新型重组异种骨移植物的评价：使用处理过的牛松质骨与纯化牛骨形态发生蛋白相结合。

Evaluation of a novel reconstituted bone xenograft using processed bovine cancellous bone in combination with purified bovine bone morphogenetic protein.

机构信息

Institute of Orthopaedics and Traumatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

出版信息

Xenotransplantation. 2012 Mar-Apr;19(2):122-32. doi: 10.1111/j.1399-3089.2012.00694.x.

DOI:10.1111/j.1399-3089.2012.00694.x

PMID:22497514

Abstract

BACKGROUND

Xenogeneic grafting represents an alternative to autogenous grafting in osseous reconstruction and exhibits many beneficial properties. However, the usefulness of xenogeneic bone relies on necessary processing procedures for removing antigens and viruses, and preserving biological activities simultaneously. By chemical treatment of bovine cancellous bone to make it an antigen-free scaffold, and extraction of bone morphogenetic protein (BMP) from bovine cortical bone, followed by recombination of the scaffold with the BMP, we developed a new grafting material, reconstituted bone xenograft (RBX).

METHODS

In this study, scanning electron microscope and energy dispersive X-ray were first employed to observe the structure and components of RBX. Then the biomechanical property was evaluated by applying compression in a materials testing machine. Subsequently, the immunologic evaluation was performed by measuring galactose-alpha-1,3-galactose (α-gal) epitope in vivo and proinflammatory cytokine (TNF-α) secreted by human monocytic cell line (THP-1) in vitro. Finally, this RBX was implanted into segmental radial defects in a rabbit model, and its ability to treat large bone defects was specifically evaluated.

RESULTS

Although the compressive strength of RBX was 10% lower than that of unprocessed bovine cancellous bone (UBCB), the basic porous structure and natural components were still kept in this composite. The α-gal xenoantigen level was significantly lower in RBX (P < 0.05) compared with UBCB. Moreover, the TNF-α level was significantly (P < 0.05) reduced compared with UBCB when THP-1 was exposed to RBX. On the other hand, RBX appeared to induce cartilage formation from immature cell populations and resulted in osteogenesis through endochondral-like ossification from 4 to 12 weeks in repairing segmental bone defects.

CONCLUSIONS

These results demonstrate that RBX, with its natural microstructure and components, certain mechanical strength and strong osteoinductivity without evoking immune rejection, has significant potential for the treatment of bone defects.

摘要

背景

异种移植物在骨重建中是自体移植物的一种替代物，具有许多有益的特性。然而，异种骨的用途依赖于去除抗原和病毒的必要处理程序，同时保持生物活性。通过对牛松质骨进行化学处理使其成为无抗原支架，并从牛皮质骨中提取骨形态发生蛋白（BMP），然后将支架与 BMP 重组，我们开发了一种新的移植物材料，即重组异种骨（RBX）。

方法

本研究首先采用扫描电子显微镜和能谱仪观察 RBX 的结构和成分。然后，通过材料试验机进行压缩试验评估生物力学性能。随后，通过体内测量半乳糖-α-1,3-半乳糖（α-gal）表位和体外人单核细胞系（THP-1）分泌的促炎细胞因子（TNF-α）进行免疫评价。最后，将这种 RBX 植入兔桡骨节段缺损模型中，专门评估其治疗大骨缺损的能力。

结果

尽管 RBX 的抗压强度比未处理的牛松质骨（UBCB）低 10%，但这种复合材料仍保留了基本的多孔结构和天然成分。与 UBCB 相比，RBX 的 α-gal 异种抗原水平显著降低（P < 0.05）。此外，当 THP-1 暴露于 RBX 时，与 UBCB 相比，TNF-α 水平显著降低（P < 0.05）。另一方面，RBX 似乎能够从未成熟的细胞群诱导软骨形成，并通过软骨内成骨样骨化从 4 周到 12 周在修复节段性骨缺损中诱导成骨。