Abstract
This study explores the suitability of using encapsulated geneticallymodified fibroblasts for orthopedic tissue engineering by examining cell survival and persistence of human transforming growth factor-β (hTGF-β) overexpression in xenogeneic and allogeneic implant models. Human wild-type fibroblasts, modified to produce a latent form of hTGF-β, and murine mutant-type fibroblasts, engineered to release a constitutively active form of hTGF-β, were encapsulated separately in Ca2+—alginate microcapsules. Following a percentage viability assessment by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) test, microcapsules were implanted into either the subcutaneous or intraperitoneal cavities of mice. Explanted encapsulated cells were characterized for percentage viability and subjected to a release study and a viability test 1 week and 3 weeks following implantation, a time frame consistent with the requirement for orthopedic tissue engineering application of this growth factor. On average, percentage viabilities of encapsulated cells were 64%at implantation, 52% at explantation, and 56%after 1 week following either 1- or 3-week explantation. hTGF-β release declined following in vivo implantation, more so for xenogeneic than allogeneicmodels, but remained in the clinically attractive range of 2 to 30 ng/(106 implanted cells 24 h). This technical platform for hTGF-β is very encouraging for cartilage regeneration using orthopedic tissue engineering, and further evaluation is warranted.
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