Porous chitosan-gelatin scaffold containing plasmid DNA encoding transforming growth factor-beta1 for chondrocytes proliferation.
Cartilage defects as a result of disease or injury have a very limited ability to heal spontaneously. Recently, tissue engineering and local therapeutic gene delivery systems have been paid much attention in the cartilage natural healing process. Gene-activated matrix (GAM) blends these two strategies, serving as local bioreactor with therapeutic agents expression and also providing a structural template to fill the lesion defects for cell adhesion, proliferation and synthesis of extracellular matrix (ECM). In the current study, we used chitosan-gelatin complex as biomaterials to fabricate three-dimensional scaffolds and plasmid DNA were entrapped in the scaffolds encoding transforming growth factor-beta1 (TGF-beta1), which has been proposed as a promoter of cartilage regeneration for its effect on the synthesis of matrix molecules and cell proliferation. The plasmid DNA incorporated in the scaffolds showed a burst release in the first week and a sustained release for the other 2 weeks. The gene transfectd into chondrocytes expresses TGF-beta1 protein stably in 3 weeks. The histological and immunohistochemical results confirmed that the primary chondrocytes cultured into the chitosan-gelatin scaffold maintained round and owned characters of high secretion of specific ECM. From this study, it can be concluded that this gene-activated chitosan-gelatins matrix has a potential in the application of cartilage defects regeneration.
Guo
Ting
T
State Key Laboratory of Pharmaceutical Biotechnology, Department of Biochemistry, Nanjing University, Nanjing 210093, PR China.
Zhao
Jianning
J
Chang
Jianbin
J
Ding
Zhi
Z
Hong
Hao
H
Chen
Jiangning
J
Zhang
Junfeng
J
D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry*; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology*; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry; D005780:Gelatin / Q000737:chemistry*; D018014:Gene Transfer Techniques; D006801:Humans; D008422:Materials Testing; D010957:Plasmids / Q000008:administration & dosage* / Q000737:chemistry*; D016062:Porosity; D011506:Proteins / Q000737:chemistry*; D011817:Rabbits
D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D011506:Proteins; D005780:Gelatin; D048271:Chitosan