title: Fetal dermal fibroblasts exhibit enhanced growth and collagen production in two- and three-dimensional culture in comparison to adult fibroblasts.
abstract: The high morbidity of tendon injuries and the poor outcomes observed following repair or replacement have stimulated interest in regenerative approaches to treatment and, in particular, the use of cell-based analogues as alternatives to autologous and allogeneic graft repair. Given the known regenerative properties of fetal tissues, the objective of this study was to assess the biological and mechanical properties of tissue-engineered three-dimensional (3D) composites seeded with fetal skin cells. Dermal fibroblasts were isolated from pregnant rats and their fetuses and characterized in monolayer culture and on 3D resorbable polyester scaffolds. To determine the differences between fetal and adult fibroblasts, DNA, total protein and types I and III collagen production were measured. In addition, morphology and mechanical properties of the 3D constructs were examined. In monolayer culture, fetal fibroblasts produced significantly more types I and III collagen and displayed serum-independent growth, while adult fibroblasts elaborated less collagen and exhibited reduced cell spreading and attachment under low-serum conditions. In 3D culture, fetal constructs appeared more developed based on gross examination, with significantly more total DNA, total protein and normalized type I collagen production compared to adult specimens. Finally, after 35 days, fetal fibroblast-seeded constructs possessed superior mechanical properties compared to adult samples. Taken together, these findings indicate that fetal dermal fibroblasts may be an effective source of cells for fabricating tissue equivalents to regenerate injured tendons.
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Hallie E
authors.initials: HE
authors.lastname: Brink
authors.forename: Joseph
authors.initials: J
authors.lastname: Bernstein
authors.forename: Steven B
authors.initials: SB
authors.lastname: Nicoll
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured / Q000166:cytology*; D003094:Collagen / Q000378:metabolism*; D024042:Collagen Type I / Q000737:chemistry; D024061:Collagen Type III / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry / Q000379:methods; D011091:Polyesters / Q000737:chemistry; D051381:Rats; D012867:Skin / Q000196:embryology*; D014945:Wound Healing
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D011091:Polyesters; D003094:Collagen; D004247:DNA