Biomimetically Ornamented Rapid Prototyping Fabrication of an Apatite-Collagen-Polycaprolactone Composite Construct with Nano-Micro-Macro Hierarchical Structure for Large Bone Defect Treatment
Biomimetically Ornamented Rapid Prototyping Fabrication of an Apatite-Collagen-Polycaprolactone Composite Construct with Nano-Micro-Macro Hierarchical Structure for Large Bone Defect Treatment
复制标题
仿生装饰快速原型制造具有纳米-微米-宏观层次结构的磷灰石-胶原-聚己内酯复合结构，用于治疗大骨缺损
DOI：
10.1021/acsami.5b08534
复制
发表时间：
2015-12-02
影响因子：
9.5
通讯作者：
Sun, Jian
中科院分区：
文献类型：
--
作者：
Wang, Jinbing;Wu, Dingyu;Sun, Jian
基于生物材料的骨移植替代物具有良好的力学和生物学性能，可作为自体骨移植治疗大面积骨缺损的替代品。在这里，磷灰石胶原蛋白聚己内酯（Ap-Col-PCL）复合材料结构的开发与独特的纳米微观宏观层次结构相结合的快速成型（RP）制造技术和3D功能化策略。采用RP技术制备大孔PCL支架，并通过胶原蛋白掺入和仿生沉积进行功能化。Ap-Col-PCL复合材料构建体的特征在于具有纳米级的分级结构。（类似于100 nm的厚度和类似于1 μ m的长度）板状磷灰石涂层上的微孔（126 +/-18 μ m）胶原网络，它均匀地填充了大孔（类似于4000 μ m）PCL框架，并具有良好的亲水性和压缩模量（68.75 +/- 3.39 MPa）类似于松质骨。体外细胞培养实验和体内关键骨缺损植入实验表明，Ap-Col-PCL结构不仅能显著提高细胞粘附能力，（2.0倍），促进更快的细胞增殖，但也在12周内成功桥接节段性长骨缺损，并有更多的骨再生（5.2倍），更好的骨整合（7.2倍）和更快的新骨沉积速率（2.9倍）。我们的研究表明，生物仿生Ap-Col-PCL结构具有良好的力学性能，更多的骨组织长入，以及更好的骨整合能力，作为临界尺寸骨缺损治疗的有效骨移植替代物;同时，它还可以利用RP技术的优势，特别是便于在临床应用中根据医学图像定制植入物的形状和尺寸。
Biomaterial-based bone graft substitute with favorable mechanical and biological properties could be used as an alternative to autograft for large defect treatment. Here, an apatite collagen polycaprolactone (Ap-Col-PCL) composite construct was developed with unique nano micro macro hierarchical architectures by combining rapid prototyping (RP) fabrication technology and a 3D functionalization strategy. Macroporous PCL framework was fabricated using RP technology, then functionalized by collagen incorporation and biomimetic deposition. Ap-Col-PCL composite construct was characterized with hierarchical architectures of a nanoscale (similar to 100 nm thickness and similar to 1 mu m length) platelike apatite coating on the microporous (126 +/- 18 mu m) collagen networks, which homogeneously filled the macroporous (similar to 4000 mu m) PCL frameworks and possessed a favorable hydrophilic property and compressive modulus (68.75 +/- 3.39 MPa) similar to that of cancellous bone. Moreover, in vitro cell culture assay and in vivo critical-sized bone defect implantation demonstrated that the Ap-Col-PCL construct could not only significantly increase the cell adhesion capability (2.0-fold) and promote faster cell proliferation but also successfully bridge the segmental long bone defect within 12 weeks with much more bone regeneration (5.2-fold), better osteointegration (7.2-fold), and a faster new bone deposition rate (2.9-fold). Our study demonstrated that biomimetically ornamented Ap-Col-PCL constructs exhibit a favorable mechanical property, more bone tissue ingrowth, and better osteointegration capability as an effective bone graft substitute for critical-sized bone defect treatment; meanwhile, it can also harness the advantages of RP technology, in particular, facilitating the customization of the shape and size of implants according to medical images during clinical application.