A bioactive intramedullary implant enables accelerated bone regeneration and early load-bearing in distraction...

Distraction osteogenesis (DO) remains limited by prolonged consolidation and delayed bone union. This study evaluated whether a biodegradable, bone morphogenetic protein-2 (BMP-2)-releasing intramedullary implant (IMI) could enhance bone regenerate formation in a rat monofocal femoral lengthening model. We developed a Hybrid Tissue Engineering Construct (HyTEC) comprising a 3D-printed polycaprolactone-β-tricalcium phosphate IMI coated with a BMP-2-loaded hydrogel. Rats underwent standardized lengthening in three groups: control (DO only), IMI (implant without BMP-2), and IMI-BMP2 (BMP-2-releasing implant), with evaluation at postoperative days 31 and 52. The IMI-BMP2 group demonstrated significantly superior osteogenesis, achieving a bone volume fraction of 80 ± 22% at day 31, compared to 35 ± 19% (IMI) and 54 ± 25% (control), indicating accelerated regenerate formation. Radiographic and histological analyses confirmed early, uniform callus formation, while immunohistochemistry revealed elevated osteocalcin expression. Mechanical testing demonstrated restoration of approximately 50% of normal bone strength by day 52. Transcriptomic profiling revealed an exploratory BMP-2-associated regenerative gene signature, suggesting coordinated early-phase regulation of remodeling and metabolic reprogramming. This bioactive implant accelerated bone union, facilitated improved early ambulation consistent with partial mechanical competence restoration, and significantly shortened consolidation time, representing a promising clinically translatable strategy to overcome conventional DO limitations and improve patient outcomes. STATEMENT OF SIGNIFICANCE: Distraction osteogenesis is an effective strategy for managing large bone defects, but its clinical use is limited by prolonged consolidation and delayed functional recovery. This study presents a biodegradable intramedullary implant that provides sustained bone morphogenetic protein-2 (BMP-2) delivery and markedly accelerates regenerate formation, improves early mechanical strength, and enables earlier weight-bearing in a rat femoral lengthening model. In addition to demonstrating therapeutic efficacy, the work identifies a BMP-2-associated regenerative transcriptional signature linked to remodeling, osteoclast activity, and metabolic reprogramming. These findings establish a clinically translatable biomaterial-based approach to shorten treatment time and improve outcomes in distraction osteogenesis.