Thermoreversible hydrogel scaffolds for articular cartilage engineering

Abstract

Articular cartilage has limited potential for repair. Current clinical treatments for articular cartilage damage often result in fibrocartilage and are associated with joint pain and stiffness. To address these concerns, researchers have turned to the engineering of cartilage grafts. Tissue engineering, an emerging field for the functional restoration of articular cartilage and other tissues, is based on the utilization of morphogens, scaffolds, and responding progenitor/stem cells. Because articular cartilage is a water-laden tissue and contains within its matrix hydrophilic proteoglycans, an engineered cartilage graft may be based on synthetic hydrogels to mimic these properties. To this end, we have developed a polymer system based on the hydrophilic copolymer poly(propylene fumarate-co-ethylene glycol) [P(PF-co-EG)]. Solutions of this polymer are liquid below 25°C and gel above 35°C, allowing an aqueous solution containing cells at room temperature to form a hydrogel with encapsulated cells at physiological body temperature. The objective of this work was to determine the effects of the hydrogel components on the phenotype of encapsulated chondrocytes. Bovine articular chondrocytes were used as an experimental model. Results demonstrated that the components required for hydrogel fabrication did not significantly reduce the proteoglycan synthesis of chondrocytes, a phenotypic marker of chondrocyte function. In addition, chondrocyte viability, proteoglycan synthesis, and type II collagen synthesis within P(PF-co-EG) hydrogels were investigated. The addition of bone morphogenetic protein-7 increased chondrocyte proliferation with the P(PF-co-EG) hydrogels, but did not increase proteoglycan synthesis by the chondrocytes. These results indicate that the temperatureresponsive P(PF-co-EG) hydrogels are suitable for chondrocyte delivery for articular cartilage repair.

Thermoresponsive hydrogels in biomedical applications

“…Moreover, the presence of the fumarate double bonds on PPF can allow for chemical crosslinking, enhancing thus the stability of the hydrogels. Recently, this hydrogel was evaluated for articular cartilage tissue engineering [76]. Chondrocytes were encapsulated in the hydrogel at 37°C and subsequently tested for their phenotypic characteristics.…”

Growth factor delivery-based tissue engineering: general approaches and a review of recent developments

“…The degradation of these polymers can be altered by changing the hydrophilicity through alteration of the chemical structure of the PNI-PAAM. In addition, most pH-sensitive materials mentioned above, including poly( propylene glycol) [160], poly( propylene fumarate) [161], poly(organophosphazenes) [162] and their derivatives, also show temperature-dependent gelation behaviours.…”

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

“…A vector of dependent variables {p} [1] is presented to a network of neurons [2] that each possesses a weight vector having the same number of components as the input vector {p}. The norm of the distance between the weight vector for each neuron and the input vector is then calculated (weighted input and net input), and a competitive transfer function [3] outputs 1 for the ''winning neuron,'' the neuron with the most positive net input. The neurons are then updated according to the Kohonen learning rule [4].…”

“…[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.…”