Lee K. Landeen

A three-dimensional osteochondral composite scaffold for articular cartilage repair

There is a recognized and urgent need for improved treatment of articular cartilage defects. Tissue engineering of cartilage using a cell-scaffold approach has demonstrated potential to offer an alternative and effective method for treating articular defects. We have developed a unique, heterogeneous, osteochondral scaffold using the TheriForm three-dimensional printing process. The material composition, porosity, macroarchitecture, and mechanical properties varied throughout the scaffold structure. The upper, cartilage region was 90% porous and composed of D,L-PLGA/L-PLA, with macroscopic staggered channels to facilitate homogenous cell seeding. The lower, cloverleaf-shaped bone portion was 55% porous and consisted of a L-PLGA/TCP composite, designed to maximize bone ingrowth while maintaining critical mechanical properties. The transition region between these two sections contained a gradient of materials and porosity to prevent delamination. Chondrocytes preferentially attached to the cartilage portion of the device, and biochemical and histological analyses showed that cartilage formed during a 6-week in vitro culture period. The tensile strength of the bone region was similar in magnitude to fresh cancellous human bone, suggesting that these scaffolds have desirable mechanical properties for in vivo applications, including full joint replacement.

Tissue-Engineered, Three-Dimensional Human Dermis to Study Extracellular Matrix Formation in Wound Healing

AbstractA human dermal model consisting of neonatal dermal fibroblasts grown on nylon mesh was used to study extracellular matrix (ECM) formation. The fibroblasts deposit ECM, forming a three-dimensional, tissue-like structure consisting of collagen types I and III, fibronectin, tenascin, and decorin. This model was compared with fetal, neonatal, and adult human dermis and was found to be most similar to fetal dermis.To determine keratinocyte-mediated effects on the dermal ECM, the dermal model was cocultured with human neonatal foreskin keratinocytes. Fibronectin synthesis and deposition were examined by in situ hybridization and indirect immunofluorescence, respectively. After 2 weeks, fibronectin deposition throughout the dermis had increased compared with dermal cultures incubated in the absence of keratinocytes, indicating that keratinocytes influenced net fibronectin deposition. As measured by in situ hybridization, fibronectin mRNA increased after coculture with keratinocytes, with maximal signal d...