Department of Orthopedics, Third Xiangya Hospital of Central South University, Changsha, China.
Department of Bioengineering, University of Washington, Seattle, WA, USA.
Cell Transplant. 2024 Jan-Dec;33:9636897241276733. doi: 10.1177/09636897241276733.
Bone morphogenetic protein-2 (BMP-2) has been commercially approved by the Food and Drug Administration for use in bone defects and diseases. BMP-2 promotes osteogenic differentiation of mesenchymal stem cells. In bone tissue engineering, BMP-2 incorporated into scaffolds can be used for stimulating bone regeneration in organoid construction, drug testing platforms, and bone transplants. However, the high dosage and uncontrollable release rate of BMP-2 challenge its clinical application, mainly due to the short circulation half-life of BMP-2, microbial contamination in bone extracellular matrix hydrogel, and the delivery method. Moreover, in clinical translation, the requirement of high doses of BMP-2 for efficacy poses challenges in cost and safety. Based on these, novel strategies should ensure that BMP-2 is delivered precisely to the desired location within the body, regulating the timing of BMP-2 release to coincide with the bone healing process, as well as release BMP-2 in a controlled manner to optimize its therapeutic effect and minimize side effects. This review highlights improvements in bone tissue engineering applying spatiotemporal and controlled BMP-2 delivery, including molecular engineering, biomaterial modification, and synergistic therapy, aiming to provide references for future research and clinical trials.
骨形态发生蛋白-2（BMP-2）已获美国食品和药物管理局批准用于治疗骨缺损和疾病。BMP-2 可促进间充质干细胞的成骨分化。在骨组织工程中，与支架结合的 BMP-2 可用于刺激类器官构建、药物测试平台和骨移植中的骨再生。然而，BMP-2 的高剂量和不可控释放率对其临床应用构成挑战，主要原因是 BMP-2 的循环半衰期短、骨细胞外基质水凝胶中的微生物污染以及递送方式。此外，在临床转化中，BMP-2 为了达到疗效所需的高剂量给成本和安全带来了挑战。基于这些原因，新型策略应该确保 BMP-2 能够精确地递送到体内的预期位置，调节 BMP-2 释放的时间以与骨愈合过程相吻合，并以受控的方式释放 BMP-2，以优化其治疗效果并最小化副作用。本综述强调了应用时空和可控 BMP-2 递送来改善骨组织工程，包括分子工程、生物材料修饰和协同治疗，旨在为未来的研究和临床试验提供参考。
