新型可注射水凝胶/胶原/纳米羟基磷灰石复合物在脊柱后柱不规则骨缺损修复修复中的应用基础研究

Bone related diseases are a kind of serious diseases in clinical field, which have significant effect on peoples' health and life quality. Repairing the bone defects with irregular shape is still a problem of orthopedics to be solved. In particular, recovering of defects in vertebral plate, spinous process and zygapophysis, is one needful follow-up treatment in spine surgery. In clinical practice, the defect sites are usually reconstructed by implanting autologous, allogenic bone or active biomaterials to recover tissue functions, thus alleviate patients' pain and improve their life qualities. However, implanting autologous or allogenic bone may face various risks such as increased wounds, limited donor, disease infection, immunological rejection,and etc.Therefore, in this project, we will use biodegradable and biocompatible thermo-sensitive hydrogel as a carrier to delivery bioactive bone growth factor, and then combine it with collagen fibers and calcium phosphate to prepare an injectalbe multi-component hydrogel composites to repaire the irregular bone defects. Such injectable hydrogel system will be used to repair the spinal defects in rabbits, and its capacity of guided bone regeneration in situ will be evaluated simultaneously. Our goal in this study is to establish a platform technology of fabricating a novel biodegradable thermo-sensitive PECE hydrogel which can be injected in vivo and cleared from the body under control, a technology of achieving controlled release of bioactive protein drugs through nanotechnology. We hope that our project could play a solid foundation to develop novel biomaterial for repairing irregular bone defects,and provide idea or perspective for choosing suitable biomaterials to reconstruct bone defects after spine surgery.

骨相关疾病是严重危害人类健康和生活质量的重大疾病，对不规则形状的骨缺损进行修复一直是临床一种比较常见的骨科疾病需要解决的问题之一。临床上主要是采用自体骨、异体骨或活性仿生生物材料在缺损部位进行修复重建，以部分或全面恢复缺损区域组织功能，减轻患者痛苦并提高生活质量，而采用自体或异体骨移植会面临增加创伤、供体有限、疾病传染或免疫排斥等风险。本项目拟采用一种生物相容性好、且体内降解速度可控的温度敏感水凝胶作为骨生长活性因子的载体，并与胶原纤维和活性磷酸钙盐复合得到可注射的多组分活性骨修复材料，用于动物脊柱后柱不规则骨缺损修复重建实验，并评价该复合体系在骨组织重建中的原位引导/诱导成骨作用。通过本项目实施我们将建立制备可体内外注射的温度敏感型水凝胶（PEG-PCL-PEG）的平台技术、通过纳米技术解决活性蛋白药物缓控释的平台技术和可注射纳米复合物的平台技术，为解决脊柱术后不规则缺损重建奠定基础。

骨骼是人体重要器官，担负着支撑、保护、造血、贮钙、代谢等功能，其本身就具有再生和自我修复的能力。随着人口老龄化、社会生活节奏加快及交通意外事故增多，与骨相关的疾病越来越成为严重影响人们健康和生活质量的疾病，例如骨质病变、骨肿瘤、骨折不愈合、陈旧性骨折、脊柱后柱去皮质化等疾病都会造成一些大面积的骨缺损. 可注射温度敏感性水凝胶作为良好的组织再生修复体系， 取代了自体骨、异体骨移植，解决了二次创伤、免疫排斥、疾病传染等问题。而且随着时间的累积, 水凝胶逐渐降解，也为骨的生长提供了空间。我们成功制备了胶原/羟基磷灰石/BMP-2水凝胶复合体系，并将纺丝膜包裹于外部增大生物利用度，对成骨效果起到了促进作用。此基础上我们还建立了ABM/PECE水凝胶复合体系、纳米羟基磷灰石 PLLA (HAp/PLLA)介孔微球复合体系等进行研究，均具有较明显的促进成骨效果。此外我们还构建了软组织修复体系，由于关节软骨缺乏修复能力，因此开发组织工程支架对关节病人尤为重要我们制备了包括硫酸软骨素/mPEG-PCL/氧化石墨烯（CSMA/PECA/GO ）复合支架和可注射PCEC多孔微球/海藻酸钠（MPs/Alg）水凝胶用于软骨修复，其具有较大的应用前景；包括多孔 PLA微球/胶原凝胶复合物用于软组织凹陷的修复，取得了较理想的效果。