Incorporating Hydrogel (with Low Polymeric Content) into 3D‐Printed PLGA Scaffolds for Local and Sustained Release of BMP2 in Repairing Large Segmental Bone Defects

Abstract Treating large bone defects remains a considerable challenge for clinicians: bone repair requires scaffolds with mechanical properties and bioactivities. Herein, based on crosslinking o‐phthalaldehyde (OPA) with amine groups, 4‐arm polyethylene glycol (4armPEG)‐OPA/Gelatin hydrogel loaded with bone morphogenetic protein 2 (BMP2) is prepared and a three dimensional (3D)‐printed poly (lactic‐co‐glycolic acid) (PLGA) porous scaffold is filled with the hydrogel solution. The composite scaffold, with a compression modulus of 0.68 ± 0.097 GPa similar to the cancellous bone, has a porosity of 56.67 ± 4.72% and a pore size of about 380 µm, promoting bone growth. The hydrogel forms a porous network at low concentrations, aiding protein release and cell migration. The hydrogel degrades in approximately three weeks, and the scaffold takes five months, matching bone repair timelines. BMP2 release experiment shows a sustained BMP2 release with a 72.4 ± 0.53% release ratio. The ALP activity test and alizarin red staining shows effective osteogenic promotion, while RT‐PCR confirms BMP2@Gel enhanced COL‐1 and OPN expression. Animal experiments further validate the composite scaffold's bone repair efficacy. This study demonstrates the effectiveness of the hydrogel in releasing BMP2 and the mechanical support of the 3D‐printed PLGA porous scaffold, providing a new treatment for bone defects.