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Biomedical subjects

John M Mesa

Publications and source records attributed to John M Mesa.

3 recordsLinked to original sources

Tissue engineering cartilage with aged articular chondrocytes in vivo.

BACKGROUND: Tissue engineering has the potential to repair cartilage structures in middle-aged and elderly patients using their own "aged" cartilage tissue as a source of reparative chondrocytes. However, most studies on tissue-engineered cartilage have used chondrocytes from postfetal or very young donors. The authors hypothesized that articular chondrocytes isolated from old animals could produce neocartilage in vivo as well as articular chondrocytes from young donors. METHODS: Articular chondrocytes from 8-year-old sheep (old donors) and 3- to 6-month-old sheep (young donors) were isolated. Cells were mixed in fibrin gel polymer at 40 x 10 cells/ml until polymerization. Cell-polymer constructs were implanted into the subcutaneous tissue of nude mice and harvested at 7 and 12 weeks. RESULTS: Samples and native articular cartilage controls were examined histologically and assessed biochemically for total DNA, glycosaminoglycan, and hydroxyproline content. Histological analysis showed that samples made with chondrocytes from old donors accumulated basophilic extracellular matrix and sulfated glycosaminoglycans around the cells in a manner similar to that seen in samples made with chondrocytes from young donors at 7 and 12 weeks. Biochemical analysis revealed that DNA, glycosaminoglycan, and hydroxyproline content increased in chondrocytes from old donors over time in a pattern similar to that seen with chondrocytes from young donors. CONCLUSIONS: This study demonstrates that chondrocytes from old donors can be rejuvenated and can produce neocartilage just as chondrocytes from young donors do when encapsulated in fibrin gel polymer in vivo. This study suggests that middle-aged and elderly patients could benefit from cartilage tissue-engineering repair using their own "aged" articular cartilage as a source of reparative chondrocytes.

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Injectable tissue-engineered cartilage with different chondrocyte sources.

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.

Animals↗

Integrative repair of cartilage with articular and nonarticular chondrocytes.

Articular chondrocytes can synthesize new cartilaginous matrix in vivo that forms functional bonds with native cartilage. Other sources of chondrocytes may have a similar ability to form new cartilage with healing capacity. This study evaluates the ability of various chondrocyte sources to produce new cartilaginous matrix in vivo and to form functional bonds with native cartilage. Disks of articular cartilage and articular, auricular, and costal chondrocytes were harvested from swine. Articular, auricular, or costal chondrocytes suspended in fibrin glue (experimental), or fibrin glue alone (control), were placed between disks of articular cartilage, forming trilayer constructs, and implanted subcutaneously into nude mice for 6 and 12 weeks. Specimens were evaluated for neocartilage production and integration into native cartilage with histological and biomechanical analysis. New matrix was formed in all experimental samples, consisting mostly of neocartilage integrating with the cartilage disks. Control samples developed fibrous tissue without evidence of neocartilage. Ultimate tensile strength values for experimental samples were significantly increased (p < 0.05) from 6 to 12 weeks, and at 12 weeks they were significantly greater (p < 0.05) than those of controls. We conclude that articular, auricular, and costal chondrocytes have a similar ability to produce new cartilaginous matrix in vivo that forms mechanically functional bonds with native cartilage.

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