A pilot study of conically graded chitosan-gelatin hydrogel/PLGA scaffold with dual-delivery of TGF-beta 1 and BMP-2 for regeneration of cartilage-bone interface

摘要

Repair of cartilage-bone interface tissue remains challenging, because it combines different cell types and gradients of composition and properties. To enable simultaneous regeneration of bone, cartilage, and especially their interface, a conically graded scaffold of chitosan-gelatin hydrogel/poly(L-lactide-co-glycolide) (PLGA) was facilely prepared in the study. The chitosan-gelatin hydrogel containing transforming growth factor beta 1 (TGF-beta 1) was used for chondrogenesis, while the PLGA scaffold loading bone morphogenetic protein-2 (BMP-2) for osteogenesis. The conically graded transition from the hydrogel to PLGA scaffold and graded variation in amount of growth factors from TGF-b1 to BMP-2 benefited the cartilage-bone interface reconstruction. The graded scaffold exhibited spatio-temporal delivery of TGF-beta 1 and BMP-2. Preliminary results of in vitro cell culture demonstrated that the hydrogel and PLGA phases could promote bone marrow mesenchymal stem cells toward chondro-genic and osteogenic differentiation, respectively. From the result of the pilot in vivo experiment, it showed that the regenerated hyaline-like cartilage surface and subchondral bone excellently integrated with the native tissues were found by using the TGF-beta 1 and BMP-2 double-loaded hydrogel/PLGA graded scaffold via H&E and immunohistochemical stainings of collagen I, collagen II, and osteocalcin at 2 months. The obtained preliminary experiment results showed that the hydrogel/PLGA graded scaffold combining multiphasic composition and spatial dual growth-factor delivery would be useful for cartilage-bone interface tissue defect repair. (C) 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 1344-1353, 2015.