Controlled-release of IGF-I and TGF-beta1 in a photopolymerizing hydrogel for cartilage tissue engineering.
Photopolymerizing hydrogel systems provide a method to encapsulate cells and implant materials in a minimally invasive manner. Controlled release of growth factors in the hydrogels may enhance the ability to engineer tissues. IGF-I and TGF-beta1 were loaded in PLGA microspheres using a double emulsion technique. 125 ng and 200 pg of active IGF-I and TGF-beta, respectively, as measured by ELISA, were released over 15 days. The growth factor containing microspheres were photoencapsulated with bovine articular chondrocytes in PEO-based hydrogels and incubated in vitro for two weeks. Statistically significant changes in glycosaminoglycan (GAG) production compared to control gels either without microspheres or with blank spheres were observed after a 14 day incubation with IGF-I and IGF-I/TGF-beta microspheres combined, with a maximum density of 8.41+/-2.5% wet weight GAG. Total collagen density was low and decreased with the IGF-I/TGF-beta microspheres after two weeks incubation, but otherwise remained unchanged in all other experimental groups. Cell content increased 10-fold to 0.18+/-0.056 x 10(6) cells/mg wet weight and extracellular matrix (ECM) staining by H&E increased in hydrogels with IGF-I/TGF-beta microspheres. In conclusion, photoencapsulation of microspheres in PEO-based hydrogels provides a method to deliver molecules such as growth factors in porous hydrogel systems.
Elisseeff
J
J
Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA.
McIntosh
W
W
Fu
K
K
Blunk
B T
BT
Langer
R
R
D000818:Animals; D002356:Cartilage / Q000187:drug effects*; D002417:Cattle; D019902:Chondrocytes / Q000187:drug effects; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage*; D019344:Lactic Acid / Q000008:administration & dosage; D008863:Microspheres; D011100:Polyglycolic Acid / Q000008:administration & dosage; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage; D023822:Tissue Engineering; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*
D011108:Polymers; D016212:Transforming Growth Factor beta; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007334:Insulin-Like Growth Factor I