基于三维打印技术的体内生物反应器仿生构建组织工程骨

The repair of orbital bone defects caused by trauma, tumor or congenital anomaly, remains an immense challenge in reconstructive surgery. There are several types of artificial materials that are frequently used clinically for the orbital defect reconstruction. However, these materials are usually nondegradable or hard to be degraded, so they may cause rejection, infection, cyst formation, or implant metastasis. The clinical goal is to reconstruct custom-made three-dimensional bony tissue with blood vessel net in an anatomically functional morphology, which is an ideal approach for the treatment of orbital bone defects. Based on computer-aided design/computer-aided manufacturing (CAD/CAM), 3D printed technology and tissue engineer technology, the osteoinductive potential of the periosteum are stimulated using a type of biodegradable customized biomimetic scaffold and cells in vivo bioreactor. The osteoinductive potential of biomimetic scaffold and bone formation is evaluated. After the prefabrication of the custom-made bone grafts, the grafts are transplanted into defects of the orbital bone, performing a microsurgical anastomosis and using miniplates for fixation. The reconstructive orbital bones are evaluated regarding visual functional and esthetic outcome. This research work will develop a new protocol for bone prefabrication and the orbital defect reconstruction based on 3D printed technology, which has the potential to become an alternative for natural autogenous vascularized bone grafts and microsurgical transplantation for the orbital defect reconstruction in the clinic.

对外伤、肿瘤和先天异常等所导致的眼眶缺损进行修复重建是整形外科和眼科工作的难点。目前临床常用的眼眶修复材料存在排异反应、易感染和植入物移位等诸多问题。利用含有血管网络的定制型骨组织，解剖修复自体眶骨缺损是一种理想的解决方法。本研究将在前期工作的基础上，把三维打印技术和组织工程技术有机结合起来，三维打印定制型仿生可降解支架，在体内生物反应器预构含有血管网络的组织工程眶骨，修复兔自体眶骨缺损模型。检测体内生物反应器中，三维仿生支架的成骨潜能、优越性和机制，定制构建血管化骨组织的可行性和效果。应用定制的血管化骨组织修复自体眶骨缺损，从视功能和形态学角度对修复效果进行评估。阐明应用三维可降解仿生支架在体构建骨组织，并用来修复眶骨缺损的可行性及优越性。本研究为利用三维打印技术和生物体自身潜能构建骨组织，修复眶骨缺损提供了新思路，为进一步临床应用提供了理论依据。

对于复杂形状的大骨缺损的修复仍然是一个重要的临床挑战。本项目探讨了聚乳酸-羟基磷灰石（PLA-HA）复合支架的可行性。利用体内生物反应器（IVB）技术和三维打印技术构建血管化组织工程骨支架。我们建立了两组兔血管化组织工程骨模型。实验组（EG）采用三维打印（3DP）PLA-HA支架复合植入骨髓基质细胞（BMSCs）并用胫骨骨膜包裹。将3DP PLA/HA支架与自体骨髓间充质干细胞联合移植但无血管胫骨骨膜包裹作为对照组。4周和8周后，通过研究相关基因、显微CT（micro-CT）和组织学检查，分析新生血管和骨组织形成。结果表明，我们的方法能够在体内生成血管化组织工程骨。此外，我们观察到两组新生血管和新活骨形成的显著差异。在本研究中，我们证明了3DP PLA/HA复合支架在体内产生大血管化骨组织的可行性。