Design of a multiphase osteochondral scaffold. II. Fabrication of a mineralized collagen–glycosaminoglycan scaffold

Abstract

This paper is the second in a series of papers describing the design and development of an osteochondral scaffold using collagen-glycosaminoglycan and calcium phosphate technologies engineered for the regenerative repair of articular cartilage defects. The previous paper described a technology (concurrent mapping) for systematic variation and control of the chemical composition of triple coprecipitated collagen, glycosaminoglycan, and calcium phosphate (CGCaP) nanocomposites without using titrants. This paper describes (1) fabricating porous, three-dimensional scaffolds from the CGCaP suspensions, (2) characterizing the microstructure and mechanical properties of such scaffolds, and (3) modifying the calcium phosphate mineral phase. The methods build on the previously demonstrated ability to vary the composition of a CGCaP suspension (calcium phosphate mass fraction between 0 and 80 wt %) and enable the production of scaffolds whose pore architecture (mean pore size: 50-1000 microm), CaP phase chemistry (brushite, octacalcium phosphate, apatite) and crosslinking density (therefore mechanical properties and degradation rate) can be independently controlled. The scaffolds described in this paper combine the desirable biochemical properties and pore architecture of porous collagen-glycosaminoglycan scaffolds with the strength and direct bone-bonding properties of calcium phosphate biomaterials in a manner that can be tailored to meet the demands of a range of applications in orthopedics and regenerative medicine.

Composite Growth Factor Supplementation Strategies to Enhance Tenocyte Bioactivity in Aligned Collagen-GAG Scaffolds

“…[13][14][15][16][17] CG scaffolds have also been adapted for a variety of orthopedic applications covering osteochondral, bone, and tendon tissue engineering. [18][19][20][21] We have recently demonstrated a directional freeze-drying method to create geometrically anisotropic CG scaffolds with aligned tracks of ellipsoidal pores that mimic elements of native tendon anisotropy. 21 While we showed that the platelet-derived growth factor BB (PDGF-BB) and the insulin-like growth factor 1 (IGF-1) promoted increased tenocyte proliferation and migration within these anisotropic scaffolds, 21 a major concern remains the trade-off between increased proliferation and retention of the tenocyte-associated phenotype.…”

Biomimetic Scaffolds for Osteogenesis

“…Early timepoints of 4 and 7 days revealed increased osteogenic and angiogenic markers in mesenchymal stem cells seeded on a PLGA scaffold, while long-term mineralization endpoints at 8 weeks favored the collagen scaffolds. However, without an inorganic component, such collagen scaffolds have been found to lack structural strength and demonstrate significant contraction during mineralization [21][22][23] .…”

“…Combining the organic and inorganic components of the extracellular matrix using a novel nanoparticulate mineralized collagen glycosaminoglycan resulted in a highly osteogenic and structurally stable scaffold for both primary rabbit bone marrow stromal cells and primary human mesenchymal stem cells [23,[28][29][30] .…”

Collagen-Based Drug Delivery Systems for Tissue Engineering

“…7) or glycosaminoglycans (Harley & Gibson, 2008;Wang et al, 2010). Another combination of collagen scaffolds is represented by mineralization with calcium phosphate (Du et al, 2000;Harley et al, 2010) and/or on cross-linking with other substances like hydroxyapatite (Dubey & Tomar, 2009;Liao et al, 2009. ) or bushite (Tebb et al, 2006).…”