In Situ Crosslinking Elastin-Like Polypeptide Gels for Application to Articular Cartilage Repair in a Goat Osteochondral Defect Model

Abstract

The objective of this study was to evaluate an injectable, in situ crosslinkable elastin-like polypeptide (ELP) gel for application to cartilage matrix repair in critically sized defects in goat knees. One cylindrical, osteochondral defect in each of seven animals was filled with an aqueous solution of ELP and a biocompatible, chemical crosslinker, while the contralateral defect remained unfilled and served as an internal control. Joints were sacrificed at 3 (n = 3) or 6 (n = 4) months for MRI, histological, and gross evaluation of features of biomaterial performance, including integration, cellular infiltration, surrounding matrix quality, and new matrix in the defect. At 3 months, ELP-filled defects scored significantly higher for integration by histological and gross grading compared to unfilled defects. ELP did not impede cell infiltration but appeared to be partly degraded. At 6 months, new matrix in unfilled defects outpaced that in ELP-filled defects and scored significantly better for MRI evidence of adverse changes, as well as integration and proteoglycan-containing matrix via gross and histological grading. The ELP-crosslinker solution was easily delivered and formed stable, well-integrated gels that supported cell infiltration and matrix synthesis; however, rapid degradation suggests that ELP formulation modifications should be optimized for longer-term benefits in cartilage repair applications.

In-Situ Forming Biomimetic Hydrogels for Tissue Regeneration

“…These hydrogels degraded rapidly. (Nettles et al, 2008) Table 3. In-situ forming hydrogels for in vivo cartilage regeneration…”

Neural Network Analysis Identifies Scaffold Properties Necessary for In Vitro Chondrogenesis in Elastin-like Polypeptide Biopolymer Scaffolds

“…A biocompatible, trifunctional, amine-reactive crosslinker, b-[tris(hydroxymethyl) phosphino] propionic acid (betaine) (THPP; Pierce Biotechnology, Rockford, IL), 20,48,57 was dissolved in 200 mL of 25 mM HEPES-buffered saline to a final concentration of 250 mg=mL. Aliquots of this solution were stored at À808C until further use.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14] Scaffolds have included those that are prefabricated ex situ 4,9,[15][16][17] or those that may be injected, [18][19][20] and they have been formed from a variety of natural and synthetic materials. Several studies have demonstrated that material formulation parameters affect the mechanical properties of these scaffolds as well as their ability to support chondrogenesis by encapsulated or seeded cells.…”

Sequential growth of long DNA strands with user-defined patterns for nanostructures and scaffolds

“…Structural proteins like elastin, collagen and silk often contain repeating peptide motifs, and are therefore translated from repeating DNA sequences 7 . This has sparked an interest in engineered 'proteinpolymers,' developed with similar motifs from repeating DNA to optimize structural properties 8,9 .…”