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.

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.

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.

The effect of immobilization on the native and repaired tendon-to-bone interface.

BACKGROUND: Little is known of the cellular events that occur in native or repaired tendons as a result of immobilization after injury. To examine this issue, we compared (1) native tendons without immobilization, (2) native tendons with immobilization, and (3) surgically repaired tendons with immobilization. METHODS: Eighty-one rats underwent either patellar tendon repair followed by immobilization or immobilization of the native tendon without repair. A custom external fixation device was used for immobilization. The tendon-bone insertion site was evaluated after two and four weeks of immobilization with use of histologic, radiographic, and biomechanical analyses. RESULTS: Immobilization of the native tendon led to a significant decrease in the load to failure (p < 0.01) and stiffness (p < 0.05) compared with the native tendon at both two and four weeks. The repaired/immobilized group had a significantly lower load to failure at two weeks compared with the native/immobilized group (p < 0.05); however, by four weeks, the repaired group was significantly stronger (p < 0.01). Micro-computerized tomography demonstrated no significant differences in bone microstructure at two weeks but demonstrated increased bone mineral density and bone volume fraction in the repaired/immobilized group at four weeks. There was significantly more MMP-13 (matrix metalloproteinase-13) staining in the native/immobilized specimens compared with the native specimens at both time points (p < 0.01). CONCLUSIONS: Immobilization had a significant detrimental effect on the bone-tendon complex. At two weeks there was a significant decrease in the mechanical properties of the native tendon, but the immobilized, native tendon remained significantly stronger than the repaired and immobilized tendon. However, four weeks of immobilization led to a significant loss of strength of the bone-tendon complex in the native tendon, such that it was significantly weaker than the repaired and immobilized tendon. Surgeons who manage patients with immobilization should be aware of the changes at the bone-tendon complex.

[The effect of osteoprotegerin on tendon-bone healing after reconstruction of the anterior cruciate ligament: a histomorphological and radiographical study in the rabbit]. / Der Einfluss von Osteoprotegerin auf die Sehne-zu-Knochen-Heilung nach Rekonstruktion des vorderen Kreuzbandes: Eine histomorphologische und radiographische Studie im Kaninchenmodell.

AIM: Improvement of the bony incorporation of a soft-tissue graft after ACL reconstruction by local administration of Osteoprotegerin between the bone and tendon graft. METHOD: Fifteen New Zealand White rabbits underwent unilateral anterior cruciate ligament (ACL) reconstruction using an autologous semitendinosis tendon graft. We compared the effect of three OPG doses (5 microg, 50 microg, or 100 microg) at the tendon-bone interface to the controls (OPG carrier) and ACL reconstruction only. Specimens were analyzed at 3 weeks using radiology, histology and histomorphometry to investigate the effect of OPG on the bony incorporation of the tendon graft. RESULTS: Animals treated with OPG 100 microg had a significant (p = 0.007) increase in newly-formed bone around the graft compared to the control group (0.16 +/- 0.01 mm(2); 0.06 +/- 0.02 mm(2)). No significant differences were found between the controls and the other groups (tendon graft only, OPG 5 microg, and 50 microg) (p > 0.05). Bone mineral density, measured in image-pixel brightness (IPB; reference range: 0-255), along the edge of the bone tunnel was greater in the OPG 100 microg group (169.5 +/- 5.9 IPB) compared to the control group (150.3 +/- 4.3 IPB) but this was not statistically significant (p = 0.083). There was a significant decrease in the number of osteoclasts per high-power microscopic fields (HPF) lining the bone tunnel in the OPG 100 microg group compared to the control group (4.4 +/- 2.5 cells/HPF; 6.4 +/- 1.8 cells/HPF) (p = 0.022). No significant differences were found between the control group and the other groups in osteoclast numbers (p > 0.05). CONCLUSION: Since tendon-bone healing requires new bone formation and bone ingrowth around a tendon graft, OPG may improve biologic graft fixation. A potential implication could be earlier return to function or better conditions in revision surgery.

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.

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.

The anatomy and histology of the rotator interval capsule of the shoulder.

Forty-seven rotator interval regions from fetuses and 10 fresh-frozen rotator interval regions from adult cadavers were evaluated by gross dissection and light microscopy. Specimens from adults also were evaluated with ultrasound and magnetic resonance imaging. An analysis of 37 fetal specimens (> 14 weeks gestation) revealed two rotator interval types: Type I (9 of 37) was defined by a contiguous bridge of capsule consisting of poorly organized collagen fibers. A Type II rotator interval (28 of 37) had a complete defect covered by only a thin layer of synovium. Similar to the Type II rotator interval in the fetus, a rotator interval defect was present in six of eight specimens from adults. Histologically, the capsular tissue within the rotator interval consisted of poorly organized collagen fibers in specimens from the fetus and adult. Maximal opening of the rotator interval was seen by ultrasound with internal rotation and downward traction of the hyperextended arm in the coronal, oblique, and sagittal planes. Magnetic resonance imaging of the rotator interval region permitted anatomic evaluation. The complete absence of tissue in 28 of 37 fetuses suggests that the rotator interval defect is congenital. The authors recommend that surgeons carefully evaluate the integrity of the tissue within the rotator interval. When rotator interval closure is desired such as in patients with a persistent sulcus sign after arthroscopic stabilization, suturing the edges of more substantial tissue immediately adjacent to the boundaries of the rotator interval region would seem prudent.

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.

Stability of the lumbar spine after intradiscal electrothermal therapy.

OBJECTIVE: To assess the stability of the human lumbar cadaveric spinal motion segment before and after treatment with intradiscal electrothermal therapy (IDET). DESIGN: An in vitro biomechanic analysis of 5 human cadaveric spinal motion segments by using nondestructive biomechanic testing in flexion/extension, lateral bending, and axial rotation with loads of 0N, 600N, and 1200N. SETTING: University-based hospital research center. CADAVERS: Spinal unit specimens (upper and middle lumbar) from 5 human cadavers (age range, 39-79yr). INTERVENTIONS: A spinal catheter consisting of a thermal-resistive heating coil was placed circumferentially into the outer annulus by using the standard extrapedicular discographic technique through a 17-gauge introducer needle. The disc was then heated in a saline bath (37 degrees C) from 65 degrees C up to 90 degrees C for a total of 17 minutes. MAIN OUTCOME MEASURE: The stability of the spinal segments was measured before and shortly after IDET. Stability of the spine was measured as the compliance of the spine (the angular deformation afforded by the spine under applied bending moments). RESULTS: With increasing preloads, there is a decrease in motion of the spinal segment in all planes of testing. However, there was no significant difference (p >.05) in the stability of the lumbar spine before and after treatment with IDET. CONCLUSIONS: IDET does not destabilize the spinal motion segment in vitro.

The effect of cytokines on the migration of fibroblasts derived from different regions of the canine shoulder capsule.

This study examined the effect of several cytokines on the chemotactic migration of fibroblasts derived from 3 different parts of the canine shoulder: the upper part of the medial glenohumeral ligament (equivalent to the anterior part of the inferior glenohumeral ligament of the human shoulder); the inferior part of the medial glenohumeral ligament (equivalent to the axillary pouch of the human shoulder); and the posterior capsule (equivalent to the thin posterior capsule in the human shoulder). Platelet-derived growth factor-AB stimulated the migration of all 3 cell types in a dose-dependent manner, with increases from 150% to 300% at 1 ng/mL to 500% to 700% at 10 ng/mL. Hepatocyte growth factor also stimulated the migration of all 3 cell types in a dose-dependent manner (130% to 310%). Insulinlike growth factor-1 increased the migration of all 3 types of fibroblasts by 160% to 250%. Bone morphogenic protein-2, interleukin-1, and transforming growth factor-b had no significant effect on migration of shoulder capsular fibroblasts. These data demonstrate that capsular fibroblasts are responsive to specific growth factors and suggest the potential for use of growth factors to augment healing and/or remodeling of the shoulder capsule.

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.

The developmental anatomy of the neonatal glenohumeral joint.

The embryologic development of the capsular ligaments, synovial lining, rotator cuff, and bony structures of the shoulder is incompletely understood. The purpose of this study is to report the gross and microscopic anatomy of the developing glenohumeral joint on the basis of dissections of fetal shoulder specimens. After Institutional Review Board approval from our hospital, 51 shoulders in 37 fetal specimens were obtained from cases of fetal demise. The gestation time of these specimens ranged from 9 to 40 weeks. The morphology of the capsule, labrum, and associated ligaments were studied by dissection under a dissecting microscope. High-resolution radiographs were made, and sections were processed for routine histology. There was noted to be minimal variation in the shape and slope of the acromion. The coracoid was much larger in relation to the shoulder than in the mature shoulder. The coracoacromial ligament was grossly evident at this stage of development, with distinct anterolateral and posteromedial bands in this ligament. The inferior glenohumeral ligament was seen as a prominent thickening in the capsule, whereas the middle and superior glenohumeral ligaments were thinner and more difficult to identify as distinct structures. Upon histologic examination, the inferior glenohumeral ligament was seen to consist of several layers of organized collagen fibers. The inferior glenohumeral ligament inserted into the labrum and margin of the glenoid. The capsule was much thinner in the region superior to the inferior glenohumeral ligament. A rotator interval capsular defect was often present, and the coracohumeral ligament was seen as a distinct structure as early as 15 weeks. A bare spot in the glenoid was not observed. This study indicates that some of the important functional elements of the structure of the mature human shoulder are present early in development, including the glenohumeral and coracohumeral ligaments. The coracoacromial ligament plays a significant role in the formation of the coracoacromial arch in the neonatal shoulder. The presence of a capsular rotator interval indicates that this aspect of capsular anatomy is congenital.

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.

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.

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.

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.