Fabrication of intrafibrillar and extrafibrillar mineralized collagen/apatite scaffolds with a hierarchical structure

Abstract

A biomimetic collagen-apatite (Col-Ap) scaffold resembling the composition and structure of natural bone from the nanoscale to the macroscale has been successfully prepared for bone tissue engineering. We have developed a bottom-up approach to fabricate hierarchically biomimetic Col-Ap scaffolds with both intrafibrillar and extrafibrillar mineralization. To achieve intrafibrillar mineralization, polyacrylic acid (PAA) was used as a sequestrating analog of noncollagenous proteins (NCPs) to form a fluidic amorphous calcium phosphate (ACP) nanoprecursor through attraction of calcium and phosphate ions. Sodium tripolyphosphate was used as a templating analog to regulate orderly deposition of apatite within collagen fibrils. Both X-ray diffraction and Fourier transform infrared spectroscopy suggest that the mineral phase was apatite. Field emission scanning electron microscopy, transmission electron microscopy, and selected area electron diffraction confirmed that hierarchical collagen-Ap scaffolds were produced with both intrafibrillar and extrafibrillar mineralization. Biomimetic Col-Ap scaffolds with both intrafibrillar and extrafibrillar mineralization (IE-Col-Ap) were compared with Col-Ap scaffolds with extrafibrillar mineralization only (E-Col-Ap) as well as pure collagen scaffolds in vitro for cellular proliferation using MC3T3-E1 cells. Pure collagen scaffolds had the highest rate of proliferation, while there was no statistically significant difference between IE-Col-Ap and E-Col-Ap scaffolds. Thus, the bottom-up biomimetic fabrication approach has rendered a group of promising Col-Ap scaffolds, which bear high resemblance to natural bone in terms of composition and structure.

Osseointegration effect of biomimetic intrafibrillarly mineralized collagen applied simultaneously with titanium implant: A pilot in vivo study

“…The difference in new bone formation may be due to differences in the nanostructures of IMC and EMC. Unlike EMC, which is fabricated by a conventional crystallization method and lacks a surface chemistry and nanostructure similar to that of bone extracellular matrix (Hu et al, ; Liu et al, ), IMC is fabricated via a biomimetic strategy to achieve properties that mimic those of native bone (Feng et al, ; Lian et al, ; Liao et al, ; Qiu et al, ). IMC can promote nutrient transport, blood vessel ingrowth, and osteogenic cell migration throughout the scaffold (Liao et al, ; Liu et al, ).…”

“…Jawbone defect reconstruction that restores bone continuity and allows for dental rehabilitation remains a challenge for surgeons (Shen et al, 2017;Shnayder et al, 2015;Zhang et al, 2015). The achieve- (Hu et al, 2016;Liu et al, 2014), IMC is fabricated via a biomimetic strategy to achieve properties that mimic those of native bone (Feng et al, 2016;Lian et al, 2013;Liao et al, 2004;Qiu et al, 2015). IMC can promote nutrient transport, blood vessel ingrowth, and osteogenic cell migration throughout the scaffold (Liao et al, 2004;Liu et al, 2016).…”

Biomimetic intrafibrillar mineralized collagen promotes bone regeneration via activation of the Wnt signaling pathway

“…5,7,11 The EMC scaffold materials were fabricated by a conventional crystallization method. 6 Samples were prepared with a pore size of 100-400 µm and a porosity of 85%-95%. The scaffolds used for the in vivo study were in the shape of a cylinder that was 5 mm in height and 4 mm in diameter; while for the in vitro study, they were in the shape of discs that were 1 mm in thickness and 12 mm in diameter.…”

“…However, previous studies have mainly focused on extrafibrillar mineralized collagen (EMC) fabricated by conventional crystallization methods, in which apatite crystallites are deposited randomly around the collagen fibrils. As natural bone needs to fit the variable mechanical demands via its hierarchically staggered nanostructure, the EMC can only produce similar chemical properties rather than the surface chemistry and nanostructure of bone extracellular matrix (ECM); 6 therefore, the strength of EMC is insufficient.…”

Biomimetic intrafibrillar silicification of collagen fibrils through a one-step collagen self-assembly/silicification approach

“…In our previous work, intrabrillar calcied collagen brils have been achieved by a one-step collagen self-assembly and calcication approach. 20,21 In the present study, we also propose to produce intrabrillar silicied collagen brils via a one-step collagen self-assembly/ silicication (OCSS) approach, where collagen self-assembly and silicication occur simultaneously with the aid of positive and negative analogs of zwitterionic proteins. To test this hypothesis, a systemic study was conducted to investigate the effect of zwitterionic proteins analogs on the OCSS approach, and an in vitro cell culture study was also conducted to test the biocompatibility of the intrabrillar silicied collagen brils.…”