Use of recombinant human osteogenic protein-1 for the repair of subchondral defects in articular cartilage in goats

Abstract

The objective of this pilot study was to examine in vivo the potential of recombinant human osteogenic protein-1 (rhOP-1, also called bone morphogenetic protein-7, BMP-7) for treatment of subchondral lesions by induction of new hyaline cartilage formation. Subchondral left knee defects in 17 mature goats were treated with fresh coagulated blood mixed with (1) rhOP-1 combined with collagen (OP-1 device, 400 microgram/mL); (2) rhOP-1 alone (OP-1 peptide, 200 microgram/mL); (3) OP-1 device with small particles of autologous ear perichondrium; (4) OP-1 peptide with small particles of autologous ear perichondrium; or (5) autologous ear perichondrium alone (controls). rhOP-1 was combined with either collagen (OP-1 device) or not (OP-1 peptide). The defects were closed with a periosteal flap. The formation of cartilage tissue was studied by histologic and biochemical evaluation at 1, 2, and 4 months after implantation. One and 2 months after implantation there were no obvious differences between control and rhOP-1-treated defects. Four months after implantation, only one out of three controls (without rhOP-1) showed beginning signs of cartilage formation while all four rhOP-1-treated defects were completely or partly filled with cartilage. A significant linear relationship was found between rhOP-1 concentration and the total amount of aggrecan in the defects. These results suggest that implantation of rhOP-1 promotes cartilage formation in subchondral defects in goats at 4 months after implantation. Therefore, rhOP-1 could be a novel factor for regeneration of cartilage in articular cartilage defects.

Safety of, and biological and functional response to, a novel metallic implant for the management of focal full‐thickness cartilage defects: Preliminary assessment in an animal model out to 1 year

“…29 In other reported studies, untreated full-thickness defects with diameters of 4 to 10 mm healed with biomechanically inferior fibrous or fibrocartilagenous tissue covering the defect, frequently with fissuring towards its center and, in some examples, cartilage matrix flow covering the defect periphery. [30][31][32][33][34] The outcome in our goats was, by comparison, substantially better. First, the congruency between the surface implant and adjacent cartilage, as well as the device's accurate replication of the articular contour, provided an effective weight-bearing continuum across the MFC, reflected in the generally balanced increase in bone modeling and remodeling noted around the surface and anchoring components of the prostheses.…”

“…Although focal articular changes were documented in operated joints, the pathology was much reduced over that encountered in previous caprine osteochondral defect studies. [30][31][32][33][34] Expanded preclinical or clinical human studies are justified.…”

The effect of recombinant human osteogenic protein-1 on growth plate repair in a sheep model

“…This dosage was the same as that used in the study by Johnstone et al [17], which reported an increase in growth plate height adjacent to the defect. This dosage is within the range of that used in other in vivo studies to regenerate articular and thyroid cartilages, doses of which have ranged from 11 pg to 500 pg f4, 16,18,24]. All of these studies have reported an induction of chondrogenesis, with cells taking on the chondrocyte phenotype and producing cartilage specific collagens and proteoglycans.…”

“…In addition to its powerful bone healing properties, the chondrogenic potential of OP-1 has been 0736 well documented [3,4,6,11,15,16,24]. In vitro studies in rat calvarial cells, ATDC5 cells, mouse embryonic long bone cultures, transplanted perichondrial cultures and articular cartilage cultures have reported an increase in the synthesis of type I1 collagen and proteoglycans following the administration of recombinant human OP-1 (rhOP-I); [l-3,5,6,13,19,20].…”

“…The repair of articular cartilage defects in vivo using rhOP-1 has been reported in rabbits, goats, sheep and dogs [4,11,16,24,25]. The defect is repaired through the infiltration of mesenchymal cells that differentiate into cells resembling articular cartilage chondrocytes.…”