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.

Innovative biodegradable poly(L-lactide)/collagen/<br />hydroxyapatite composite fibrous scaffolds promote osteoblastic proliferation and differentiation

“…Therefore, scaffold-based polymer such as polycaprolactone (PCL) or polylactic acid (PLLA) were investigated for bone tissue engineering in recent years. [13][14][15] In vitro studies showed that a membrane system-based PCL can promote proliferation and early cell differentiation of osteoblast-like cells. 15 However, the disadvantage of the synthetic polymers is that it has a poor biocompatibility.…”

Recent advances in nano scaffolds for bone repair

“…The nanofibers provided typical ECM to cells, where these cells formed endothelial monolayer with higher confluency. 67 In Figure 1b, Wang et al 68 developed apatite-collagen-polycaprolactone (Ap-Col-PCL) composites that showed excellent bioactivity to promote fast bone regeneration in rabbit model with fractional long bone defect. They combined rapid prototyping (RP) fabrication technology and 3D functionalization strategy for biomimetic deposition and collagen incorporation.…”

“…These composite materials showed outstanding mechanical properties similar to cancellous bone, good biodegradability, and hierarchical architecture of three nano–micro–macro levels. 68 …”

The preosteoblast response of electrospinning PLGA/PCL nanofibers: effects of biomimetic architecture and collagen I

“…17 3) Fabricating functionally graded and multilayered membranes. 18 4) Incorporating osteoconductive calcium phosphate ceramics (eg, β-tricalcium phosphate, hydroxyapatite), 19,20 antibacterial agents (eg, metronidazole), bioactive proteins (eg, BMP-2), or growth factors (eg, stromal cell-derived factor-1α) into biodegradable polymers. 8,21 5) Modifying the biomembrane surface to graft bioactive molecules or proteins (eg, 3,4-dihydroxyphenylalanine [pDA]).…”

“…Therefore, COL I-pDA-PLGA/PCL ES membranes with interconnected pore networks may exhibit better mechanical function and better biological performance. 20 …”