The development of collagen-GAG scaffold-membrane composites for tendon tissue engineering

Abstract

Current tissue engineering approaches for tendon defects require improved biomaterials to balance microstructural and mechanical design criteria. Collagen-glycosaminoglycan (CG) scaffolds have shown considerable success as in vivo regenerative templates and in vitro constructs to study cell behavior. While these scaffolds possess many advantageous qualities, their mechanical properties are typically orders of magnitude lower than orthopedic tissues such as tendon. Taking inspiration from mechanically efficient core–shell composites in nature such as plant stems and porcupine quills, we have created core–shell CG composites that display high bioactivity and improved mechanical integrity. These composites feature integration of a low density, anisotropic CG scaffold core with a high density, CG membrane shell. CG membranes were fabricated via an evaporative process that allowed separate tuning of membrane thickness and elastic moduli and were found to be isotropic in-plane. The membranes were then integrated with an anisotropic CG scaffold core via freeze-drying and subsequent crosslinking. Increasing the relative thickness of the CG membrane shell was shown to increase composite tensile elastic modulus by as much as a factor of 36 in a manner consistent with predictions from layered composites theory. CG scaffold-membrane composites were found to support tendon cell viability, proliferation, and metabolic activity in vitro, suggesting they maintain sufficient permeability while demonstrating improved mechanical strength. This work suggests an effective, biomimetic approach for balancing strength and bioactivity requirements of porous scaffolds for tissue engineering.

Incorporation of the natural marine multi-mineral dietary supplement Aquamin enhances osteogenesis and improves the mechanical properties of a collagen-based bone graft substitute

“…23 The least porous scaffold (500F) still achieved porosities in excess of 95%, significantly above the minimum level suggested to facilitate cell infiltration and for bone repair (~90%). 24 The porosity of the collagen GAG scaffold (99.4%) is in agreement with that reported in other studies (~99.5%). 25 Equally important, the permeability of the CollAqua scaffolds was such that it did not impede fluid flow through the scaffold demonstrating the high degree of interconnectivity of the pores within the scaffold.…”

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

“…20 Scaffolds were pulled to failure at a rate of 1 mm min -1 using an MTS Insight electromechanical load frame. The elastic modulus was calculated from the slope of the stress-strain curve over a strain range of 5%-10%.…”

“…The elastic modulus was calculated from the slope of the stress-strain curve over a strain range of 5%-10%. 20,53 Ultimate tensile strength was determined from the peak stress value on the stress-strain curve.…”

“…[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.…”

Decellularized Extracellular Matrix Derived from Porcine Adipose Tissue as a Xenogeneic Biomaterial for Tissue Engineering

“…A specimen (20 mm · 5 mm · 1 mm, length · width · thickness) was pulled at a rate of 2.54 mm/ min. 26,27 Strains were calculated using cross-head displacement, and stresses were calculated by dividing force data by the cross-sectional area of the sample. Three specimens were measured and averaged.…”