Thompson Laboratory for Regenerative Orthopaedics, University of Missouri, Columbia, MO.
Department of Orthopaedic Surgery, University of Missouri, Columbia, MO.
J Orthop Trauma. 2024 Nov 1;38(11S):S40-S47. doi: 10.1097/BOT.0000000000002881.
Osteochondral allograft transplantation (OCAT) can be a successful joint restoration treatment option for large post-traumatic articular defects but is still associated with significant revision and failure rates. Despite recent advances that have improved OCAT success, insufficient osteochondral allograft (OCA) osseointegration remains a major cause of failure. Deferoxamine (DFO) is an effective angiogenic and osteo-anabolic iron chelator that consistently promotes bone neovascularization and regeneration. This study was designed to investigate local delivery of DFO for augmenting OCA osseointegration using a preclinical canine model for OCAT in the knee and hip as commonly affected joints.
On Institutional Animal Care and Use Committee (IACUC) approval, 12 purpose-bred dogs underwent OCAT of the femoral head or femoral condyles with DFO or DFO-free (controls) microspheres in recipient sites. OCA revascularization, cellular repopulation, and integration were evaluated based on functional, diagnostic imaging, microcomputed tomography, histology, and immunohistochemistry outcome measures.
Local delivery of DFO into OCAT recipient sites was associated with maintained or improved joint function, superior radiographic appearance, significantly greater trabecular thickness, higher bone volume, and new bone ingrowth compared with DFO-free controls.
OCA osseointegration is dependent on cellular repopulation and neovascularization, resulting in new bone ingrowth through creeping substitution, and insufficient osseointegration with resorption and subsidence of the OCA remains a major cause of failure after transplantation. The results of this study suggest that local delivery of DFO using a controlled microsphere release system may reduce resorption and improve revascularization and cellular repopulation to increase new bone ingrowth, potentially expediting OCA osseointegration after transplantation.
骨软骨同种异体移植（OCAT）可以作为治疗大创伤性关节缺损的成功关节重建治疗选择，但仍存在较高的翻修和失败率。尽管最近的进展提高了 OCAT 的成功率，但异体骨软骨（OCA）的骨整合不足仍然是主要的失败原因。去铁胺（DFO）是一种有效的血管生成和成骨合成铁螯合剂，可持续促进骨血管新生和再生。本研究旨在通过膝髋部 OCAT 的临床前犬模型，研究局部递送去铁胺（DFO）以增强 OCA 骨整合的效果，膝髋部是 OCAT 常见的受累关节。
在机构动物护理和使用委员会（IACUC）批准下，12 只特定繁殖的犬接受了股骨头或股骨髁的 OCAT，在供体部位使用 DFO 或不含 DFO（对照）微球。根据功能、诊断影像学、微计算机断层扫描、组织学和免疫组织化学结果评估 OCA 的再血管化、细胞再定植和整合。
局部递送去铁胺（DFO）到 OCAT 供体部位与维持或改善关节功能、更好的影像学表现、显著增加的小梁厚度、更高的骨体积和新骨长入有关，与不含 DFO（DFO）的对照组相比。
OCA 的骨整合取决于细胞再定植和血管新生，通过爬行替代导致新骨长入，而 OCA 的骨整合不足和吸收以及沉降仍然是移植后失败的主要原因。本研究结果表明，使用受控微球释放系统局部递送去铁胺（DFO）可能减少吸收并改善再血管化和细胞再定植，以增加新骨长入，从而在移植后加速 OCA 的骨整合。
