The effect of a slow mode of BMP-2 delivery on the inflammatory response provoked by bone-defect-filling polymeric scaffolds.
We investigated the inflammatory response to, and the osteoinductive efficacies of, four polymers (collagen, Ethisorb, PLGA and Polyactive) that bore either an adsorbed (fast-release kinetics) or a calcium-phosphate-coating-incorporated (slow-release kinetics) depot of BMP-2. Titanium-plate-supported discs of each polymer (n = 6 per group) were implanted at an ectopic (subcutaneous) ossification site in rats (n = 48). Five weeks later, they were retrieved for a histomorphometric analysis of the volumes of ectopic bone and foreign-body giant cells (a gauge of inflammatory reactivity), and the degree of polymer degradation. For each polymer, the osteoinductive efficacy of BMP-2 was higher when it was incorporated into a coating than when it was directly adsorbed onto the material. This mode of BMP-2 carriage was consistently associated with an attenuation of the inflammatory response. For coated materials, the volume density of foreign-body giant cells was inversely correlated with the volume density of bone (r(2) = 0.96), and the volume density of bone was directly proportional to the surface-area density of the polymer (r(2) = 0.97). Following coating degradation, other competitive factors, such as the biocompatibility and the biodegradability of the polymer itself, came into play.
Wu
Gang
G
Center of Regenerative Medicine for Skeletal Tissues, Department of Clinical Research, University of Bern, Murtenstrasse 35, CH-3010 Bern, Switzerland.
Liu
Yuelian
Y
Iizuka
Tateyuki
T
Hunziker
Ernst Bruno
EB
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001842:Bone and Bones / Q000187:drug effects / Q000276:immunology*; D003094:Collagen / Q000009:adverse effects / Q000737:chemistry; D015743:Giant Cells, Foreign-Body / Q000187:drug effects / Q000378:metabolism; D019344:Lactic Acid / Q000009:adverse effects / Q000737:chemistry; D010012:Osteogenesis / Q000187:drug effects; D011091:Polyesters / Q000009:adverse effects / Q000737:chemistry; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000737:chemistry; D011100:Polyglycolic Acid / Q000009:adverse effects / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000009:adverse effects* / Q000737:chemistry; D051381:Rats; D054457:Tissue Scaffolds / Q000009:adverse effects* / Q000737:chemistry*
D055396:Bone Morphogenetic Protein 2; C460779:Ethisorb; D011091:Polyesters; D011108:Polymers; C072932:polyethylene oxide-polybutylene terephthalate copolymer; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D003094:Collagen