A hybrid tissue engineering construct enabling sustained BMP2 delivery outperforms a clinically used collagen sponge in large bone defect repair: A preclinical study
Year: 2026
Type: article
Abstract: 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.
Source: Biomedical Technology
Authors: Hirotsugu Maekawa, Seyedsina Moeinzadeh, Elaine Lui, Tomohiro Uno, Hossein Vahid Alizadeh, Jiannan Li, Andrea Sofia Flores Perez, Richard Sammy Muniz, Sungwoo Kim, Ashley M. Potter, Chloe Brekhus, Dan Regan, Drew W. Koch, Masanori Kobayashi, Toshiyuki Kawai, Shuichi Matsuda, Ben Gadomski, Jeremiah T. Easley, Jeffrey L. Young, Michael Gardner, David G. Mohler, William J. Maloney, Yunzhi P. Yang
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: diamond
OpenAlex ID: W7208745761