A hybrid tissue engineering construct enabling sustained BMP2 delivery outperforms a clinically used collagen sponge in large bone defect repair: A preclinical study

Background Large bone defects remain a major challenge in orthopedic surgery. Current treatments, including autologous bone grafting, collagen sponge-based BMP2 delivery, and distraction osteogenesis, are limited by donor-site morbidity, burst BMP2 release causing adverse effects, and surgical invasiveness. Engineered biomaterial platforms combining structural support with sustained growth-factor delivery offer a promising alternative, but few systems integrate structurally defined scaffold design, stable hydrogel incorporation, and compatibility with terminal sterilization workflows. Technology Here, we evaluated HyTEC, a hybrid tissue engineering platform that integrates a polycaprolactone–β-tricalcium phosphate scaffold with a GelMA/PEGDMA/alginate hydrogel network for sustained BMP2 delivery. A multistep surface-modification strategy combining covalent GelMA conjugation and surface-initiated alginate crosslinking was used to stabilize the scaffold–hydrogel interface. This integrated architecture combines structural support, controlled BMP2 delivery, compatibility with freeze-drying and terminal E-beam sterilization, and can be configured as a solid rod implant or a macroscopic 3D-printed porous scaffold. HyTEC was compared with an equal-dose BMP2-loaded collagen sponge control in a rat critical-sized femoral defect model, and scale-up feasibility was assessed in an exploratory sheep 5-cm metatarsal defect model. Results In vitro, rod-format HyTEC released 26.5% of BMP2 within 1 day and 79.9% by day 28, whereas the collagen sponge released 67.4% within 24 h. In the 3D-printed porous scaffold format, cumulative BMP2 release reached 17.2 ± 8.1% by day 7 and 62.7 ± 4.0% by day 70 and was monitored over 91 days. hMSC viability in HyTEC remained 92–96% over 7 days, confirming cytocompatibility of the scaffold–hydrogel construct. In the rat model, BMP2-loaded HyTEC achieved 100% bone union by POD 34 and significantly greater BV/TV at POD 55 than the equal-dose collagen sponge control (4.1-fold, P < 0.0001), together with greater mechanical recovery. In the pilot sheep study, the BMP2-loaded HyTEC scaffold specimen had a bone volume of 5126 mm 3 , compared with 2466 mm 3 for autograft and 1942 mm 3 for the collagen sponge, without obvious adverse tissue reactions; these observations do not permit statistical inference. These findings support HyTEC as a tissue engineering platform for sustained BMP2 delivery that is geometrically adaptable across implant scales. Powered large-animal studies, dose optimization, mechanistic evaluation, and safety assessment are needed to support clinical translation.