RESUMEN
In this study, we evaluate a porous polylactic acid-polyglycolic acid (PLGA) polymer in tissue engineering a small hand phalanx. The PLGA polymer was processed with a unique solvent cast/salt-leaching method in the shape of a little finger distal phalanx. An 85% polylactic acid (PLA)/15% polyglycolic acid (PGA) copolymer was determined to be the most favorable mixture for creating a small digital phalanx in precise shape and size. The pore sizes averaged 250-425 microm. Bovine periosteum was wrapped around each phalangeal polymer. Chondrocytes were injected into the articular end. Six constructs were surgically placed into a dorsal subcutaneous pocket of an ethylic mouse. After 8 (n=2) or 16 (n = 4) weeks, all implants demonstrated growth of bone and cartilage in the shape and size of a small hand phalanx, which was maintained throughout the study period. Histologic evaluation showed a homogeneous presence of bone and cartilage, with progressive tissue differentiation and matrix production from 8 to 16 weeks. The tissue-engineered bone formed through an endochondral ossification process. Articular cartilage was maintained where the chondrocytes were placed. These findings suggest that the porous PLGA polymer is an effective synthetic biodegradable device to support and guide tissue growth of bone and articular cartilage in the shape of a human phalanx.
Asunto(s)
Implantes Absorbibles , Bioprótesis , Condrocitos/fisiología , Falanges de los Dedos de la Mano , Ácido Láctico , Osteogénesis/fisiología , Periostio/fisiología , Ácido Poliglicólico , Polímeros , Animales , Sustitutos de Huesos , Cartílago Articular/citología , Cartílago Articular/fisiología , Bovinos , Células Cultivadas , Condrocitos/citología , Humanos , Ácido Láctico/química , Periostio/citología , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Polímeros/química , Ingeniería de Tejidos/métodosRESUMEN
Non-viral gene vectors are commonly used for gene therapy owing to safety concerns with viral vectors. However, non-viral vectors are plagued by low levels of gene transfection and cellular expression. Current efforts to improve the efficiency of non-viral gene delivery are focused on manipulations of the delivery vector, whereas the influence of the cellular environment in DNA uptake is often ignored. The mechanical properties (for example, rigidity) of the substrate to which a cell adheres have been found to mediate many aspects of cell function including proliferation, migration and differentiation, and this suggests that the mechanics of the adhesion substrate may regulate a cell's ability to uptake exogeneous signalling molecules. In this report, we present a critical role for the rigidity of the cell adhesion substrate on the level of gene transfer and expression. The mechanism relates to material control over cell proliferation, and was investigated using a fluorescent resonance energy transfer (FRET) technique. This study provides a new material-based control point for non-viral gene therapy.