Faculty Bibliography

The purpose of this study was to observe the difference in healing of full-thickness articular cartilage defects treated with burr arthroplasty versus subchondral drilling. Cartilage was shaved off the medial femoral condyles of 39 rabbits without penetrating the subchondral plate. In left knees, two 2.0-mm holes were drilled into the condyle until bleeding was obtained. Right knees underwent a burr arthroplasty until punctate bleeding was observed. Animals were sacrificed at 6, 12, and 24 weeks postoperatively. Joint resurfacing and degenerative changes were evaluated grossly and histologically. Degenerative changes in the cartilage surface were observed with both treatments. Rabbits undergoing subchondral drilling had increased fibrocartilaginous healing with time, with a slight increase in degenerative changes. With burr arthroplasty, there was significant decrease in cartilaginous coverage of the exposed surface as well as progressive increase in degenerative changes. Although both techniques were suboptimal, histological evidence at 6 months suggests that subchondral drilling may result in a longer-lived repair than abrasion arthroplasty in the treatment of full-thickness lesions

The effects of incubation and addition of growth factors to a chondrocyte-seeded collagen implant for cartilage repair were studied. Type I collagen matrices seeded with lapine articular chondrocytes and unseeded controls cultured in the presence and absence of fibroblast growth factor and insulin for 2, 6, and 9 weeks were subjected to biomechanical, biochemical, and histological analysis. Aggregate modulus of elasticity of seeded implants decreased by half at 6 weeks, then rose by a factor of 10 above initial values. Permeability of seeded implants and their controls decreased steadily. Glycosaminoglycan content peaked at 6 weeks, coinciding with the greatest number of chondrocytes and mitotic activity in seeded implants. Chondrocytes remained phenotypically stable and metabolically active; they incorporated glycosaminoglycan into the extracellular matrix, and formed an organized pericellular environment despite the predicted resorption of the collagen matrix. Adding fibroblast growth factor and insulin tripled the rate of cell turnover and doubled the glycosaminoglycan content of seeded implants, but had no effect on their material properties. In vitro incubation for 6 weeks in the presence of fibroblast growth factor and insulin creates a metabolically and mitotically active chondrocyte-collagen composite for implantation into articular cartilage defects

A study was conducted to determine the ability of demineralized bone matrix gel to act as an osteoconductive/osteoinductive material to enhance canine spinal fusion. Seven dogs underwent posterior spinal fusion. Four-level fusions were performed with one of four procedures at each level: decortication alone, with gel added, with autograft, or with both gel and autograft. Dogs were killed at 6 weeks and early histologic response was studied. At untreated control sites, little bone formation was evident. Gel-filled sites showed abundant osteoid, with 60% of demineralized particles fused to or surrounded by new bone. Sites filled with autograft had more new bone, but there was more osteoid at gel-treated sites. Autograft augmented with gel showed the most vigorous response, with extensive bridging between demineralized particles, host bone, autograft, and new bone. Significantly less autograft was needed to induce a similar amount of new bone formation when gel was added. Use of the gel as an autograft extender may improve the chance for successful spinal fusion

Fibroblast growth factor (FGF) is a polypeptide that has been shown to have a stimulatory effect on osseous tissues in vitro. This study characterized the release of FGF from plaster of Paris (PLP) and measured the dissolution of PLP in various solutions with the aim of developing a reliable carrier system for the release of FGF in vivo. The study consisted of five experiments: (I) FGF diffusion from PLP pellets, (II) FGF diffusion from PLP discs, (III) PLP dissolution in saline, (IV) PLP dissolution in serum, and (V) FGF adsorption by commercially pure titanium. FGF was observed to be released at a rate directly proportional to the rate of dissolution of the PLP carrier, suggesting that either the FGF binds to the PLP; or, alternatively, the FGF may be entrapped by the PLP. Dissolution rate, and thus release rate, could be varied by varying the mass of the carrier. Greater diffusion of FGF was observed in larger, more slowly dissolving PLP carriers. Dissolution of PLP was observed to be slower in serum than in saline, apparently due to stabilization by factors in the serum but not due to a concentration gradient effect. Titanium coupons did not adsorb significant amounts of FGF. These results indicate that PLP, which has been shown in the past neither to aggravate inflammatory response nor to interfere with bone ingrowth, may serve as delivery vehicle for FGF to osseous tissues in vivo

In vivo effects of fibroblast growth factor (FGF) on osteogenesis were evaluated in the chick embryo. Autoradiographic studies of 3H-proline labeling over bone matrix indicated that 24 h after treatment on day 11, FGF stimulated osteogenic cell proliferation, while inhibiting the production of bone matrix collagen. However, 4 days after multiple doses of FGF, the large pool of newly formed osteogenic and chondrogenic cells expressed their function with the increased formation of matrix. The data provide in vivo evidence of the effects of exogenous FGF on osteogenesis and also point to a possible role for FGF both in embryonic osteogenesis and in fracture repair

In vivo effects of FGF on osteogenesis in the chick embryo were evaluated. Day-11 embryos were injected with FGF followed by radiotracers. 3H-thymidine labelling of osteogenic cells was significantly higher following FGF administration; 3H-proline labelling over bone matrix was greater in the controls. Cartilage cells and matrix were sparsely labelled indicating a low level of metabolic activity. These data provide the first in vivo evidence that FGF stimulates osteogenic cell proliferation, while inhibiting production of bone matrix collagen. A role for FGF in embryonic osteogenesis and in fracture repair is suggested

This study demonstrates, via immunohistochemistry and bioassay, the presence of NGF in embryonic bone and cartilage of the chick. Embryos were killed on days 6-9 of incubation at 12 h intervals, and on days 10-18 at 24 h intervals. Paraffin-embedded sections of hind limbs or buds were immunostained with a polyclonal antibody against NGF and the biotin-avidin-horseradish peroxidase technique. Immunostaining was positive in both bone and cartilage, with cartilage staining more intensely. For bioassay, bones from the hind limbs of 9- and 12-day embryos were fast-frozen, lyophilized, and homogenized with Medium 199 (M199). Dorsal root ganglia from 8-day embryos were cultured for 24-36 h with rooster plasma, M199, and varying concentrations of bone homogenate. Significant neurite outgrowth was seen, with the greatest response elicited by 12-day bone homogenate. Addition of anti-NGF to the cultures abolished neurite outgrowth. The results indicate that NGF is present in cartilage and bone of the chick embryo; it may determine the density of sympathetic innervation to the developing skeletal tissues.