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Biomedical subjects

R D Coutts

Publications and source records attributed to R D Coutts.

At least 19 recordsLinked to original sources
PubMed2005

Regeneration of articular cartilage--evaluation of osteochondral defect repair in the rabbit using multiphasic implants.

OBJECTIVE: To investigate whether two different multiphasic implants could initiate and sustain repair of osteochondral defects in rabbits. The implants address the malleable properties of cartilage while also addressing the rigid characteristics of subchondral bone. DESIGN: The bone region of both devices consisted of D, D-L, L-polylactic acid invested with hyaluronan (HY). The cartilage region of the first device was a polyelectrolytic complex (PEC) hydrogel of HY and chitosan. In the second device the cartilage region consisted of type I collagen scaffold. Eighteen rabbits were implanted bilaterally with a device, or underwent defect creation with no implant. At 24 weeks, regenerated tissues were evaluated grossly, histologically and via immunostaining for type II collagen. RESULTS: PEC devices induced a significantly better repair than untreated shams. Collagen devices resulted in a quality of repair close to that of the PEC group, although its mean repair score (19.0+/-4.2) did not differ significantly from that of the PEC group (20.4+/-3.7) or the shams (16.5+/-6.3). The percentage of hyaline-appearing cartilage in the repair was highest with collagen implants, while the degree of bonding of repair to the host, structural integrity of the neocartilage, and reconstitution of the subchondral bone was greatest with PEC devices. Cartilage in both device-treated sites stained positive for type II collagen and GAG. CONCLUSIONS: Both implants are capable of maintaining hyaline-appearing tissue at 24 weeks. The physicochemical region between the cartilage and bone compartments makes these devices well suited for delivery of different growth factors or drugs in each compartment, or different doses of the same factor. It also renders these devices excellent vehicles for chondrocyte or stem cell transplantation.

Animals↗
PubMed2002

Development and regulation of osteophyte formation during experimental osteoarthritis.

OBJECTIVES: Osteophytes represent areas of new cartilage and bone formation in human and experimentally induced osteoarthritis (OA). The present study addressed the production of nitric oxide (NO), vascular endothelial growth factor (VEGF) and the occurrence of apoptosis during osteophyte formation. DESIGN: Osteophytes in the knee joint of rabbits that developed OA-like lesions following anterior cruciate ligament transection (ACLT) were analysed by histology and immunohistochemistry for NO production, and the presence of VEGF. TUNEL was used to detect DNA fragmentation. RESULTS: At the joint margins in the interface between cortical bone marrow and periosteal lining growth plate-like formations were detectable as early as 4 weeks after ACLT. By 12 weeks after ACLT osteophytes were visible in 100% of femoral condyles and tibial plateaus. Discrete areas with proliferating chondrocytes, hypertrophic chondrocytes, calcified matrix and vascular invasion were observed. VEGF immunoreactivity was most prominent in hypertrophic chondrocytes 9 weeks after ACLT. Nitrotyrosine immunoreactivity was detected in endothelial cells and in some hypertrophic chondrocytes in the calcified zone 4 weeks after ACLT. After 8 and 12 weeks, positive cells were detected in the hypertrophic and calcified zone. TUNEL-positive cells were seen in blood vessels, and among hypertrophic chondrocytes adjacent to the blood vessels 4 weeks after ACLT. The proliferative zone, pre-hypertrophic zone and hypertrophic zone showed only a few TUNEL positive cells. In contrast, 8 weeks and 12 weeks after ACLT, most hypertrophic chondrocytes, but few proliferative chondrocytes showed DNA fragmentation. CONCLUSIONS: Hypertrophic chondrocytes in osteophytes express VEGF and this can promote vascular invasion of cartilage. The presence of TUNEL-positive cells shows a similar distribution as nitrotyrosine immunoreactivity during all phases of osteophyte development, suggesting that NO production and chondrocyte death are related events in osteophyte formation.

Animals↗
PubMed2001

Recurrent dislocation after total hip arthroplasty: treatment with an Achilles tendon allograft.

Surgical treatment of recurrent dislocation after total hip arthroplasty (THA) is challenging with often disappointing results. Among possible causes of dislocation, the influence of the static soft tissue restraint provided by the hip capsule is important, and restoration of its integrity and function is a major goal of treatment. We describe a new technique in which an Achilles tendon allograft is employed as a checkrein to limit hip internal rotation and to prevent posterior instability. Ten unstable THAs were treated using this technique, eliminating instability in 6. At an average follow-up of 3 years, Achilles tendon allograft augmentation has proved to be a useful adjunct for the treatment of recurrent posterior dislocation after THA in selected patients.

Achilles Tendon↗
PubMed2001

The increasing need for nonoperative treatment of patients with osteoarthritis.

Osteoarthritis affects more patients than almost any other musculoskeletal disorder. The number of patients suffering joint pain and stiffness as a result of this disease will increase rapidly in the next decade. Although operative treatments of patients with osteoarthritis will continue to improve and the number of operative procedures will increase slightly in the next decade, only a small fraction of the patients with osteoarthritis will require operative procedures. The most pressing healthcare need for the majority of patients with osteoarthritis is nonoperative care that helps relieve symptoms and improve function, and in some instances slows progression. In rare instances, the symptoms of osteoarthritis improve spontaneously, but most patients need nonoperative care for decades. Orthopaedists need to improve their ability to provide nonoperative care for patients with osteoarthritis. They should be skilled in the early diagnosis of osteoarthritis and in the use of current common nonoperative treatments including patient education, activity modification, shoe modifications, braces, oral analgesics, oral nonsteroidal antiinflammatory medications, oral dietary supplements, and intraarticular injections. Furthermore, orthopaedists should be prepared to incorporate new nonoperative treatments for patients with osteoarthritis into their practice.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Matrices for cartilage repair.

Techniques for repairing focal articular cartilage defects are evolving from methods that induce a local stimulation of fibrocartilaginous repair to methods that will lead to a hyaline articular cartilage repair. Mosaicplasty and autologous chondrocyte implantation are examples of the latter. A tissue engineered hyaline cartilage implant that could be used off the self would minimize the morbidity of these techniques. However, there are significant questions that still need to be resolved before such tissue-engineered implants will be practical. Principally among these is the question of what is the ideal matrix for such an implant, particularly from the standpoint of the best material and architecture. Second, what is the ideal cell source to use with these implants. A third major unknown is what is the most ideal way to use growth factors to enhance the repair. As these issues are resolved, the prospects of a tissue engineered cartilage replacement will advance from theory to practice.

Biocompatible Materials↗
PubMed2000

Cartilage repair with autogenic perichondrium cell/polylactic acid grafts: a two-year study in rabbits.

The repair of articular cartilage injuries remains a challenge. In this 2-year study, osteochondral defects in the femoral condyles of five rabbits were repaired with an autogenic perichondrium cell/polylactic acid graft and compared with a contralateral control in which the defect remained empty. The rabbits in the group with the grafts had a higher percentage of biologically acceptable repairs (100%) than did those in the control group (80%). According to the histologic and histomorphometric analyses, the grafts augmented the intrinsic healing. Nonetheless, the results for the grafts were tarnished by a depressed repair surface and a histologic appearance not equivalent to that of normal cartilage. The application of growth factors to this model may yield a clinical treatment.

Animals↗
PubMed2000

Cartilage repair with autogenic perichondrium cell and polylactic acid grafts.

The repair of articular cartilage injuries remains a challenge, with many of the current therapeutic strategies based on the grafting or recruitment of chondrogenic tissues or cells. This 1-year study compared the repair of a 3.7-mm diameter by 3-mm deep osteochondral defect in the medial femoral condyle of 24 New Zealand White rabbits; the defect was obtained using an autogenic perichondrium cell polylactic acid composite graft with a contralateral control in which the osteochondral defect remained empty. To elucidate the effect of host immune responses on the repair process after perichondrium cell transplantation, the results of the autogenic perichondrium cell polylactic acid graft group were compared with those obtained in the authors' previous 1-year study of allogenic perichondrium cell polylactic acid composite grafts implanted in a similar model. One year after surgery, the repair site underwent gross inspection and histologic, histomorphometric, biochemical, and biomechanical analyses. The autogenic perichondrium cell polylactic acid graft group (92%) and the control group in which the osteochondral defect remained empty (88%) resulted in a high percentage of grossly acceptable repairs. The autogenic grafts appeared to augment the intrinsic healing capacity of the animals (as compared with the animals in the No Implant Group). The autogenic perichondrium cell polylactic and grafts improved the histologic appearance and percentage of Type II collagen of the cartilaginous repair tissue. Compared with allogenic grafts, the autogenic grafts had better reconstitution of the subchondral bone. However, the results of this experimental model suggest a suboptimal concentration of glycosaminoglycans in the neocartilage matrix, a depressed surface of the repair tissue, a histologic appearance that was not equivalent to that of normal articular cartilage, and reduced biomechanical properties for the repair tissue. The future application of growth factors to this model may yield a treatment that can be applied in the clinical arena.

Animals↗
PubMed1999

Nitric oxide production and apoptosis in cells of the meniscus during experimental osteoarthritis.

OBJECTIVE: To examine the pathologic changes in meniscus tissue during experimental osteoarthritis (OA) and to determine the relationship between nitric oxide (NO) synthesis, apoptosis, and meniscus degradation. METHODS: OA was induced in rabbits by anterior cruciate ligament (ACL) transection. Knees were harvested after 9 weeks and assessed for OA severity. Menisci were subjected to histologic, immunohistochemical, and electron microscopic analyses for the presence of nitrotyrosine and apoptosis. Menisci were also cultured for analysis of NO production. RESULTS: All menisci from joints with ACL transection demonstrated degenerative changes. A high number of apoptotic cells was present in the medial part of menisci, which contains chondrocytic cells. Menisci from nonoperated contralateral knees contained only small numbers of cells in apoptosis. Conditioned media from meniscus cultures contained similarly elevated levels of nitrite as cartilage cultures from the same arthritic knees. Nitrotyrosine immunoreactivity, an indicator of in vivo NO production, was prominent in menisci from knees with ACL transection. In addition, menisci from normal knees produced high levels of NO in response to in vitro stimulation with interleukin-1beta or lipopolysaccharide. CONCLUSION: These observations suggest that pathologic changes in menisci are a regular feature of experimentally induced OA and are associated with NO production and meniscus cell apoptosis.

Animals↗
PubMed1998

Chondrocyte apoptosis and nitric oxide production during experimentally induced osteoarthritis.

OBJECTIVE: Chondrocytes produce nitric oxide (NO) and undergo apoptosis in response to exogenous NO. This study sought to examine the relationship between NO synthesis, chondrocyte apoptosis, and the development of cartilage degradation during experimental osteoarthritis (OA). METHODS: OA was induced in rabbits by anterior cruciate ligament transection (ACLT). Knees were harvested after 4 weeks and assessed for OA severity and chondrocyte apoptosis. Conditioned media from cultured cartilage explants were analyzed for nitrite content. Cartilage sections were analyzed by immunohistochemistry for the presence of nitrotyrosine. RESULTS: All ACLT knees demonstrated osteoarthritic changes. Conditioned media from ACLT cartilage organ cultures contained higher levels of nitrite as compared with cartilage samples from the nonoperated side or from rabbits that had not received ACLT. Cultures of specific areas of cartilage from ACLT knees showed high levels of NO production in the medial femoral and medial tibial cartilage. Approximately 28.7% of chondrocytes isolated from ACLT cartilage and 6.7% of chondrocytes from cartilage of the nonoperated side underwent apoptosis. In situ staining demonstrated apoptotic cells in the superficial and middle zones of ACLT cartilage. A high number of apoptotic cells was present at the pannus-cartilage junction. In control cartilage, the superficial zone contained a small number of cells in apoptosis. The prevalence of apoptotic cells was significantly correlated with the levels of nitrite production and OA grade. CONCLUSION: These observations suggest that, during the early phases of OA, NO production may lead to chondrocyte apoptosis, and that both events contribute to the pathogenesis of cartilage degradation. Inhibitors of NO synthesis and chondrocyte apoptosis may therefore be of therapeutic value after cartilage injury and in patients with OA.

Animals↗
PubMed1998

Long-term effects of hyaluronan on experimental osteoarthritis in the rabbit knee.

OBJECTIVE: Long-term assessment of the effect of hyaluronan (HA) on the articular cartilage and synovium in an animal knee joint during the development of osteoarthritis (OA). DESIGN: Sixty mature New Zealand white rabbits underwent unilateral anterior cruciate ligament transection (ACLT) and were divided into two groups. Group 1 (SA) received intra-articular injections of 0.3 ml hyaluronan (HA) (i.e., ARTZ, MW: 8 x 10(5)) beginning 4 weeks after ACLT, once a week for 5 weeks. Group 2 (SV) received injections of the vehicle (phosphate buffered saline) in the same fashion as with the SA group. The contralateral nonoperated knee served as control. All animals were killed 21 weeks after surgery and their knee joints evaluated by gross morphologic, histologic, histomorphometric and biochemical analyses. RESULTS: Gross morphological inspection indicated that the femoral condyles from the knees injected with vehicle suffered more severe cartilage damage than cartilage from the knees injected with HA. Furthermore, two out of three histomorphometric parameters measured in the HA-treated cartilage (i.e., cartilage thickness and cartilage area which were not statistically different than control) provided evidence showing a protective effect of HA on the femoral condyles following ACLT. Biochemical analysis showed articular cartilage remaining on the femoral condyles following ACLT to have similar characteristics to contralateral controls. However, DNA concentration in the synovium from the ACLT knees of the vehicle-treated animals was greater than contralateral control, while this parameter was not statistically different than contralateral control in the HA treated animals. CONCLUSIONS: These results demonstrate a protective effect of HA on preservation of the articulating surface of the femoral condyle following ACLT up to 21 weeks post-surgery.

Animals↗
PubMed1998

Differences in the repair process of longitudinal and transverse injuries of cartilage in the rat knee.

OBJECTIVE: To clarify the relationship between type or direction of cartilage injury and its repair process, we investigated defects produced in rat knees histologically, immunohistochemically, and histomorphometrically. METHODS: A full-thickness cartilage injury (1 mm wide and 5 mm long) was produced on the patellar groove of one knee (L-injury) and transversely on the other knee (T-injury) in 42 male Wistar rats. Six rats each were sacrificed at 1, 2, 3, 4, 6 and 8 weeks after surgery, and cartilage tissues were obtained, prepared into 4 microns-thick histologic specimens, and stained with hematoxylin and eosin. Cartilage thickness, cartilage area, and surface roughness were measured using a computer system. Localization of S-100 proteins was evaluated with immunohistochemistry. RESULTS: Grossly, there were no difference in repair process between L- and T-injuries. However, histological and histomorphometric differences became apparent after the third week: cartilage thickness, repair area, and surface roughness showed better recovery in L-injury than in T-injury. Appearance of S-100-positive protein preceded the appearance of chondrocytes, and L-injury presented S-100 in the entire defect while S-100 in T-injury appeared mainly on the margins of the defect. CONCLUSIONS: Repair mechanisms of cartilage injury differs according to injury direction. Better repair can be obtained in the injury which is parallel to the direction of joint motion.

Animals↗
PubMed1998

Histomorphometric and biochemical effect of various hyaluronans on early osteoarthritis.

OBJECTIVE: To evaluate, histomorphometrically and biochemically, different protective effects of clinically used hyaluronans (HA). METHODS: An experimental osteoarthritis (OA) model was applied to 132 mature NZW rabbits by resecting the unilateral anterior cruciate ligament (ACL). The other knee, where ACL remained intact, served as the control. We used native HA with different molecular weights, HA-50 (MW 5-7.3 x 10(5)), HA-80 (MW 8 x 10(5)), HA-360 (MW 3.6 x 10(6)), and crosslinked HA (HA-CL). HA were injected into the joint once a week for 5 weeks (HA-50, HA-80, HA-360) or 3 weeks (HA-CL) beginning 4 weeks after ACL transection. Histomorphometric and biochemical assessment was performed 9 weeks post-transection for both the HA treated and nontreated groups. RESULTS: In gross morphological observation, cartilage degeneration was suppressed in HA treated groups, and this effect was superior in the groups receiving either HA-80 or HA-CL. Histomorphometric and biochemical analyses of the articular cartilage revealed similar results: the HA-80 and HA-CL groups showed no significant differences between the ACL transection and the control knees by histomorphometric variables, while the nontreated groups revealed significant degeneration. These evaluations were done in unblinded fashion. Biochemical analyses, including DNA synthesis in the synovium, also showed that articular cartilage and synovium in the HA-80 and HA-CL groups did not present significant changes compared to controls. CONCLUSION: In quantitative evaluation of this short term study using the OA model, native HA-80 and HA-CL presented a superior cartilage protective effect compared to the other native HA.

Animals↗
PubMed1997

Physical properties of rabbit articular cartilage after transection of the anterior cruciate ligament.

The effect of unilateral transection of the anterior cruciate ligament on the confined compression and swelling properties of the distal femoral articular cartilage of skeletally mature rabbits at 9 weeks after surgery was determined. Gross morphological grading of the transected and contralateral control distal femora stained with India ink confirmed that cartilage degeneration had been induced by ligament transection. Osteochondral cores, 1.8 mm in diameter, were harvested from the medial femoral condyles. The modulus, permeability, and electrokinetic (streaming potential) coefficient of the articular cartilage of the osteochondral cores were assessed by confined compression creep experiments. The properties (mean +/- SD) of control cartilage were: confined compression modulus, 0.75 +/- 0.28 MPa; hydraulic permeability, 0.63 +/- 0.28 x 10(-15) m2/Pa*sec; and electrokinetic coefficient, 0.16 +/- 0.31 x 10(-9) V/Pa. In transected knees, the modulus was reduced by 18% (p = 0.04), while the permeability and electrokinetic coefficient were not detectably altered. The change in modulus was accompanied by a trend (p = 0.07) toward a decrease (-11%) in the glycosaminoglycan density within the tissue, a significant increase (p < 0.001) in the water content of the cartilage after equilibration in 1 x phosphate buffered saline from 70.3 +/- 4.1% in control knees to 75.2 +/- 4.0% in transected knees, and little further swelling after tissue equilibration in hypotonic saline. The compressive modulus of the cartilage from both control and transected knees was positively correlated with the density of tissue glycosaminoglycan. The alterations in the physical properties of the articular cartilage after transection of the anterior cruciate ligament in the rabbit show trends similar to those observed in human and other animal models of osteoarthritis and provide further support for the use of this model in the study of cartilage degeneration.

Animals↗
PubMed1997

Method of histomorphometric assessment of glycosaminoglycans in articular cartilage.

A method of image analysis has been developed for use in the semiquantitative histomorphometric assessment of glycosaminoglycans in articular cartilage stained with safranin O. The reliability of the methodology is reported along with its application to the assessment of articular cartilage in a model of osteoarthritis, i.e., transection of the anterior cruciate ligament in rabbits. With this system, specimens of normal and osteoarthritic articular cartilage were assessed histomorphometrically for the following parameters: total cartilage area, percentage of safranin O stained area, mean gray scale (average stain intensity), and gray scale index (the relative total amount of glycosaminoglycans). Reproducibility was established for 12 specimens of normal cartilage and found to have a SD of less than 8% of the mean for each parameter that was measured. Image analysis of osteoarthritic cartilage revealed each of the parameters, except for average stain intensity, to be significantly lower than that in control cartilage.

Animals↗
PubMed1997

Chondrogenic phenotype of perichondrium-derived chondroprogenitor cells is influenced by transforming growth factor-beta 1.

Our laboratory has developed a method for the repair of osteochondral defects by implanting cultured perichondrial cells attached to a biodegradable polylactic acid scaffold. The success of this approach depends in part on the proliferative characteristics and the phenotype of the implanted cells. Transforming growth factor-beta 1 has been reported to influence these parameters in several mesenchymal-derived tissues in vitro and in vivo. The chondrocytic phenotype is marked by an enhanced expression of the collagen type-II gene. In this study, cultures grown from explants of rabbit rib perichondrium were exposed to exogenously added transforming growth factor-beta 1 at concentrations of 0.1-10 ng/ml of media. Cell proliferation and collagen gene expression were measured. The expression of types I and II collagen genes was analyzed by Northern blot and reverse transcriptase-polymerase chain reaction. The exogenous addition of transforming growth factor-beta 1 at a concentration of 0.1-10 ng/ml resulted in tritiated thymidine uptake by perichondrial cells, with optimum proliferative effects at 0.1 ng/ml. Transforming growth factor-beta 1 added at concentrations of 0.1 and 0.5 ng/ml significantly upregulated the expression of type-II collagen mRNAs. The results suggest that, when the chondrocytic phenotype is defined by markedly enhanced type-II collagen gene expression, the chondrocytic phenotype of explant cultures of perichondrium-derived cells is enhanced by the exogenous addition of transforming growth factor-beta 1.

Animals↗
PubMed1997

Anatomic variation of structural properties of periacetabular bone as a function of age. A quantitative computed tomography study.

The shape of the acetabulum, the volume of the periacetabular bone, and its density for 125 patients with a wide age range have been quantified using quantitative computed tomography. The goals were to study the relationship between geometric and densitometric properties and provide normative data for finite-element analysis. Significant correlations were found between acetabular diameter and (1) depth, (2) cancellous periacetabular bone density, and (3) periacetabular total bone volume. Only changes in densitometric properties significantly correlated with age. Sphericity of the acetabulum did not increase with age. Variability in bone morphology and density was found for both male and female groups. Surgeons using purely geometric measures to quantify the integrity of acetabular bone should be aware of their limitations when selecting hardware for total hip arthroplasty.

Acetabulum↗
PubMed1997

The effects of hyaluronan during the development of osteoarthritis.

Ninety-nine mature New Zealand White (NZW) rabbits underwent unilateral anterior cruciate ligament transection (ACLT) and were divided into three groups. The contralateral non-operated knees served as controls. The first group (SA) received intra-articular injections of 0.3 ml hyaluronan (HA: MW; 8 x 10(5)) beginning 4 weeks after ACLT, once a week for 5 weeks. The second group (SV) was injected with vehicle (carrier of HA) in the same fashion as the SA group. The third group (SN) served as a nontreatment group post ACLT. All animals were killed 9 weeks post-surgery and were assessed by gross morphology, histomorphometry and biochemical analysis. Gross morphologic changes on the femoral cartilage in the SA group were less severe than those in the SV and SN groups. Cartilage thickness, cartilage area, and thickness of synovial lining cell layer histomorphometric parameters were measured, showing a positive effect of HA on the preservation of articular cartilage and synovial tissue. Similarly, the cartilage and synovial tissues from knees injected with HA did not demonstrate significant alterations from contralateral controls as measured by biochemical analysis [i.e., water content, pyridinoline concentration, glycosaminoglycan (GAG) content for the cartilage, and DNA concentration for the synovial tissue].

Animals↗