title: Biomimetically Ornamented Rapid Prototyping Fabrication of an Apatite-Collagen-Polycaprolactone Composite Construct with Nano-Micro-Macro Hierarchical Structure for Large Bone Defect Treatment.
abstract: 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 (∼100 nm thickness and ∼1 μm length) platelike apatite coating on the microporous (126 ± 18 μm) collagen networks, which homogeneously filled the macroporous (∼1000 μm) 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.
authors.forename: Jinbing
authors.initials: J
authors.lastname: Wang
authors.affiliation: National Tissue Engineering Center of China , 68 Jiang Chuan East Road, Shanghai 200241, PR China.
authors.forename: Dingyu
authors.initials: D
authors.lastname: Wu
authors.affiliation: National Tissue Engineering Center of China , 68 Jiang Chuan East Road, Shanghai 200241, PR China.
authors.forename: Zhanzhao
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Shen
authors.affiliation: National Tissue Engineering Center of China , 68 Jiang Chuan East Road, Shanghai 200241, PR China.
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Wang
authors.affiliation: National Tissue Engineering Center of China , 68 Jiang Chuan East Road, Shanghai 200241, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: National Tissue Engineering Center of China , 68 Jiang Chuan East Road, Shanghai 200241, PR China.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
mesh_terms: D000818:Animals; D001031:Apatites / Q000494:pharmacology*; D040761:Biomimetic Materials / Q000494:pharmacology*; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology*; D057927:Hydrophobic and Hydrophilic Interactions; D053758:Nanoparticles / Q000737:chemistry*; D016348:Osseointegration / Q000187:drug effects; D011091:Polyesters / Q000494:pharmacology*; D016062:Porosity; D011817:Rabbits; D013052:Spectrometry, X-Ray Emission; D017550:Spectroscopy, Fourier Transform Infrared; D013818:Thermogravimetry; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction; D055114:X-Ray Microtomography
chemical_list: D001031:Apatites; D011091:Polyesters; D014867:Water; C016240:polycaprolactone; D003094:Collagen
keywords: biomimetically functionalization; bone defect treatment; bone graft substitute; bone regeneration; hierarchical structure; osteoconduction; osteointegration; rapid prototyping technology