Controlled release of TGF-beta 1 from a biodegradable matrix for bone regeneration.
Although bone has a remarkable capacity for regenerative growth, there are many clinical situations in which the bony repair process is impaired. TGF-beta 1 is a 25 kD homodimeric protein which modulates the growth and differentiation of many cell types. The ability of TGF-beta 1 to promote bone formation suggests that it may have potential as a therapeutic agent in disease of bone loss. However, there still exists a need for an effective method of delivering TGF-beta 1 to the site of an osseous defect for the promotion of bone healing. This paper describes a novel biodegradable controlled release system for TGF-beta 1 comprised of poly (DL-lactic-co-glycolic acid) (PLPG) and demineralized bone matrix (DBM). The amount and activity of TGF-beta 1 released was determined using several methods including 125I-labeled TGF-beta 1 as a tracer, an enzyme linked immunosorbent assay (ELISA) and a growth inhibitory assay (GIA). Protein was released from the devices for time periods of more than 600 h. The amount of TGF-beta 1 released was directly proportional to both the TGF-beta 1 loading and the weight percent of DBM in the device. The release kinetics could be further controlled by applying polymeric coatings of varying porosity to the devices. The GIA indicated that between 80 and 90% of the TGF-beta 1 released from the delivery system retained its bioactivity. The PLPG and DBM existed in phase separated domains within the device as determined by differential scanning calorimetry. Scanning electron microscopy suggested that the devices were sufficiently porous to allow bone ingrowth.
Gombotz
W R
WR
Bristol-Myers Squibb, Pharmaceutical Research Institute, Seattle, WA 98121.
Pankey
S C
SC
Bouchard
L S
LS
Ranchalis
J
J
Puolakkainen
P
P
D000818:Animals; D001672:Biocompatible Materials; D001857:Bone Matrix / Q000187:drug effects / Q000502:physiology*; D001842:Bone and Bones / Q000187:drug effects / Q000502:physiology*; D003692:Delayed-Action Preparations; D019344:Lactic Acid; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011817:Rabbits; D012038:Regeneration / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000494:pharmacology
D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D011108:Polymers; D016212:Transforming Growth Factor beta; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid