BMP-2 in Orthopedic Trauma and Limb Reconstruction: Current Evidence, Limitations, and Future Directions

Background/Objectives: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is an osteoinductive agent increasingly used in many orthopedic cases such as fracture healing, nonunion, critical-sized bone defects, and limb reconstruction cases. However, its efficacy and safety remain controversial especially regarding its optimal dosing, delivery, and adverse effect concerns. This narrative review aims to summarize the rhBMP-2 evidence in orthopedic trauma and limb reconstruction. Methods: A literature search was conducted on PubMed/MEDLINE, Scopus, and Web of Science up to August 2026. We prioritized meta-analyses, systematic reviews, randomized controlled trials, and clinical studies. Results: rhBMP-2 induces osteogenic differentiation, endochondral ossification, and bone regeneration through canonical Smad-dependent and non-canonical pathways. Current evidence suggests a potential use of rhBMP-2 as an adjunct in selected open fractures, delayed union and nonunion, and complex reconstruction patients, although the results are still heterogeneous. Some studies reported fewer secondary interventions in open tibial fractures, while others failed to reproduce a consistent advantage over standard care or autograft. Hydroxyapatite-based delivery systems have recently demonstrated promising union rates at lower total rhBMP-2 doses, suggesting that the carrier and delivery method may determine the effect. Currently available studies carry clear weaknesses: small samples, few adequately powered trials, heterogeneous indications, no established optimal dose, high cost, and complications that include inflammation and ectopic bone formation. Controlled-release scaffolds, heparin-based microparticles, biomimetic carriers, and gene- or mRNA-based delivery are future research directions currently under investigation. Conclusions: rhBMP-2 is a promising adjunct that may benefit selected high-risk patients, but it does not replace stable fixation, infection control, soft-tissue management, or autologous grafting. Further trials are needed to define appropriate patient selection, the minimum effective dose, and optimal delivery systems.