injectable gelatin‐hydroxyphenyl propionic acid (Gtn‐HPA) composite gel is developed consisting of high density Gtn‐HPA beads that provide mechanical strength, a degradation‐resistant compartment for prolonged in vivo function, and slow release of reparative factors (e.g., growth factors), and a low density Gtn‐HPA matrix for injectability and increased capacity for cell migration.