Injectable Tissue-Engineered Cartilage with Different Chondrocyte Sources

Abstract

Injectable engineered cartilage that maintains a predictable shape and volume would allow recontouring of craniomaxillofacial irregularities with minimally invasive techniques. This study investigated how chondrocytes from different cartilage sources, encapsulated in fibrin polymer, affected construct mass and volume with time. Swine auricular, costal, and articular chondrocytes were isolated and mixed with fibrin polymer (cell concentration of 40 x 10 cells/ml for all groups). Eight samples (1 cm x 1 cm x 0.3 cm) per group were implanted into nude mice for each time period (4, 8, and 12 weeks). The dimensions and mass of each specimen were recorded before implantation and after explantation. Ratios comparing final measurements and original measurements were calculated. Histological, biochemical, and biomechanical analyses were performed. Histological evaluations (n = 3) indicated that new cartilaginous matrix was synthesized by the transplanted chondrocytes in all experimental groups. At 12 weeks, the ratios of dimension and mass (n = 8) for auricular chondrocyte constructs increased by 20 to 30 percent, the ratios for costal chondrocyte constructs were equal to the initial values, and the ratios for articular chondrocyte constructs decreased by 40 to 50 percent. Constructs made with auricular chondrocytes had the highest modulus (n = 3 to 5) and glycosaminoglycan content (n = 4 or 5) and the lowest permeability value (n = 3 to 5) and water content (n = 4 or 5). Constructs made with articular chondrocytes had the lowest modulus and glycosaminoglycan content and the highest permeability value and water content (p < 0.05). The amounts of hydroxyproline (n = 5) and DNA (n = 5) were not significantly different among the experimental groups (p > 0.05). It was possible to engineer injectable cartilage with chondrocytes from different sources, resulting in neocartilage with different properties. Although cartilage made with articular chondrocytes shrank and cartilage made with auricular chondrocytes overgrew, the injectable tissue-engineered cartilage made with costal chondrocytes was stable during the time periods studied. Furthermore, the biomechanical properties of the engineered cartilage made with auricular or costal chondrocytes were superior to those of cartilage made with articular chondrocytes, in this model.

Hydrogels for the Repair of Articular Cartilage Defects

“…206,207 Auricular chondrocytes encapsulated in hyaluronic acid or fibrin hydrogels experienced increased ECM production and mechanical properties compared to articular chondrocytes after 12 weeks of subcutaneous implantation. 208,209 However, articular chondrocytes upregulated expression of type II collagen and aggrecan to greater extents in response to stimulation by dynamic loading. 208 In another study, the potential of chondrocytes suspended in fibrin gels to integrate with native articular cartilage did not depend on the source of the chondrocytes.…”

Long-Term Morphological and Microarchitectural Stability of Tissue-Engineered, Patient-Specific AuriclesIn Vivo

“…However, the degradation of these polymers has been reported to cause inflammatory reactions. 3,4 Natural polymer scaffolds and hydrogels, such as alginate 13 and fibrin, 14 are easily molded and have high biocompatibility, 4 but are limited by low stiffness, making them difficult to handle. 15 Chondrocytes encapsulated in alginate and then implanted also become fibrochondrogenic.…”

“…Few groups have worked with methods that can apply patient-specific morphologies to engineered ear constructs, 19,20 resulting in generic ears that must be surgically manipulated to reproduce particular aesthetics. Additionally, the maintenance of ear morphology following implantation often requires mechanical assistance, either through external stenting over the skin 14 or internal plastic 21 or metal 10,[22][23][24] support that is included with the implant. Our group has previously applied digital photogrammetry and computer-assisted design/computer-aided manufacturing (CAD/CAM) techniques to fabricate molds replicating juvenile patient ears, a novel technique to recreate specific ear morphology.…”

Characterization of auricular chondrocytes and auricular/articular chondrocyte co-cultures in terms of an application in articular cartilage repair

“…Three independent experiments using chondrocytes from 3 different donors are included. made with articular chondrocytes as reported by Xu et al (29).…”