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Biomedical subjects

J J Rodrigo

Publications and source records attributed to J J Rodrigo.

At least 19 recordsLinked to original sources

Microfracture and bone morphogenetic protein 7 (BMP-7) synergistically stimulate articular cartilage repair.

OBJECTIVE: Microfracture is used to treat articular cartilage injuries, but leads to the formation of fibrocartilage rather than native hyaline articular cartilage. Since bone morphogenetic protein 7 (BMP-7) induces cartilage differentiation, we hypothesized that the addition of the morphogen would improve the repair tissue generated by microfracture. We determined the effects of these two treatments alone and in combination on the quality and quantity of repair tissue formed in a model of full-thickness articular cartilage injury in adolescent rabbits. DESIGN: Full-thickness defects were made in the articular cartilage of the patellar grooves of forty, 15-week-old rabbits. Eight animals were then assigned to (1) no further treatment (control), (2) microfracture, (3) BMP-7, (4) microfracture with BMP-7 in a collagen sponge (combination treatment), and (5) microfracture with a collagen sponge. Animals were sacrificed after 24 weeks at 39 weeks of age. The extent of healing was quantitated by determining the thickness and the surface area of the repair tissue. The quality of the repair tissue was determined by grading specimens using the International Cartilage Repair Society Visual Histological Assessment Scale. RESULTS: Compared to controls, BMP-7 alone increased the amount of repair tissue without affecting the quality of repair tissue. Microfracture improved both the quantity and surface smoothness of repair tissue. Compared to either single treatment, the combination of microfracture and BMP-7 increased both the quality and quantity of repair tissue. CONCLUSIONS: Microfracture and BMP-7 act synergistically to stimulate cartilage repair, leading to larger amounts of repair tissue that more closely resembles native hyaline articular cartilage.

Animals↗

A mechanistic model for internal bone remodeling exhibits different dynamic responses in disuse and overload.

Bone is a dynamic tissue which, through the process of bone remodeling in the mature skeleton, renews itself during normal function and adapts to mechanical loads. It is, therefore, important to understand the effect of remodeling on the mechanical function of bone, as well as the effect of the inherent time lag in the remodeling process. In this study, we develop a constitutive model for bone remodeling which includes a number of relevant mechanical and biological processes and use this model to address differences in the remodeling behavior as a volume element of bone is placed in disuse or overload. The remodeling parameters exhibited damped oscillatory behavior as the element was placed in disuse, with the amplitude of the oscillations increasing as the severity of disuse increased. In overload situations, the remodeling parameters exhibited critically sensitive behavior for loads beyond a threshold value. These results bear some correspondence to experimental findings, suggesting that the model may be useful when examining the importance of transient responses for bone in disuse, and for investigating the role fatigue damage removal plays in preventing or causing stress fractures. In addition, the constitutive algorithm is currently being employed in finite element simulations of bone adaptation to predict important features of the internal structure of the normal femur, as well as to study bone diseases and their treatment.

Animals↗

Microfracture: surgical technique and rehabilitation to treat chondral defects.

Full-thickness articular cartilage defects rarely heal spontaneously. Some patients may not have clinically significant problems from chondral defects, but most eventually have degenerative changes. Techniques to treat chondral defects include abrasion, drilling, autografts, allografts, and cell transplantation. The senior author (JRS) developed the microfracture technique to enhance chondral resurfacing by providing a suitable environment for new tissue formation and taking advantage of the body's own healing potential. Microfracture has been done in more than 1800 patients. Specially designed awls are used to make multiple perforations, or microfractures, into the subchondral bone plate. Perforations are made as close together as possible, but not so close that one breaks into another. They usually are approximately 3 to 4 mm apart. The integrity of the subchondral bone plate must be maintained. The released marrow elements (including mesenchymal stem cells, growth factors, and other healing proteins) form a surgically induced super clot that provides an enriched environment for new tissue formation. The rehabilitation program is crucial to optimize the results of the surgery. It promotes the ideal physical environment for the marrow mesenchymal stem cells to differentiate into articular cartilagelike cells, ultimately leading to development of a durable repair cartilage that fills the original defect.

Cartilage, Articular↗

Total knee replacement with interlocking stems: a preliminary report.

Revision total knee replacements or primary total knee replacements with large amounts of bone loss frequently require long-stemmed prostheses to stabilize the components. The hypothesis of the current study was that long-stemmed prostheses can be fixed with interlocking screws, provide a successful outcome, avoid extensive stress-shielding, and allow easy revision in the future. Ten patients with a minimum 2-year followup were studied. Outcomes were studied preoperatively and postoperatively using the Short Form-12 questionnaires, physical examinations, and radiographs. Complications were recorded. Ability to do activities of daily living, strenuous work, and sedentary work were recorded on a 10-point analog scale. Results indicated that 80% of stems well-fixed as shown on serial radiographs, functional outcome scores postoperatively improved significantly from preoperatively, pain was improved significantly, and positive bone remodeling without stress-shielding was seen in 80% of patients, but 20% had significant stress-shielding in the metaphysis. Complications included two periprosthetic fractures for which the patients did not require revision surgery, and one infection. Long-stemmed total knee components with interlocking fixation seem to be a reasonable alternative when large bone defects exist in the femur or tibia.

Adult↗

[The microfracture technic in the management of complete cartilage defects in the knee joint].

Full thickness defects of the articular cartilage rarely heal spontaneously. While some patients do not develop clinically significant problems from chondral defects, most eventually develop degenerative changes associated with the cartilage damage over time. Techniques to treat chondral defects include abrasion, drilling, tissue autografts, allografts, and cell transplantation. The senior author has developed a procedure referred to as the "microfracture." This technique enhances chondral resurfacing by providing a suitable environment for tissue regeneration and by taking advantage of the body's own healing potential. This technique has now been used in more than 1400 patients. Specially designed awls are used to make multiple perforations, or "microfractures", into the subchondral bone plate. The perforations are made as close together as necessary, but not so close that one breaks into another. Consequently, the microfracture holes are approximately three to four millimeters apart (or 3 to 4 holes per square centimeter). Importantly, the integrity of the subchondral bone plate is maintained. The released marrow elements form a "super clot" which provides an enriched environment for tissue regeneration. Follow up with long term results of more than 8 years have been positive and very encouraging.

Bone Regeneration↗

Adenosine 5'-triphosphate, uridine 5'-triphosphate, bradykinin, and lysophosphatidic acid induce different patterns of calcium responses by human articular chondrocytes.

Small calcium-mobilizing inflammatory mediators have been implicated in joint pathology. Here we demonstrate that bradykinin, adenosine 5'-triphosphate, uridine 5'-triphosphate, and lysophosphatidic acid raise the intracellular calcium concentration ([Ca2+]i) in human articular chondrocytes. Heterologous cross-desensitization experiments showed that the uridine 5'-triphosphate response was abolished by prior treatment with adenosine 5'-triphosphate and, conversely, that the adenosine 5'-triphosphate response was abolished by prior treatment with uridine 5'-triphosphate; this indicated competition for the same receptor site, whereas bradykinin and lysophosphatidic acid did not compete with other ligands. Pretreatment with thapsigargin abolished ligand-mediated Ca2+ responses but not vice versa; this confirmed that Ca2+ release occurred from intracellular stores. Single-cell analysis of Fura-2 acetoxymethyl ester loaded chondrocytes showed mediator-dependent patterns of oscillatory Ca2+ changes in a subset of cells when challenged with submaximal concentrations of bradykinin, adenosine 5'-triphosphate, or uridine 5'-triphosphate in the presence of extracellular Ca2+. However, no oscillatory responses were seen after a challenge with lysophosphatidic acid. Therefore, although a number of different Ca2+-mobilizing ligands activate chondrocytes, the differences that occur in the temporal patterning of Ca2+ responses may result in unique mediator-dependent changes in cellular activity.

Adenosine Triphosphate↗

Treatment of articular cartilage defects in athletes: an analysis of functional outcome and lesion appearance.

This article characterizes chondral injuries and reviews the results of microfracture treatment in high-level competitive and recreational athletes. Thirty-eight high-level and 140 recreational athletes completed functional questionnaires preoperatively and yearly postoperatively, recording symptoms, function, and activity level. Second-look arthroscopy tapes were available in 26 high-level and 54 recreational athletes. The mean follow-up for the high-level athletes was 3.7 +/- 1.4 years. Chondral defects averaged 223 +/- 180 mm2. Lesion size and follow-up were not significantly different in the recreational group. Functional questionnaire responses demonstrated significant improvements from the time of microfracture to final follow-up. Improvement in function and symptoms was similar for the competitive and recreational athletes.

Adolescent↗

Immune response to nonspecific and altered tissue antigens in soft tissue allografts.

Soft tissue allografts have many uses in orthopaedic surgery, including knee ligament reconstruction, hand tendon surgery, shoulder instability, and rotator cuff reconstruction. The predictable biologic incorporation of soft tissue allografts without rejection or fear of disease transmission continues to be a goal of basic science researchers. A review of the current knowledge if the immune system response to donor specific, nonspecific, and altered tissue antigens in soft tissue or tendon allografts is presented. An in vitro study was done in an attempt to decrease immunogenicity of a frozen bone-ligament graft by adding irrigation with Betadine scrub solution and hydrogen peroxide to the conventional storage process of freezing. Although the irrigation with cytotoxic agents would undoubtedly further decrease immunogenicity, it also decreased stiffness and maximum load by 15%. Whether this decreased strength and stiffness would compromise the incorporation and long term success of soft tissue allografts would need to be studied by in vitro experiments.

Anti-Infective Agents, Local↗

Immune response inhibition by irrigating subchondral bone with cytotoxic agents.

Attempts have been made (in the recent past) to inhibit the immune response to fresh osteoarticular (shell) allografts because the occurrence and the magnitude of this response is considerably greater and more harmful than that seen after frozen bone and soft tissue allografts. To decrease in immunogenicity of these fresh grafts, the subchondral bone of rat distal femur allografts was irrigated with Betadine scrub solution (n = 10) or Triton-X (n = 11) before transplantation (Study 1). The Triton-X significantly reduced the immunogenicity of the grafts, but the Betadine scrub solution had no effect. A similar experiment with Triton-X was done in sheep where trochlear knee autografts (n = 3) were compared with unirrigated allografts (n = 3) and allografts receiving irrigation with Triton-X (n = 3) (Study 2). All 3 Triton-X irrigated allografts had no immune response, and showed much improved grafts compared with the control allografts (where an immune response developed in 2 of 3). Neither of the 2 allograft groups were as good as the autografts. These techniques may prove useful for inhibiting the recipient immune responses to fresh osteoarticular allografts in humans requiring partial joint reconstruction.

Animals↗

Immune response to synthetic materials. Sensitization of patients receiving orthopaedic implants.

Metallic orthopaedic devices are composed of elements that are known to be skin sensitizers in the general population. There is concern about the possibility of sensitivity reactions in patients bearing these implants. Blood samples were drawn from 22 patients having primary total joint replacement and who had no known prior metal allergies or exposure. Repeat blood samples were drawn 3 months to 1 year later. All preoperative blood samples showed no immune reactions against titanium, cobalt, chromium, or nickel ion solutions in a leukocyte migration inhibition test. Thirty two percent (7 of 22) of the patients developed sensitivity to at least 1 of the antigens, but only 5 percent (1 of 22) developed a severe reaction. Review of the literature and these studies has indicated that such reactions can occur. However, the incidence seems to be very low.

Foreign-Body Reaction↗

Effects of human knee synovial fluid on chondrogenesis in vitro.

To evaluate the healing environment of chondral defects, synovial fluid samples from knees of 25 patients with a traumatic chondral defect were evaluated. Effect of the synovial fluid on chondrogenesis was measured using a chick limb bud bioassay. Samples from 11 of 17 acutely injured knees stimulated chondrogenesis, samples from 4 were inhibitory, and samples from 2 showed no effect. Samples from six of eight chronically injured knees inhibited chondrogenesis; the other two samples stimulated chondrogenesis. The relationship between acute versus chronic injury and effect of synovial fluid on chondrogenesis was statistically significant. We conclude that synovial fluid contains factors that stimulate cartilage healing in the acute period following traumatic injury, but this effect can become inhibitory if the lesion is allowed to become chronic.

Adult↗

Anterior cruciate ligament allograft transplantation in dogs.

The biomechanical and clinical performance of bone-ligament-bone anterior cruciate ligament (ACL) allografts was studied in eight dogs. Allografts were collected from skeletally mature, healthy dogs using aseptic technique, and stored at -70 degrees for three to five weeks before implantation. The allografts were size-matched to the recipient dogs using ACL length and then rigidly fixed in position with interference screws and Kirschner wires. Three dogs regained a normal gait, and their grafts sustained breaking loads that were 25%, 41%, and 59% of controls. Partial or complete graft failure occurred in the other five dogs at some point in the study. Four had intraligamentous rupture and one had an avulsion fracture of the femoral attachment site. Joint-fluid cytology was normal in all eight dogs. Histologic examination showed persistent lymphoplasmacytic infiltrate. Eventually the allograft cores were incorporated in the host bed. Hyperplasia and fibrosis of the synovial membrane were diffuse and persisted as focal accumulations of mononuclear inflammatory cells.

Animals↗

Tissue banking.

The Scientific Board of the California Medical Association presents the following inventory of items of progress in orthopedics. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, or scholars to stay abreast of these items of progress in orthopedics that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another. The items of progress listed below were selected by the Advisory Panel to the Section on Orthopedics of the California Medical Association, and the summaries were prepared under its direction.

Humans↗

Interlocking femoral components for revision arthroplasty with allografts.

The use of interlocking screws has been advocated to fix major proximal femoral allografts to femoral prostheses. This study examines the effect of interlocking screws on strength of the component. Model femoral components were tested in axial compression. Drilling one hole diagonally (lateral to medial), drilling one hole anterior to posterior, or drilling one diagonal hole plus one anterior-to-posterior hole did not significantly decrease failure load compared to controls with no holes. However, two diagonal holes or horizontal, medial-to-lateral holes were weaker. Four cases have been done with proximal femoral allografts fixed to porous-coated femoral components with proximal and distal interlocking screws. Initial results in these cases are good.

Adult↗

Replacement of the anterior cruciate ligament. A comparison of autografts and allografts in dogs.

To compare the efficacy of allograft versus autograft replacement of the anterior cruciate ligament, 15 dogs had the ligament cut and replaced 1 month later: 11 dogs received a frozen bone-ligament-bone allograft cruciate ligament, while 4 dogs received a standard autogenous replacement with iliotibial band. Three of 11 allograft dogs developed postoperative infections and were removed from the study; and two of the remaining eight allograft ligaments were absent at autopsy. All the autograft ligaments were present. From serial clinical and radiographic examinations, there were no differences observed in the two groups. Autopsy studies at 4 months, however, showed an increased inflammatory, pannus-like reaction about the origins and insertions of the six allograft ligaments as compared with the four autografts. The ligament hydroxyproline uptake was lower in the allograft group, averaging 60 percent of the contralateral unoperated on control versus equal to the control in the autograft group. The tensile strength of the allografts reached only 17 percent of the control value versus 41 percent for the autografts. Lymphocytotoxicity testing at 1 month revealed a donor-specific antibody response in 4 of 8 allograft dogs; however, no histologic evidence of immune response was observed in the ligaments. The synovial fluid leukocyte count was elevated in the allograft group at 4 months. The increased synovial leukocyte counts and joint cartilage erosion, the decreased strength and metabolic activity of the grafts, and the evidence of an immune response in the allograft dogs do not support implantation of cadaver cruciate ligaments clinically at this time.

Animals↗

Inhibition of the immune response to experimental fresh osteoarticular allografts.

The immune response to osteoarticular allografts is capable of destroying the cartilage--a tissue that has antigens on its cells identical to those on the bone and marrow cells. Osteoarticular allografts of the distal femur were performed in rats using various methods to attempt to temporarily inhibit the antibody response. The temporary systemic immunosuppressant regimens investigated were cyclophosphamide, azathioprine and prednisolone, cyclosporine A, and total lymphoid irradiation. The most successful appeared to be cyclosporine A, but significant side effects were observed. To specifically inhibit the immune response in the allograft antigens without systemically inhibiting the entire immune system, passive enhancement and preadministration of donor blood were tried. Neither was as effective as coating the donor bone with biodegradable cements, a method previously found to be successful. Cyclosporine A was investigated in dogs in a preliminary study of medial compartmental knee allografts and was found to be successful in inhibiting the antibody response and in producing a more successful graft; however, some significant side effects were similarly observed.

Animals↗

An in vitro study of the structural properties of deep-frozen versus freeze-dried, ethylene oxide-sterilized canine anterior cruciate ligament bone-ligament-bone preparations.

The effect of two preparation and storage methods on the structural properties of canine anterior cruciate ligament (ACL) bone-ligament-bone preparations was determined. In Group 1, one knee joint from each dog was tested after storage at -70 degrees for eight to 12 weeks. In Group 2, one knee joint from each dog was sterilized using ethylene oxide, freeze-dried, and then stored at room temperature for four to five weeks prior to mechanical testing. In both groups, the contralateral joint was tested fresh and used as a control. The bone-ligament-bone preparations were loaded in tension until failure and the load at failure, stiffness, and maximum elongation were measured. No preparation method caused a significant decline in breaking strength. In both groups, however, there was a significant increase in elongation at failure noted in the test specimens. This was accompanied, in Group 1 (deep-frozen), by a significant decrease in stiffness in the test joints. A similar trend toward decreased stiffness was observed in the test joints from Group 2 (freeze-dried).

Animals↗