Bio-Medical Research Institute, Kyungpook National University Hospital, Daegu, 41940, Republic of Korea.
Joint Institute for Regenerative Medicine, Kyungpook National University, Daegu, 41940, Republic of Korea.
Tissue Eng Regen Med. 2023 Dec;20(7):1205-1217. doi: 10.1007/s13770-023-00591-4. Epub 2023 Oct 10.
Current therapies to effectively treat long-bone defects and extensive bone tissue loss remains limited. In this study, we created a new bone substitute by integrating advanced technologies such as structure patterning, controlled release of a bone growth factor and conjugation system for clinically effective bone regeneration. This novel bioactive bone substitute was evaluated for its safety and efficacy using a rabbit ulna model.
A three dimensional bone patterned cylindrical structure with 1.5 cm in length and 5 mm in diameter was printed using poly(L-lactic acid)(PLLA) as a weight-bearing support and space-filling scaffold. And a bone morphogenetic protein 2 (BMP2) was employed to enhance bone regeneration, and coated to a 3D PLLA using alginate catechol and collagen to prolong the release kinetics. This novel bone substitute (BS)was evaluated for its physico-chemical and biological properties in vitro, and histological analysis and radiographical analysis such as X-ray, CT and micro-CT image analysis were performed to evaluate new bone formation in vivo.
The BS possesses an ideal shape and mechanically suitable proeperties for clinical use, with an easy-to-grab and break-resistant design at both ends, 80 ± 10 MPa of compression strength, and BMP2 release for two months. Histological analysis demonstrated the biocompability of BS with minimal inflammation and immune response, and X-ray, CT and micro-CT demonstrated effective new bone formation in rabbit ulna defect model.
The preclinical study of a novel bioactive bone substitute has shown its safe and effective properties in an animal model suggesting its clinical potential.
目前，有效治疗长骨缺损和广泛骨组织损失的治疗方法仍然有限。在这项研究中，我们通过整合先进技术，如结构图案化、骨生长因子的控制释放和偶联系统，创建了一种新的骨替代物，以实现临床有效的骨再生。本研究使用兔尺骨模型评估了这种新型生物活性骨替代物的安全性和有效性。
使用聚（L-乳酸）（PLLA）作为承重支撑和空间填充支架，打印出长度为 1.5cm、直径为 5mm 的三维骨图案化圆柱形结构。并使用骨形态发生蛋白 2（BMP2）来增强骨再生，并使用藻酸盐儿茶酚和胶原蛋白将其涂覆到 3D PLLA 上，以延长释放动力学。体外评估新型骨替代物（BS）的物理化学和生物学特性，进行组织学分析和 X 射线、CT 和微 CT 图像分析等影像学分析，以评估体内新骨形成。
BS 具有理想的形状和适合临床使用的机械性能，两端易于抓取且不易折断，压缩强度为 80±10MPa，BMP2 释放持续两个月。组织学分析表明 BS 具有良好的生物相容性，炎症和免疫反应极小，X 射线、CT 和微 CT 显示兔尺骨缺损模型中有效形成新骨。
新型生物活性骨替代物的临床前研究表明，其在动物模型中具有安全有效的特性，提示其具有临床应用潜力。
