Multi-vendor multi-site quantitative MRI analysis of cartilage degeneration 10 Years after anterior cruciate ligament reconstruction: MOON-MRI protocol and preliminary results.

OBJECTIVE: To describe the protocol of a multi-vendor, multi-site quantitative MRI study for knee post-traumatic osteoarthritis (PTOA), and to present preliminary results of cartilage degeneration using MR T1ρ and T2 imaging 10 years after anterior cruciate ligament reconstruction (ACLR). DESIGN: This study involves three sites and two MR platforms. The patients are from a nested cohort (termed as Onsite cohort) within the Multicenter Orthopaedic Outcomes Network (MOON) cohort 10 years after ACLR. Phantoms and controls were scanned for evaluating reproducibility. Cartilage was automatically segmented, and T1ρ and T2 were compared between operated, contralateral, and control knees. RESULTS: Sixty-eight ACL-reconstructed patients and 20 healthy controls were included. In phantoms, the intra-site coefficients of variation (CVs) of repeated scans ranged 1.8-2.1% for T1ρ and 1.3-1.7% for T2. The inter-site CVs ranged 1.6-2.1% for T1ρ and 1.1-1.4% for T2. In human subjects, the intra-site scan/rescan CVs ranged 2.2-3.5% for T1ρ and 2.6-4.9% for T2 for the six major compartments. In patients, operated knees showed significantly higher T1ρ and T2 values mainly in medial femoral condyle, medial tibia and trochlear cartilage compared with contralateral knees, and showed significantly higer T1ρ and T2 values in all six compartments compared to healthy control knees. The patient contralateral knees showed higher T1ρ and T2 values mainly in the lateral femoral condyle, lateral tibia, trochlear, and patellar cartilage compared to healthy control knees. CONCLUSION: A platform and workflow with rigorous quality control has been established for a multi-vendor multi-site quantitative MRI study in evaluating PTOA 10 years after ACLR. Our preliminary report suggests significant cartilage matrix changes in both operated and contralateral knees compared with healthy control knees.

KOOS pain as a marker for significant knee pain two and six years after primary ACL reconstruction: a Multicenter Orthopaedic Outcomes Network (MOON) prospective longitudinal cohort study.

OBJECTIVE: The prevalence of radiographic osteoarthritis (OA) after anterior cruciate ligament reconstruction (ACLR) approaches 50%, yet the prevalence of significant knee pain is unknown. We applied three different models of Knee injury and Osteoarthritis Outcome Score (KOOS) thresholds for significant knee pain to an ACLR cohort to identify prevalence and risk factors. DESIGN: Multicenter Orthopaedic Outcomes Network (MOON) prospective cohort patients with a unilateral primary ACLR and normal contralateral knee were assessed at 2 and 6 years. Independent variables included patient demographics, validated Patient Reported Outcomes (PRO; Marx activity score, KOOS), and surgical characteristics. Models included: (1) KOOS criteria for a painful knee = quality of life subscale <87.5 and ≥2 of: KOOSpain <86.1, KOOSsymptoms <85.7, KOOSADL <86.8, or KOOSsports/rec <85.0; (2) KOOSpain subscale score ≤72 (≥2 standard deviations below population mean); (3) 10-point KOOSpain drop from 2 to 6 years. Proportional odds models (alpha ≤ 0.05) were used. RESULTS: 1761 patients of median age 23 years, median body mass index (BMI) 24.8 kg/m(2) and 56% male met inclusion, with 87% (1530/1761) and 86% (1506/1761) follow-up at 2 and 6 years, respectively. At 6 years, n = 592 (39%), n = 131 (9%) and n = 169 (12%) met criteria for models #1 through #3, respectively. The most consistent and strongest independent risk factor at both time-points was subsequent ipsilateral knee surgery. Low 2-year Marx activity score increased the odds of a painful knee at 6 years. CONCLUSIONS: Significant knee pain is prevalent after ACLR; with those who undergo subsequent ipsilateral surgery at greatest risk. The relationship between pain and structural OA warrants further study.

Meniscus treatment and age associated with narrower radiographic joint space width 2-3 years after ACL reconstruction: data from the MOON onsite cohort.

OBJECTIVE: To identify risk factors for radiographic signs of post-traumatic osteoarthritis (OA) 2-3 years after anterior cruciate ligament (ACL) reconstruction through multivariable analysis of minimum joint space width (mJSW) differences in a specially designed nested cohort. METHODS: A nested cohort within the Multicenter Orthopaedic Outcomes Network (MOON) cohort included 262 patients (148 females, average age 20) injured in sport who underwent ACL reconstruction in a previously uninjured knee, were 35 or younger, and did not have ACL revision or contralateral knee surgery. mJSW on semi-flexed radiographs was measured in the medial compartment using a validated computerized method. A multivariable generalized linear model was constructed to assess mJSW difference between the ACL reconstructed and contralateral control knees while adjusting for potential confounding factors. RESULTS: Unexpectedly, we found the mean mJSW was 0.35 mm wider in ACL reconstructed than in control knees (5.06 mm (95% CI 4.96-5.15 mm) vs 4.71 mm (95% CI 4.62-4.80 mm), P < 0.001). However, ACL reconstructed knees with meniscectomy had narrower mJSW compared to contralateral normal knees by 0.64 mm (95% C.I. 0.38-0.90 mm) (P < 0.001). Age (P < 0.001) and meniscus repair (P = 0.001) were also significantly associated with mJSW difference. CONCLUSION: Semi-flexed radiographs can detect differences in mJSW between ACL reconstructed and contralateral normal knees 2-3 years following ACL reconstruction, and the unexpected wider mJSW in ACL reconstructed knees may represent the earliest manifestation of post-traumatic osteoarthritis and warrants further study.

The central ACL defect as a model for failure of intra-articular healing.

Intra-articular soft tissues, such as the anterior cruciate ligament (ACL), fail to heal in contrast to the extra-articular medial collateral ligament (MCL), which undergoes classic healing. The goal of this study was to validate a model for failure of intra-articular healing that could be used in the future to test new repair strategies. We conducted a two-part experiment, the first part ex vivo, and the second in vivo. Our initial ex vivo experiments were used to determine the optimal width of the central defect in the canine ACL that would produce reproducible structural properties at time zero. The second experimental series used this optimal scalpel blade width to create a central defect in the canine ACL followed by measurement of structural properties in the ACL after either a 3- or 6-week in vivo healing period. A 3.5-mm beaver blade resulted in a maximum tolerated load of 56.8 +/- 4.7% (mean +/- SEM) of control at time zero. After the 3- and 6-week in vivo healing periods, the maximum load was 74.6 +/- 5.3 at 3 weeks and 64.9 +/- 3.8% at 6 weeks compared to control. Thus, biomechanical parameters tested at 6 weeks after creation of a defect showed no significant gains from defects tested immediately after the creation of injury. The centrally placed ACL defect in this canine model demonstrates failure to mechanically heal, which should prove suitable for future in vivo evaluation of the biomechanical and histological response to tissue engineering repair strategies for intra-articular soft tissues.

Collagen expression and biomechanical response to human recombinant transforming growth factor beta (rhTGF-beta2) in the healing rabbit MCL.

We investigated biomechanical and collagen expression in a healing bilateral rabbit medial collateral ligament (MCL) model to human recombinant transforming growth factor beta (rhTGF-beta2) at three and six weeks. Each rabbit had rhTGF-beta2 in a bioabsorbable pellet administered in one side, with the contralateral side serving as control (no rhTGF-beta2). All MCL healed with rhTGF-beta2 producing a profoundly increased scar mass at three weeks which decreased in size toward control at six weeks. In-situ hybridization demonstrated collagen expression (type I and III) no different than control at three weeks, but by six weeks elevated expression of type I was seen. Biomechanical analysis at three weeks showed no effect of rhTGF-beta2 on structural properties. However, at six weeks rhTGF-beta2 significantly inhibited both the maximum load (p < 0.05) and energy absorbed (p < 0.05) with no change in stiffness. Despite increased type I collagen expression and profound increase in early scar mass, rhTGF-beta2 did not improve the structural properties. Whether the dose or mode of delivery is responsible for decline in structural properties cannot be determined in this design. We hypothesize investigations of healing ligaments to cytokines should have biologic and biomechanical properties correlated in the same study at a minimum of two time points.

Assessment and management of the painful shoulder.

The shoulder joint is a complex structure composed of intricate bony architecture and an ornate system of muscles, tendons, and ligaments. What many refer to as the "shoulder joint" is actually a combination of 4 articulations--the glenohumeral joint, acromioclavicular joint, sternoclavicular joint, and the scapulothoracic articulation. These structures work together to provide the shoulder complex with multiple degrees of freedom, which allow the upper extremity to be abducted, adducted, rotated, flexed, and extended. Although this flexibility is vital for positioning the arm in space, it can make the evaluation of pathology difficult. Furthermore, neck pathology can refer pain to the shoulder, which may require a screening evaluation of the neck. This article reviews the relevant anatomy and discusses an approach to the differential diagnosis of shoulder pain.

Cryotherapy: an effective modality for decreasing intraarticular temperature after knee arthroscopy.

Cryotherapy is a modality commonly used after arthroscopic procedures. We divided 17 patients into two groups after routine knee arthroscopy: 12 patients were immediately treated with ice and 5 control patients were treated without ice for the first hour. In all patients, thermocouple probes were placed intraarticularly into the lateral gutter of the knee. Ice was placed on the operative knees of the treatment group for 2 hours. The control group had no intervention for the 1st hour and then had ice applied for the 2nd hour. Temperatures were continually recorded every minute for 2 hours. The temperature in the treatment group declined significantly, by 2.2 degrees C (95% confidence interval [-3.6 degrees C, -0.72 degrees C]) over the 1st hour and by 0.79 degrees C (95% CI [-1.8 degrees C, 0.18 degrees C]) over the 2nd hour (P = 0.008). The temperature in the control group increased significantly, by 5.0 degrees C (95% CI [2.4 degrees C, 7.5 degrees C]) over the 1st hour (P = 0.006). After ice was applied, the temperature fell significantly, by 4.0 degrees C (95% CI [-8.3 degrees C, 0.26 degrees C]) (P = 0.06). The difference between the temperature decrease in the treatment group and the increase in the control group at 60 minutes was 7.1 degrees C. This is the first rigorously conducted study in human patients that documents a statistically significant decline in intraarticular knee temperature with the application of ice and compression to the skin. The mechanism by which cryotherapy acts must therefore include the cooling effect on the intraarticular environment and synovium.

Does intraarticular morphine improve pain control with femoral nerve block after anterior cruciate ligament reconstruction?

In a prospective, randomized, double-blinded manner, we compared the effects of a preoperative intraarticular injection of morphine (5 mg) or a placebo, combined with a postoperative femoral nerve block, on postoperative pain. Sixty-two patients underwent an arthroscopically assisted anterior cruciate ligament reconstruction using patellar tendon autograft under general anesthesia. No statistical difference between the two groups was evident in terms of age, sex, weight, operative time, volume of bupivacaine received with the femoral nerve block, or tourniquet use or tourniquet time. Comparison of visual analog scale pain scores revealed no statistical difference between the groups at any point after the operation. Both groups had a significant decrease in visual analog scale scores after the femoral nerve block, with the lowest mean values 4 hours after the operation (morphine group, 1.7; placebo group, 1.4), and continuing to be significantly less through 24 hours (morphine, 2.6; placebo, 2.9). No significant difference in postoperative narcotic medication use was evident in the recovery room or at home. A post hoc power analysis revealed that the study power reached 87%, with a significance level of 5%. The postoperative femoral nerve block was effective, and intraarticular morphine provided no additional benefit.

Clinical outcome of isolated subcortical trabecular fractures (bone bruise) detected on magnetic resonance imaging in knees.

Isolated subcortical trabecular bone injury (bone bruise) has rarely been described. Our purpose is to report a series of patients who had a history of traumatic injury, knee effusion, normal radiographs, and initial equivocal physical examination for ligament and meniscal integrity, and who were found to have isolated injury of the trabecular bone on magnetic resonance imaging. We evaluated demographic data, physical examination findings, radiographs, magnetic resonance imaging, and clinical outcome for 23 patients. Follow-up data included time to return to preinjury activity level, International Knee Documentation Committee activity level rating before and after injury, and postinjury Lysholm scores. All magnetic resonance imaging scans were negative for associated grade III meniscal lesions and ligament injury. Time to return to preinjury activity level was under 7 months in 96% of the patients. Postinjury International Knee Documentation Committee rating was unchanged in 91% of patients. Postinjury Lysholm score was 90 or more in 91% of patients. We propose that the recognition of these injuries is important because magnetic resonance imaging can distinguish them from meniscal or ligament injury requiring surgical intervention (arthroscopy). If detected on magnetic resonance imaging as an isolated injury, surgical arthroscopy is unnecessary since these patients can be expected to recover well in the short term with restricted weightbearing and initial activity modification.

Analgesia with femoral nerve block for anterior cruciate ligament reconstruction.

Anterior cruciate ligament reconstruction is performed routinely as an outpatient surgical procedure despite few studies of patient acceptance or postoperative patient analgesia. This study reports the first series of postoperative femoral nerve blocks as analgesia for outpatient anterior cruciate ligament reconstruction. The authors retrospectively reviewed 161 patients undergoing two incision arthroscopically assisted autograft middle 1/3 patellar tendon anterior cruciate ligament reconstruction on an out-patient basis at the authors' institution during a period of 30 months. Hospital and anesthesia records were reviewed, and 83% of patients were contacted retrospectively to survey their perceptions of the procedure and its outcome. Ninety-eight percent of the patients were discharged from the ambulatory surgery center, with 51% discharged the same day as the surgery and 47% discharged by 7:00 AM the next day. As the study progressed, the number of patients staying overnight was reduced by 50%. Ninety-eight percent of patients surveyed found femoral nerve block to be beneficial, and the same percentage thought the discharge time was appropriate. However, 69% of patients staying overnight cited reasons other than pain as factors in their stay. No significant complications were reported. Based on these results, the administration of a femoral nerve block is recommended for patients undergoing outpatient anterior cruciate ligament reconstruction because it is a highly effective form of analgesia with an excellent degree of patient satisfaction.

Prospective evaluation of history and physical examination: variables to determine radiography in acute ankle injuries.

OBJECTIVE: This study investigated history and physical findings among 74 patients with acute ankle injuries in order to determine factors significantly associated with fractures, excluding avulsion fragments < 3 mm in size, and syndesmosis injuries and to determine factors that necessitate radiography. DESIGN: This was a prospective study performed during a 12-month period. After recording history and physical examination data, a gestalt prediction of a positive or negative radiographic result was made before the patient underwent ankle radiography. Analysis then determined factors important for radiography. PATIENTS AND SETTING: Patients who presented to a sports medicine center with an acute ankle injury were enrolled in the study after meeting the enrollment criteria. MAIN OUTCOME MEASURES: Before analysis, predictions for injury were based on accepted indicators. Outcome measures, factors that would indicate the need for radiography, were formulated after data collection and statistical analysis. RESULTS: Radiographic findings showed nine fractures and three widened syndesmoses as well as 15 minor ligamentous avulsions. Statistical analysis showed significant association (p < 0.05) of fracture with previous ankle fracture, syndesmosis pain with external rotation stress testing, and pain along the middle third of the distal fibula, from anterior to posterior. Syndesmosis injuries had a significant association with pain during external rotation stress testing. CONCLUSIONS: Although additional investigation with larger patient numbers would be beneficial, this study highlights the importance of history of previous fracture, pain on the distal mid-fibula or mid-tibia, and pain with external rotation. Furthermore, if these three variables are prospectively applied as criteria for radiography, a 55% reduction in radiography would result with 100% sensitivity. Finally, experienced sports medicine physicians had a 100% sensitivity, 68% specificity, 100% negative predictive value, and 39% positive predictive value for prediction of clinically significant fractures or syndesmosis injuries.

Expression of collagen and matrix metalloproteinases in ruptured human anterior cruciate ligament: an in situ hybridization study.

The biological basis for failure of the human anterior cruciate ligament to heal after rupture is unknown. Since this failure could be influenced by abnormalities in matrix protein production or degradation, or both, several diverse matrix protein markers were utilized to survey the state of these extracellular proteins in intrinsic anterior cruciate ligament fibroblasts. Matrix gene expression was visualized by in situ hybridization 9 to 365 days after rupture using probes for type-I collagen, collagenase, 72kDa-gelatinase, and tissue inhibitor of metalloproteinase. Remnants of anterior cruciate ligament were biopsied arthroscopically from 20 patients at reconstruction, fixed in 4% paraformaldehyde, and processed with cDNA probes for the aforementioned mRNAs. mRNA expression of type-I collagen was detected in all specimens, was equally distributed throughout the remnants, and remained evident even at 1 year after injury. Neither of the matrix-degrading enzymes nor their inhibitor (tissue inhibitor of metalloproteinase) was expressed at substantial levels at any time point. Collagen expression within the anterior cruciate ligament confirmed the viability of the ligament remnants for as long as 1 year after rupture. The lack of significant expression of the two matrix-degrading metalloproteinases by the fibroblasts is not consistent with an autodegradation of the remaining ruptured ligament tissue, and whether the lack of matrix remodelling may account, at least in part, for the poor healing response of the anterior cruciate ligament remains to be determined. This initial investigation by in situ hybridization techniques provides a descriptive profile of matrix gene expression in the damaged human anterior cruciate ligament.

Stress fractures in skeletally immature patients.

Stress fractures are a common injury in an active population. As children become increasingly involved in organized sports, the recognition of stress fractures and differentiation from infections or neoplasms requires a knowledge of their most common sites, presentation, and clinical course. We retrospectively reviewed 34 stress fractures in 32 skeletally immature patients from June 1977 to May 1993. Age, fracture location, treatment, time to union or healing, associated conditions, complications, radiographs, and clinical outcome were recorded. Fifty percent of patients were involved in sports; the most common complaint was pain with activity. The most common site was the tibia (47%) followed by the fibula (21%) and femur (12%). All had resolution of symptoms and returned to normal activity. All but two healed with either activity modification or cast immobilization. The radiographic findings included early periosteal callus formation that rapidly consolidated to new bone on serial studies. A careful history, physical examination, and radiographs can help diagnose most common stress fractures in the skeletally immature individual and can differentiate stress fractures from infection or neoplasm with appropriate conservative treatment.

Patellar tendon and anterior cruciate ligament have different mitogenic responses to platelet-derived growth factor and transforming growth factor beta.

The healing responses of the anterior cruciate ligament and the patellar tendon differ markedly. The anterior cruciate ligament fails to heal, whereas the patellar tendon heals slowly. The basis of these differences is unknown. Since cellular proliferation is a critical element of healing, we investigated the response to explants of anterior cruciate ligament and patellar tendon from sheep knees to platelet-derived growth factor-AB and transforming growth factor beta 1 as a function of time and dose. Explants cultured for 48, 72, and 96 hours with transforming growth factor beta 1 (0-100 ng/ml) or platelet-derived growth factor-AB (0-200 ng/ml) were radiolabeled for the final 24 hours with [3H]thymidine, and DNA synthesis was quantified as trichloroacetic acid-precipitable radioactivity normalized to dry tissue weight. Statistical analyses (analysis of variance) showed that transforming growth factor beta 1 induced a significant proliferative response in the anterior cruciate ligament at 96 hours with equivalent responses at 10, 50, and 100 ng/ml, whereas the patellar tendon only responded to one condition, 10 ng/ml at 96 hours. Conversely, the patellar tendon had a significant dose-dependent response to platelet-derived growth factor-AB at 72 and 96 hours, whereas the anterior cruciate ligament showed no proliferative response to platelet-derived growth factor-AB. The minimal response of anterior cruciate ligament to platelet-derived growth factor-AB could explain, at least in part, the poor repair capacity of this tissue. The response of the anterior cruciate ligament to transforming growth factor beta suggests that exogenous transforming growth factor beta may promote initial healing. Although growth factors have the potential to modulate soft-tissue repair, tissue responses in tendons and ligaments may vary at different anatomic sites.

Distribution of cellular repopulation and collagen synthesis in a canine anterior cruciate ligament autograft.

Whether the central core of an anterior cruciate ligament autograft reconstruction is nutritionally compromised at a time when revascularization is known to be complete has not been determined by methods that detect matrix synthesis. In a canine model of anterior cruciate ligament reconstruction with patellar tendon autograft, the adequacy of the supply of metabolites for cellular matrix synthesis was determined by autoradiographic analysis. Total collagen synthesis and cellularity were also quantified. Total collagen synthesis was found to be significantly elevated (p = 0.014 by analysis of variance) in the ligament reconstructions as compared with normal anterior cruciate ligaments or patellar tendons but cellularity was not (p = 0.13 by analysis of variance). Autoradiography demonstrated even distribution of [3H]proline incorporation throughout the graft and normal tissue. When revascularization was complete there was an adequate supply of metabolites for cellular synthesis of protein macromolecules within all regions of the ligament reconstruction. At 3 months after reconstruction, the grafts were found to be actively remodeling their collagen matrix. Since the long-term function of an anterior cruciate ligament autograft is dependent on viable fibroblasts to maintain the collagen matrix the canine anterior cruciate ligament reconstruction contains living cells that are able to remodel the matrix under appropriate conditions.

Femoral nerve block as an alternative to parenteral narcotics for pain control after anterior cruciate ligament reconstruction.

Anterior cruciate ligament (ACL) reconstruction is associated with significant postoperative pain, usually requiring parenteral narcotics. A prospective study of arthroscopically assisted autograft patellar tendon ACLR was initiated using Winnie's "three-in-one" femoral nerve block (FNB) as the primary means of postoperative pain control. Patient satisfaction and absence of parenteral narcotic use indicated clinical success. Of 24 patients studied, 92% had no parenteral narcotics administered following FNB. Ninety-five percent of patients believed FNB was beneficial and would request another. The average duration of pain control was 29 hours and the majority of patients (79%) believed discharge was possible within 23 hours. There were two patients who failed to respond to FNBs (8%) and no major complications. FNB is a safe, reliable, and effective form of analgesia following ACLR, eliminating the need for parenteral narcotics.

Osteomyelitis of the pubic symphysis in athletes: a case report and literature review.

Groin pain is a common problem in athletes. Osteitis pubis, a chronic inflammatory condition involving the pubic symphysis, is a rare cause, and pyogenic osteomyelitis of the pubis is seen even more rarely in healthy athletes. We report one of four cases of pyogenic osteomyelitis of the pubis seen at our institution, review our experience with all four cases, and present a review of the literature (7 cases). The diagnosis is established by the presence of extreme pain, point tenderness at the pubic symphysis, fever, and either a positive culture of blood, needle aspiration, or open biopsy of the pubis. White blood cell count, erythrocyte sedimentation rate, and the results of bone scan and computerized tomography may initially be normal and therefore cannot exclude the diagnosis. Prompt treatment with intravenous (i.v.) antibiotics effective against Staphylococcus aureus (causative organism in all documented cases-9/11) should initially be administered and then guided by culture and sensitivity information. Oral antibiotics should be given if the infection is responsive to i.v. antibiotic treatment. Prompt recognition and treatment with antibiotics may obviate the need for surgical debridement. All athletes who returned to sports activity did so by 6 months after diagnosis.

Regional mitogenic response of the meniscus to platelet-derived growth factor (PDGF-AB).

Since meniscal healing is region-specific, we studied the regional (peripheral compared with central) response of meniscal explants to human, recombinant platelet-derived growth factor-AB. Meniscal explants from the hindlimbs of both knees of mature sheep were sectioned and were cultured with variable doses of human, recombinant platelet-derived growth factor-AB, and incorporation of [3H]-thymidine was measured. The mitogenic response was measured at different times in culture (48 or 96 hours) and by location (lateral or medial). In the absence of the growth factor, the peripheral third of both menisci incorporated 10-fold more [3H]-thymidine on a weight basis than did the central two-thirds. Cellularity was equivalent in the two regions. Doses of less than 100 ng/ml of growth factor produced either no stimulation or a variable response. A dose of 100 ng/ml resulted in consistent, significant (p < 0.05) stimulation in all groups in the peripheral region, and a dose of 200 ng/ml provided more than a 2.5-fold increase. Multiple-factor analysis of variance demonstrated that there were no significant differences between experiments, times in culture, or menisci. The central region did not respond to stimulation with the growth factor at any of the doses tested. These data suggest that regional differences (peripheral compared with central) in responsiveness to human, recombinant platelet-derived growth factor-AB may reflect a different level of signal transduction machinery for growth factor receptors and distinct fibrobchondrocyte populations. These findings are consistent with the variable healing capacity of the meniscal regions in vivo and suggest a pharmacological means to promote the repair of the peripheral meniscal region.

Proliferative responses to platelet-derived growth factor in young and old rat patellar tendon.

Musculoskeletal soft tissue repair is often a slow process that may be complicated by aging, thus we investigated the mitogenic response of young and old rat patellar tendon (PT) explants to platelet-derived growth factor-AB (PDGF-AB). Bilateral PT explants from young (4 months) and old (29 or 36 months) rats of two strains (Fisher 344 and Fisher-Brown-Norway) were cultured for 72 h in platelet-poor horse serum in the presence or absence of 100 ng/ml recombinant human PDGF-AB. The explants were radiolabelled with [3H]-TdR for the final 24 h in culture. Tendon cellularity and DNA synthesis data were analyzed by multiple factor ANOVA (age, strain, and side), Mann-Whitney t-test (cellularity and DNA synthesis), and a sign test (proliferative response to PDGF). Tendon cellularity declined significantly with age in both strains (p < 0.05), while both young and old patellar tendon fibroblasts in both strains had a significant (> 100%) increase in DNA synthesis with the addition of PDGF (p < 0.05). Although there was a trend to lower proliferative responses in older tendons, the differences were not significant. Autoradiographic analysis of labeling indices in F344 tendons showed a diminished responsiveness to PDGF (p < 0.04, ANOVA). Strain and side response on a per cell or tissue weight basis were not significant factors. Under appropriate experimental conditions, these two animal models of aging showed declines in responses to high levels of PDGF, suggesting that the PT reflects an age-dependent diminished capacity for wound repair.