Altered regional loading patterns on articular cartilage following meniscectomy are not fully restored by autograft meniscal transplantation.

OBJECTIVE: To quantify the changes in regional dynamic loading patterns on tibial articular cartilage during simulated walking following medial meniscectomy and meniscal transplantation. METHODS: Seven fresh frozen human cadaveric knees were tested under multidirectional loads mimicking the activity of walking, while the contact stresses on the tibial plateau were synchronously recorded using an electronic sensor. Each knee was tested for three conditions: intact meniscus, medial meniscectomy, and meniscal transplantation. The loading profiles at different locations were assessed and common loading patterns were identified at different sites of the tibial plateau using an established numerical algorithm. RESULTS: Three regional patterns were found on the tibial plateau of intact knees. Following medial meniscectomy, the area of the first pattern which was located at the posterior aspect of the medial plateau was significantly reduced, while the magnitude of peak load was significantly increased by 120%. The second pattern which was located at the central-posterior aspects of the lateral plateau shifted anteriorly and laterally without changing its magnitude. The third pattern in the cartilage-to-cartilage contact region of the medial plateau was absent following meniscectomy. Meniscal transplantation largely restored the first pattern, but it did not restore the other two patterns. CONCLUSION: There are site-dependent changes in regional loading patterns on both the medial and lateral tibial plateau following medial meniscectomy. Even when a meniscal autograft is used where the geometry and material properties are kept constant, the only region in which the loading pattern is restored is at posterior aspect of the medial plateau.

Correlation of meniscal T2* with multiphoton microscopy, and change of articular cartilage T2 in an ovine model of meniscal repair.

OBJECTIVE: To correlate meniscal T2* relaxation times using ultra-short echo time (UTE) magnetic resonance imaging (MRI) with quantitative microscopic methods, and to determine the effect of meniscal repair on post-operative cartilage T2 values. DESIGN: A medial meniscal tear was created and repaired in the anterior horn of one limb of 28 crossbred mature ewes. MR scans for morphological evaluation, meniscal T2* values, and cartilage T2 values were acquired at 0, 4 and 8 months post-operatively for the Tear and Non-Op limb. Samples of menisci from both limbs were analyzed using multiphoton microscopy (MPM) analysis and biomechanical testing. RESULTS: Significantly prolonged meniscal T2* values were found in repaired limbs than in control limbs, P < 0.0001. No regional differences of T2* were detected for either the repaired or control limbs in the anterior horn. Repaired limbs had prolonged cartilage T2 values, primarily anteriorly, and tended to have lower biomechanical force to failure at 8 months than Non-Op limbs. MPM autofluorescence and second harmonic generation data correlated with T2* values at 8 months (ρ = -0.48, P = 0.06). CONCLUSIONS: T2* mapping is sensitive to detecting temporal and zonal differences of meniscal structure and composition. Meniscal MPM and cartilage T2 values indicate changes in tissue integrity in the presence of meniscal repair.

Cell therapy in orthopaedics: where are we in 2019?

Stem cells are defined by their potential for self-renewal and the ability to differentiate into numerous cell types, including cartilage and bone cells. Although basic laboratory studies demonstrate that cell therapies have strong potential for improvement in tissue healing and regeneration, there is little evidence in the scientific literature for many of the available cell formulations that are currently offered to patients. Numerous commercial entities and 'regenerative medicine centres' have aggressively marketed unproven cell therapies for a wide range of medical conditions, leading to sometimes indiscriminate use of these treatments, which has added to the confusion and unpredictable outcomes. The significant variability and heterogeneity in cell formulations between different individuals makes it difficult to draw conclusions about efficacy. The 'minimally manipulated' preparations derived from bone marrow and adipose tissue that are currently used differ substantially from cells that are processed and prepared under defined laboratory protocols. The term 'stem cells' should be reserved for laboratory-purified, culture-expanded cells. The number of cells in uncultured preparations that meet these defined criteria is estimated to be approximately one in 10 000 to 20 000 (0.005% to 0.01%) in native bone marrow and 1 in 2000 in adipose tissue. It is clear that more refined definitions of stem cells are required, as the lumping together of widely diverse progenitor cell types under the umbrella term 'mesenchymal stem cells' has created confusion among scientists, clinicians, regulators, and our patients. Validated methods need to be developed to measure and characterize the 'critical quality attributes' and biological activity of a specific cell formulation. It is certain that 'one size does not fit all' - different cell formulations, dosing schedules, and culturing parameters will likely be required based on the tissue being treated and the desired biological target. As an alternative to the use of exogenous cells, in the future we may be able to stimulate the intrinsic vascular stem cell niche that is known to exist in many tissues. The tremendous potential of cell therapy will only be realized with further basic, translational, and clinical research. Cite this article: Bone Joint J 2019;101-B:361-364.

Classification systems for platelet-rich plasma.

There is good scientific rationale to support the use of growth factors to promote musculoskeletal tissue regeneration. However, the clinical effectiveness of platelet-rich plasma (PRP) and other blood-derived products has yet to be proven. Characterization and reporting of PRP preparation protocols utilized in clinical trials for the treatment of musculoskeletal disease is highly inconsistent, and the majority of studies do not provide sufficient information to allow the protocols to be reproduced. Furthermore, the reporting of blood-derived products in orthopaedics is limited by the multiple PRP classification systems available, which makes comparison of results between studies challenging. Several attempts have been made to characterize and classify PRP; however, no consensus has been reached, and there is lack of a comprehensive and validated classification. In this annotation, we outline existing systems used to classify preparations of PRP, highlighting their advantages and limitations. There remains a need for standardized universal nomenclature to describe biological therapies, as well as a comprehensive and reproducible classification system for autologous blood-derived products. Cite this article: Bone Joint J 2019;101-B:891-896.

Immunolocalization of cytokines and their receptors in adhesive capsulitis of the shoulder.

The purpose of this study was to test the hypothesis that specific cytokines are involved in the initiation and evolution of the fibrotic process in adhesive capsulitis of the shoulder. After approval from the Institutional Review Board, biopsies of shoulder capsule and synovium were collected during shoulder arthroscopy from 19 patients with adhesive capsulitis, 14 patients with nonspecific synovitis and no fibrosis or clinical evidence of adhesive capsulitis, and seven patients undergoing surgery for another pathology who had a normal capsule and synovium. Immunohistochemical localization with monoclonal antibodies to transforming growth factor-beta and its receptor, platelet-derived growth factor and its receptor, basic fibroblast growth factor, interleukin-1 beta, tumor necrosis factor-alpha, and hepatocyte growth factor was performed using standard immunoperoxidase techniques. The frequency of cytokine staining was correlated with the clinical diagnosis. Synovial cells, fibroblasts, T-cells, and B-cells were identified with specific antibodies, and newly synthesized matrix was examined for type-I and type-III collagen by immunohistochemical staining. The predominant cell types present were synovial cells and fibroblasts. Staining for type-III collagen in adhesive capsulitis tissues indicated new deposition of collagen in the capsule. There was staining for transforming growth factor-beta and its receptor, platelet-derived growth factor and its receptor, interleukin-1 beta, and tumor necrosis factor-alpha in adhesive capsulitis and nonspecific synovitis tissues, compared with minimal staining in normal capsule. Staining was more frequent in synovial cells than in capsular cells. The frequency of cell and matrix staining for transforming growth factor-beta, platelet-derived growth factor, and hepatocyte growth factor was greater in adhesive capsulitis tissues than in those from patients with nonspecific synovitis. No difference in the frequency of staining between primary (idiopathic) and secondary adhesive capsulitis was found. The results of this study indicate that adhesive capsulitis involves both synovial hyperplasia and capsular fibrosis. Cytokines such as transforming growth factor-beta and platelet-derived growth factor may be involved in the inflammatory and fibrotic processes in adhesive capsulitis. Matrix-bound transforming growth factor-beta may act as a persistent stimulus, resulting in capsular fibrosis. Understanding the basic pathophysiology of adhesive capsulitis is an important step in the development of clinically useful antifibrotic agents that may serve as novel treatments for patients with this conditions.

Histological analysis of human meniscal allografts. A preliminary report.

BACKGROUND: Little is known about the biology of meniscal allograft transplantation in humans. In particular, little information is available about the phenotype of the cells that repopulate the allograft, whether an immune response is elicited against the graft, and whether the repopulating cells synthesize normal extracellular matrix components. METHODS: A small biopsy specimen of the meniscal allograft (twenty-eight menisci in twenty-five patients) and the adjacent synovial membrane (sixteen patients) was harvested during follow-up arthroscopy in patients who had undergone meniscal allograft transplantation at a mean of sixteen months earlier. Seventeen patients had undergone concomitant reconstruction of the anterior cruciate ligament with an allograft. Normal menisci (unimplanted allografts) and synovial specimens from age-matched controls were examined as well. All twenty-eight meniscal allografts were examined histologically. Immunohistochemical analysis was carried out on ten menisci and nine synovial specimens with use of monoclonal antibodies to class-I and class-II major histocompatibility complex antigens, CD-8, CD-11b, and CD-19 epitopes, as well as other epitopes, to demonstrate immunogenic macromolecules, cytotoxic T-lymphocytes, activated macrophages, and B-lymphocytes. RESULTS: Most of the specimens demonstrated incomplete repopulation with viable cells. The repopulating cells stained positively with phenotype markers for both synovial cells and fibroblasts. Polarized light microscopy demonstrated evidence of active remodeling of the matrix. The cells in frozen, unimplanted menisci stained positively for class-I and class-II human leukocyte antigens, indicating immunogenicity at the time of transplantation. Overall, nine of twelve specimens contained immunoreactive cells (B-lymphocytes or cytotoxic T-cells) in the meniscus or synovial tissue. However, only a small number of these cells was present. There was no evidence of frank immunological rejection. The clinical outcome (success or failure of the transplant) was not related to the overall histological score or to the presence of an immune response in the meniscal or synovial biopsy specimen. CONCLUSIONS: Human meniscal allograft transplants are repopulated with cells that appear to be derived from the synovial membrane; these cells appear to actively remodel the matrix. Although there is histological evidence of an immune response directed against the transplant, this response does not appear to affect the clinical outcome. The presence of histocompatibility antigens on the meniscal surface at the time of transplantation (even after freezing) indicates the potential for an immune response against the transplant. CLINICAL RELEVANCE: Despite the absence of frank immunological rejection, a subtle immune reaction may affect the healing, incorporation, and revascularization of the graft. It is possible that the structural remodeling associated with cellular repopulation may render the meniscus more susceptible to injury.

Tendon-healing in a bone tunnel. A biomechanical and histological study in the dog.

Our study evaluated tendon-to-bone healing in a dog model. Twenty adult mongrel dogs had a transplantation of the long digital extensor tendon into a 4.8-millimeter drill-hole in the proximal tibial metaphysis. Four dogs were killed at each of five time-periods (two, four, eight, twelve, and twenty-six weeks after the transplantation), and the histological and biomechanical characteristics of the tendon-bone interface were evaluated. Serial histological analysis revealed progressive reestablishment of collagen-fiber continuity between the bone and the tendon. A layer of cellular, fibrous tissue was noted between the tendon and the bone, along the length of the bone tunnel; this layer progressively matured and reorganized during the healing process. The collagen fibers that attached the tendon to the bone resembled Sharpey fibers. High-resolution radiographs showed remodeling of the trabecular bone that surrounded the tendon. At the two, four, and eight-week time-periods, all specimens had failed by pull-out of the tendon from the bone tunnel. The strength of the interface was noted to have significantly and progressively increased between the second and the twelfth week after the transplantation. At the twelve and twenty-six-week time-periods, all specimens had failed by pull-out of the tendon from the clamp or by mid-substance rupture of the tendon. The progressive increase in strength was correlated with the degree of bone ingrowth, mineralization, and maturation of the healing tissue, noted histologically.

Reliability, validity, and responsiveness of four knee outcome scales for athletic patients.

BACKGROUND: Many patient-based knee-rating scales are available for the evaluation of athletic patients. However, there is little information on the measurement properties of these instruments and therefore no evidence to support the use of one questionnaire rather than another. The goal of the present study was to determine the reliability, validity, and responsiveness of four knee-rating scales commonly used for the evaluation of athletic patients: the Lysholm scale, the subjective components of the Cincinnati knee-rating system, the American Academy of Orthopaedic Surgeons sports knee-rating scale, and the Activities of Daily Living scale of the Knee Outcome Survey. METHODS: All patients in the study had a disorder of the knee and were active in sports (a Tegner score of 4 points). Forty-one patients who had a knee disorder that had stabilized and who were not receiving treatment were administered all four questionnaires at baseline and again at a mean of 5.2 days (range, two to fourteen days) later to test reliability. Forty-two patients were administered the scales at baseline and at a minimum of three months after treatment to test responsiveness. The responses of 133 patients at baseline were studied to test construct validity. RESULTS: The reliability was high for all scales, with the intraclass correlation coefficient ranging from 0.88 to 0.95. As for construct validity, the correlations among the knee scales ranged from 0.70 to 0.85 and those between the knee scales and the physical component scale of the Short Form-36 (SF-36) and the patient and clinician severity ratings ranged from 0.59 to 0.77. Responsiveness, measured with the standardized response mean, ranged from 0.8 for the Cincinnati knee-rating system to 1.1 for the Activities of Daily Living scale. CONCLUSIONS: All four scales satisfied our criteria for reliability, validity, and responsiveness, and all are acceptable for use in clinical research.

Meniscal allografts--where do we stand?

Meniscal transplantation has been recommended for selected meniscus-deficient patients in an effort to forestall progressive joint degeneration. Meniscal allograft transplantation may be considered for patients with symptoms (pain and swelling) due to meniscal deficiency in an effort to prevent progressive articular cartilage degeneration. Medial meniscal transplantation may also be considered during concomitant anterior cruciate ligament reconstruction, since absence of the medial meniscus results in increased forces in the anterior cruciate ligament graft. Contraindications for meniscal transplantation include advanced articular cartilage degeneration (especially on the flexion weightbearing zone of the condyle), axial malalignment, and flattening of the femoral condyle. Patient evaluation should include standing, long-leg radiographs for assessment of the mechanical axis and magnetic resonance imaging with appropriate pulse sequences for evaluation of hyaline cartilage thickness. Fresh-frozen and cryopreserved allografts are currently the most commonly used transplantation materials. Appropriate graft sizing is critical; most tissue banks size the meniscus based on radiographic tibial plateau measurements. Early results of meniscal transplantation indicate predictable improvements in pain, swelling, and knee function; however, no long-term results are available. Poor results have been reported in patients with advanced cartilage degeneration. Objective evaluations often demonstrate some degree of degeneration of the posterior horn of the transplant. Earlier transplantation should be considered for patients with known meniscal deficiency.

Postexercise increase in nitric oxide in football players with muscle cramps.

Nitric oxide, a free radical inter- and intracellular messenger molecule, is important in exercise physiology. This study tested the hypothesis that serum nitric oxide concentrations change after strenuous exercise with severe generalized muscle cramps. The study group consisted of 77 professional football players in preseason training. All players' concentrations of serum nitrite and of other serum chemicals were determined during their preseason evaluations and compared with the concentrations in 40 serum samples taken from 25 of those same players who required intravenous rehydration for severe generalized muscle cramps after a training session. Player weight and percentage of body fat were significantly higher in players who received intravenous fluids than in players who did not. The serum of players requiring intravenous hydration showed evidence of skeletal muscle breakdown (increases in lactate dehydrogenase, creatinine phosphokinase, aspartate aminotransferase, and alanine aminotransferase) and of dehydration (elevations in protein, blood urea nitrogen, and cholesterol). The major finding, however, was a nearly 300% increase in serum nitrite concentrations in players requiring rehydration. There were no correlations between concentrations of nitrate and of any of the other serum chemicals. These data support the hypothesis that large amounts of nitric oxide are synthesized in professional football players after strenuous exercise with severe muscle cramps. The study design did not allow us to determine whether this increase in nitric oxide was due to exercise or muscle cramps or both, but it does provide a basis for evaluating these relationships.

Augmentation of tendon healing in an intraarticular bone tunnel with use of a bone growth factor.

We hypothesized that an exogenous bone growth factor could augment healing of a tendon graft in a bone tunnel in a rabbit anterior cruciate ligament-reconstruction model. Seventy rabbits underwent bilateral anterior cruciate ligament reconstructions with a semitendinosus tendon graft. One limb received a collagen sponge carrier vehicle containing a mixture of bone-derived proteins while the contralateral limb was treated with either no sponge or a sponge without bone-derived proteins. The reconstruction was evaluated at 2, 4, or 8 weeks with histologic, biomechanical, and magnetic resonance imaging analysis. Histologic analysis demonstrated that specimens treated with bone-derived proteins had a more consistent, dense interface tissue and closer apposition of new bone to the graft, with occasional formation of a fibrocartilaginous interface, when compared with control specimens. The treated specimens had significantly higher load-to-failure rates than did control specimens. Treatment with bone-derived proteins resulted in an average increase in tensile strength of 65%. The treated specimens were stronger than control specimens at each time point, but the difference was greatest at 8 weeks. On the basis of signal characteristics and new bone formation, magnetic resonance imaging was useful for predicting which limb was treated, the site of failure, and the limbs with higher load-to-failure values. This study demonstrates the potential for augmenting tendon healing in an intraarticular bone tunnel using an osteoinductive growth factor.

Analysis of collagen and elastic fibers in shoulder capsule in patients with shoulder instability.

This study examined collagen cross-links, collagen fibril diameter and density, amino acid composition, and elastic fibers in shoulder capsule and skin in four patient groups: 1) unidirectional anterior instability (N = 8); 2) multidirectional instability/primary surgery (N = 6); 3) multidirectional instability/revision surgery (N = 6); and 4) no history of instability (N = 5). Compared with normal capsule, capsule from groups 1 and 2 had more stable and reducible collagen cross-links, significantly greater mean collagen fibril diameter, more cysteine, and a higher density of elastin staining. Compared with shoulder capsule in groups 1 and 2, shoulder capsule from group 3 contained significantly more reducible cross-links, smaller-diameter collagen fibrils, decreased collagen fibril density, and an increased density of elastin staining. There were no significant differences in any parameters between groups 1 and 2. We hypothesized that repeated capsular deformation in patients with shoulder instability results in changes in the capsule that increase its strength and resistance to stretching. Skin analyses demonstrated a significantly smaller mean collagen fibril diameter in skin from group 2 compared with group 1, suggesting the possibility of an underlying connective tissue abnormality.

Use of recombinant human bone morphogenetic protein-2 to enhance tendon healing in a bone tunnel.

This study examines the hypothesis that recombinant human bone morphogenetic protein-2 can enhance bone ingrowth into a tendon graft placed into a bone tunnel. We transplanted the long digital extensor tendon into a drill hole in the proximal tibia in 65 adult mongrel dogs. We applied two different doses of the bone morphogenetic protein to the tendon-bone interface in one limb using an absorbable type I collagen sponge carrier and only the collagen sponge to the contralateral (control) limb. The healed tendon-bone attachment was evaluated at serial times between 3 days and 8 weeks using radiography, histologic examination, and biomechanical testing. At all time points, histologic and radiographic examination demonstrated more extensive bone formation around the tendon with closer apposition of new bone to the tendon in the protein-treated limb than in the paired control limb. Biomechanical testing demonstrated higher tendon pull-out strength in the protein-treated side at all time points, with a statistically significant difference between the low-dose-treated side and the control side at 2 weeks. The histologic and biomechanical data suggested superior healing at the lower protein dose. This study demonstrated that bone morphogenetic protein can accelerate the healing process when a tendon graft is transplanted into a bone tunnel.

Turf-toe: an analysis of metatarsophalangeal joint sprains in professional football players.

Metatarsophalangeal joint injuries of the great toe (turf-toe) are receiving increasing attention in the literature because of the prevalence of synthetic surfaces and lighter, more flexible shoes. Eighty active professional football players were evaluated. The mechanism of injury was hyperextension in 85% of the players. Eighty-three percent reported their initial injury on artificial turf (P less than 0.05). Other factors significantly related to the incidence of turf-toe included player age (P less than 0.01), number of years in professional football (P less than 0.01), and range of ankle dorsiflexion (P less than 0.05). Turf-toe injury resulted in significantly decreased range of motion of the first metatarsophalangeal joint (P less than 0.01).

Tissue-engineered ligament: cells, matrix, and growth factors.

Current treatment modalities for anterior cruciate ligament (ACL) tears rely on the use of grafts for reconstruction. Treatment can be divided into three categories: autografts, allografts, and synthetic graft replacements. The varied success rates and associated advantages and disadvantages of each method have resulted in controversy as to the best treatment for ACL injuries.

Meniscal injury and repair: clinical status.

Repair or resection of meniscal injuries is one of the most common operative procedures in orthopedics today. A variety of techniques for reconstruction have been attempted and experts are still unsure which treatment of meniscal lesions is best. This article reviews different techniques of meniscal repair and some novel approaches that may be used for treatment of meniscal lesions in the coming years.

Arthroscopic meniscal repair with use of the outside-in technique.

The outside-in technique of arthroscopic repair is effective for repair of most meniscal tears. The overall indications for the use of this technique are similar to those for the commonly used inside-out technique. The outside-in technique is especially useful for suturing the anterior horn of the meniscus as well as for suturing meniscal replacement devices such as a collagen meniscal implant or a meniscal allograft. Other specific advantages of this technique include the ability to predictably avoid neurovascular injury without the need for a large posterior incision. A particular disadvantage is the difficulty of achieving perpendicular orientation of sutures when a tear is adjacent to the site of attachment of the posterior horn. Use of the inside-out technique or an all-inside implant is suggested for these tears. The use of this suturing technique is facilitated by attention to several technical points. The knee should be maintained in flexion for repair of tears of the lateral meniscus (to avoid injury to the peroneal nerve) and in nearly full extension for repair of the posterior aspect of the medial meniscus (to avoid injury to the saphenous nerve and its branches). Care must be taken to avoid tying the sutures around a branch of the saphenous nerve during repair of the medial meniscus. The sutures should be retrieved through a cannula in the anterior portal to avoid the entrapment of the sutures in soft tissue. A probe can be used to prevent displacement of the inner fragment of a bucket handle tear when the needles are placed across the tear, as the entering needles may push the torn fragment into the knee. A vertical suture orientation is preferred in order to evenly co-apt the meniscus to the capsule. If knot-end sutures (so-called Mulberry knots) are used, 2 sutures can be vertically stacked, with 1 on each surface of the meniscus. If a mattress suture is used, a vertical orientation is easily achieved with the outside-in technique. Use of an exogenous fibrin clot is suggested for isolated tears. The clot can be secured to the site of repair by a suture that has been placed through a spinal needle with the outside-in method. Delayed weightbearing should be considered as postoperative management for patients who have had repair of a tear with a radial component or repair of a complex tear in which a fibrin clot was used. Previous studies have demonstrated that the location of the tear and the condition of the anterior cruciate ligament are important factors in determining the success of meniscal repair. The overall results with use of the outside-in technique are comparable with those reported with use of the inside-out method. Patients with concomitant tears of the medial meniscus and the anterior cruciate ligament should have combined meniscal repair and reconstruction of the anterior cruciate ligament. As healing was demonstrated in 8 of 13 patients with an unrepaired tear of the anterior cruciate ligament, consideration should still be given to meniscal repair in patients who refuse reconstruction of the anterior cruciate ligament. In this setting, it may be advisable to use multiple permanent sutures, and the patient must be counseled regarding the higher rate of failure with this approach. Repairs of the lateral meniscus have a higher rate of success, and repair of the lateral meniscus should be considered even in the presence of injury of the anterior cruciate ligament.

Injury and repair of tendons and ligaments.

Tendons and ligaments are fibrous connective tissues that facilitate stability and motion of joints. Significant dysfunction and disability may result from suboptimal healing of tendon and ligament injuries. Extensive research continues to further understand the complex healing pathways that are involved when these structures are damaged. The combination of advances in tissue engineering, surgery, and rehabilitation will provide new pathways of improving tendon and ligament healing.

Knee pain in competitive swimming.

The high volume of training in competitive swimming results in cumulative overload injuries. Knee pain ranks second to shoulder pain as a common complaint in competitive swimmers. Most knee pain occurs on the medial side of the knee and, most commonly, in breaststroke swimmers; however, knee pain may accompany all strokes. This article reviews the incidence of knee pain, the biomechanic and anatomic factors predisposing to injury, specific injury patterns, injury diagnosis, and the treatment and prevention of injury to the knee in swimmers.

Meniscal repair using the outside-to-inside technique.

Research during the past decade has elucidated the structure and function of the knee joint meniscus, and both clinical and experimental studies have demonstrated the importance of this structure. Recent advances, such as the use of an exogenous fibrin clot, have allowed preservation of an increasingly greater proportion of injured menisci. The success of these methods will be established only by long-term follow-up studies demonstrating a lower incidence of progression to degenerative joint disease. It is hoped that an increasing understanding meniscal fibrochondrocytes biology and response to injury will result in the development of novel therapeutic strategies for repair of the injured meniscus. Basic studies clearly have demonstrated that meniscal fibrochondrocytes possess intrinsic repair capability. Both in vitro cell culture studies and in vivo animal models have provided the basic scientific foundation for the use of fibrin clot in tears in the avascular portion of the meniscus. The use of fibrin clot has allowed further expansion of the proportion of meniscal tears that are potentially reparable. Tears in the central, avascular zone of the meniscus, formerly thought to be irreparable, now may undergo repair with an enhanced opportunity for healing. The factors associated with a good prognosis in the meniscal repair include acute tear; peripheral tear; a stable knee; and the presence of serum or factors derived from serum, such as the presence of a fibrin clot, or vascular access channel, or hemarthrosis. Cell culture and molecular biologic techniques currently are being used to improve our understanding of meniscal biology. Particular challenges for future research include determination of the source of the reparative cells in meniscal repair, exploration of the biomechanical properties of the reparative tissue, and demonstration of the potential use of growth factors in meniscal healing. A further potential use of fibrin clot in the future is as a carrier vehicle both for the delivery of growth factors to injured meniscal and for the transplantation of autogenous fibrochondrocytes in meniscal defects. Other avenues of investigation include the use of cytokines to enhance meniscal healing, studies of meniscal replacement with allografts and collagen-based prostheses for meniscal regeneration, and the potential to augment meniscal cell proliferation and matrix synthesis by gene therapy techniques.