The glenohumeral ligaments: Superior, middle, and inferior: Anatomy, biomechanics, injury, and diagnosis.

The three glenohumeral ligaments (superior, middle, and inferior) are discrete thickenings of the glenohumeral joint capsule and are critical to shoulder stability and function. Injuries to this area are a cause of significant musculoskeletal morbidity. A literature search was performed by a review of PubMed, Google Scholar, and OVID for all relevant articles published up until 2020. This study highlights the anatomy, biomechanical function, and injury patterns of the glenohumeral ligaments, which may be relevant to clinical presentation and diagnosis. A detailed understanding of the normal anatomy and biomechanics is a necessary prerequisite to understanding the injury patterns and clinical presentations of disorders involving the glenohumeral ligaments of the shoulder.

The human meniscus: a review of anatomy, function, injury, and advances in treatment.

Meniscal injuries are recognized as a cause of significant musculoskeletal morbidity. The menisci are vital for the normal function and long-term health of the knee joint. The purpose of this review is to provide current knowledge regarding the anatomy and biomechanical functions of the menisci, incidence, injury patterns and the advancements in treatment options of meniscal injury. A literature search was performed by a review of PubMed, Google Scholar, MEDLINE, and OVID for all relevant articles published between 1897 and 2014. This study highlights the anatomical and biomechanical characteristics of the menisci, which may be relevant to injury patterns and treatment options. An understanding of the normal anatomy and biomechanical functions of the knee menisci is a necessary prerequisite to understanding pathologies associated with the knee.

Burrowing for answers: Investigating Syrian hamster welfare through owner surveys.

BACKGROUND: Syrian hamsters are a relatively common pet species in the UK. However, we know very little about how they are kept. The aim of this study was to identify areas of good and poor practices among Syrian hamster owners using owner surveys. METHOD: A survey of pet hamster owners was conducted with questions on husbandry, behaviour and health. RESULTS: There were 548 survey responses. Over 95% of the owners provided a wheel, hideaway or chew toy, and over 90% housed their hamster alone. However, 18.4% of the owners used hamster balls, hamsters may have been fed a diet that was not entirely appropriate, and over 45% of respondents reported that their hamsters were housed in close proximity to predator species. Most (65.9%) hamsters had never been taken to a veterinarian. Hamster ball use, shallower substrate depth and more frequent handling were significantly associated with greater owner observations of bar biting. LIMITATIONS: A key limitation is that the respondents may not be representative of the average pet hamster owner, so this research does not provide a complete picture of the current state of hamster welfare. CONCLUSION: There are some welfare concerns regarding the way Syrian hamsters are currently kept in the UK. Therefore, attempts to better distribute information about hamster care to owners should be made.

Dynamic contact mechanics of radial tears of the lateral meniscus: implications for treatment.

PURPOSE: To characterize the effect of radial tears (RTs) of the lateral meniscus and their subsequent treatment (inside-out repair, partial meniscectomy) on joint contact mechanics during simulated gait. METHODS: Six human cadaveric knees were mounted on a simulator programmed to mimic human gait. A sensor was inserted below the lateral meniscus to measure peak joint contact pressure location, magnitude, and contact area. The following conditions were compared: intact meniscus, 30% RT (at the popliteal hiatus), 60% RT, 90% RT, repair, and partial meniscectomy. Data were analyzed in the midstance phase of gait (14% and 45%) when axial force was at its highest (2,100 N). RESULTS: Intact knees had peak contact pressures of 5.9 ± 0.9 MPa and 6.4 ± 1.1 MPa at 14% and 45% of gait, respectively. RTs of up to and including 60% had no effect on pressure magnitude or location. RTs of 90% resulted in significantly increased peak pressure (8.4 ± 1.1 MPa) in the postero-peripheral aspect of the tibial plateau and reduced contact area versus the intact knee, at 45% of gait. Repair resulted in a significant decrease in peak pressure (7.7 ± 1.0 MPa) relative to 90% RT but had no effect on contact area. Partial lateral meniscectomy resulted in areas and pressures that were not significantly different from 90% tears (8.7 ± 1.5 MPa). CONCLUSIONS: Simulated large RTs of the lateral meniscus in the region of the popliteal hiatus show unfavorable dynamic contact mechanics that are not significantly different from those resulting from a partial lateral meniscectomy. Pressure was significantly reduced with inside-out repair but was not affected by partial meniscectomy; contact area was not restored to that of the intact condition for either procedure. CLINICAL RELEVANCE: Large RTs in the region of the popliteal hiatus show unfavorable dynamic contact mechanics.

The basic science of the patella: structure, composition, and function.

The patella is the largest sesamoid bone in the body. The patellofemoral joint provides an integral articulating component of the extensor mechanism of the knee joint. A detailed description of patella anatomy, embryology and development, neurovascular anatomy, biomechanical function, and imaging modalities is provided in this article. Common patellar pathologies such as patellar instability, trochlear dysplasia, patella alta and baja, and patellofemoral joint arthritis as well as patellofemoral arthroplasty as a treatment option are also discussed. An understanding of the normal anatomy and biomechanics of the patella is a necessary prerequisite for understanding the pathogenesis of disorders involving the knee.

Femoral neuropathy following total hip arthroplasty: review and management guidelines.

Femoral neuropathy following primary or revision total hip arthroplasty (THA) is a rare but acknowledged complication. Treatment of femoral neuropathy has long been debated and there is a paucity of accepted principles on which to base management. Currently, no definitive management protocol exists in the literature. A literature search was performed by a review of PubMed, Google Scholar and OVID articles published from 1972-2011. The literature reports an incidence rate of femoral neuropathy following THA ranging from 0.1 to 2.4 percent. Determining the precise aetiology, establishing a diagnosis and subsequent treatment of femoral nerve injury remains a difficult task, with conservative management remaining the treatment benchmark. In this review, we aim to summarise the aetiologies and risk factors associated with femoral neuropathy following THA and provide management guidelines.

Factors for severe outcomes following SARS-CoV-2 infection in people with cystic fibrosis in Europe.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with cystic fibrosis (pwCF) can lead to severe outcomes. METHODS: In this observational study, the European Cystic Fibrosis Society Patient Registry collected data on pwCF and SARS-CoV-2 infection to estimate incidence, describe clinical presentation and investigate factors associated with severe outcomes using multivariable analysis. RESULTS: Up to December 31, 2020, 26 countries reported information on 828 pwCF and SARS-CoV-2 infection. Incidence was 17.2 per 1000 pwCF (95% CI: 16.0-18.4). Median age was 24 years, 48.4% were male and 9.4% had lung transplants. SARS-CoV-2 incidence was higher in lung-transplanted (28.6; 95% CI: 22.7-35.5) versus non-lung-transplanted pwCF (16.6; 95% CI: 15.4-17.8) (p≤0.001).SARS-CoV-2 infection caused symptomatic illness in 75.7%. Factors associated with symptomatic SARS-CoV-2 infection were age >40 years, at least one F508del mutation and pancreatic insufficiency.Overall, 23.7% of pwCF were admitted to hospital, 2.5% of those to intensive care, and regretfully 11 (1.4%) died. Hospitalisation, oxygen therapy, intensive care, respiratory support and death were 2- to 6-fold more frequent in lung-transplanted versus non-lung-transplanted pwCF.Factors associated with hospitalisation and oxygen therapy were lung transplantation, cystic fibrosis-related diabetes (CFRD), moderate or severe lung disease and azithromycin use (often considered a surrogate marker for Pseudomonas aeruginosa infection and poorer lung function). CONCLUSION: SARS-CoV-2 infection yielded high morbidity and hospitalisation in pwCF. PwCF with forced expiratory volume in 1 s <70% predicted, CFRD and those with lung transplants are at particular risk of more severe outcomes.

Diabetes mellitus impairs tendon-bone healing after rotator cuff repair.

INTRODUCTION: Studies have demonstrated a significant decrease in skeletal mass, bone mineral density, and impaired fracture healing in the diabetic population. However, the effect of sustained hyperglycemia on tendon-to-bone healing is unknown. MATERIALS AND METHODS: Forty-eight male, Lewis rats underwent unilateral detachment of the supraspinatus tendon followed by immediate anatomic repair with transosseous fixation. In the experimental group (n = 24), diabetes was induced preoperatively via intraperitoneal injection of streptozotocin (STZ, 65 mg/kg) and confirmed with both pre- and post-STZ injection intraperitoneal glucose tolerance tests (IPGTT). Animals were sacrificed at 1 and 2 weeks postoperatively for biomechanical, histomorphometric, and immunohistochemical analysis. Serum hemoglobin A1c (HbA1c) levels were measured at 2 weeks postoperatively. Statistical comparisons were performed using Student t tests with significance set at P < .05. RESULTS: IPGTT analysis demonstrated a significant impairment of glycemic control in the diabetic compared to control animals (P < .05). Mean HbA1c level at 2 weeks postoperatively was 10.6 ± 2.7% and 6.0 ± 1.0% for the diabetic and control groups, respectively (P < .05). Diabetic animals demonstrated significantly less fibrocartilage and organized collagen, and increased AGE deposition at the tendon-bone interface (P < .05). The healing enthesis of diabetic animals demonstrated a significantly reduced ultimate load-to-failure (4.79 ± 1.33 N vs 1.60 ± 1.67 N and 13.63 ± 2.33 N vs 6.0 ± 3.24 N for control versus diabetic animals at 1 and 2 weeks, respectively) and stiffness compared to control animals (P < .05). DISCUSSION: Sustained hyperglycemia impairs tendon-bone healing after rotator cuff repair in this rodent model. These findings have significant clinical implications for the expected outcomes of soft tissue repair or reconstructive procedures in diabetic patients with poor glycemic control.

2-Amino-2,3-dihydro-1H-indene-5-carboxamide-Based Discoidin Domain Receptor 1 (DDR1) Inhibitors: Design, Synthesis, and in Vivo Antipancreatic Cancer Efficacy.

A series of 2-amino-2,3-dihydro-1H-indene-5-carboxamides were designed and synthesized as new selective discoidin domain receptor 1 (DDR1) inhibitors. One of the representative compounds, 7f, bound with DDR1 with a Kd value of 5.9 nM and suppressed the kinase activity with an half-maximal (50%) inhibitory concentration value of 14.9 nM. 7f potently inhibited collagen-induced DDR1 signaling and epithelial-mesenchymal transition, dose-dependently suppressed colony formation of pancreatic cancer cells, and exhibited promising in vivo therapeutic efficacy in orthotopic mouse models of pancreatic cancer.

Design, Synthesis, and Biological Evaluation of 3-(Imidazo[1,2- a]pyrazin-3-ylethynyl)-4-isopropyl- N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide as a Dual Inhibitor of Discoidin Domain Receptors 1 and 2.

Discoidin-domain receptors 1 and 2 (DDR1 and DDR2) are new potential targets for anti-inflammatory-drug discovery. A series of heterocycloalkynylbenzimides were designed and optimized to coinhibit DDR1 and DDR2. One of the most promising compounds, 5n, tightly bound to DDR1 and DDR2 proteins with Kd values of 7.9 and 8.0 nM; potently inhibited the kinases with IC50 values of 9.4 and 20.4 nM, respectively; and was significantly less potent for a panel of 403 wild-type kinases at 1.0 µM. DDR1- and DDR2-kinase inhibition by 5n was validated by Western-blotting analysis in primary human lung fibroblasts. The compound also dose-dependently inhibited lipopolysaccharide (LPS)-induced interleukin 6 (IL-6) release in vitro and exhibited promising in vivo anti-inflammatory effects in an LPS-induced-acute-lung-injury (ALI) mouse model. Compound 5n may serve as a lead compound for new anti-inflammatory drug discovery.

Effect of immediate and delayed high-strain loading on tendon-to-bone healing after anterior cruciate ligament reconstruction.

BACKGROUND: We previously demonstrated, in a rat anterior cruciate ligament (ACL) graft reconstruction model, that the delayed application of low-magnitude-strain loading resulted in improved tendon-to-bone healing compared with that observed after immediate loading and after prolonged immobilization. The purpose of this study was to determine the effect of higher levels of strain loading on tendon-to-bone healing. METHODS: ACL reconstruction was carried out in a rat model in three randomly assigned groups: high-strain daily loading beginning on either (1) postoperative day one (immediate-loading group; n = 7) or (2) postoperative day four (delayed-loading group; n = 11) or (3) after prolonged immobilization (immobilized group; n = 8). Animals were killed two weeks after surgery and micro-computed tomography (micro-CT) and biomechanical testing of the bone-tendon-bone complex were carried out. RESULTS: The delayed-loading group had greater tissue mineral density than either the immediate-loading or immobilized group (mean [and standard deviation], 813.0 ± 24.9 mg/mL compared with 778.4 ± 32.6 mg/mL and 784.9 ± 26.4 mg/mL, respectively; p < 0.05). There was a trend toward greater bone volume per total volume fraction in both the immobilized and the delayed-loading group compared with the immediate-loading group (0.24 ± 0.03 and 0.23 ± 0.06 compared with 0.20 ± 0.05; p = 0.06). Trabecular thickness was greater in the immobilized group compared with the immediate-loading group (106.5 ± 23.0 µm compared with 72.6 ± 10.6 µm; p < 0.01). There were no significant differences in failure load or stiffness between the immobilized group and either high-strain cyclic-loading group. CONCLUSIONS: Immediate application of high-strain loading appears to have a detrimental effect on healing in this rat model. Any beneficial effects of delayed loading on the healing tendon-bone interface (after a brief period of immobilization) may be offset by the detrimental effects of excessive strain levels or by the detrimental effects of stress deprivation on the graft. CLINICAL RELEVANCE: The timing and magnitude of mechanical load on a healing rat ACL reconstruction graft may have important implications for postoperative rehabilitation. Avoidance of exercises that cause high graft strain in the early postoperative period may lead to improved tendon-to-bone healing in humans.

The effect of mechanical load on tendon-to-bone healing in a rat model.

BACKGROUND: Joint motion is commonly prescribed after tendon repair surgeries such as rotator cuff repairs; however, the ideal rehabilitation program to optimize tendon-to-bone healing is unknown. HYPOTHESES: (1) Delayed loading would result in a mechanically stronger and better organized tendon-to-bone interface compared with prolonged immobilization or immediate loading. (2) Low-magnitude load would lead to superior healing compared with high-magnitude load. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 192 rats underwent unilateral patellar tendon detachment and repair followed by placement of a custom external fixator. Rats were assigned to immobilization, immediate postoperative loading, or delayed-onset loading (4- or 10-day delay). Loading was controlled using a specially designed motorized device to apply constant strain until 3 N (low load) or 6 N (high load) of axial tensile force was reached through the healing bone-tendon complex for 50 cycles per day. Rats were sacrificed at 4, 10, 21, or 28 days postoperatively for histomorphometric, immunohistochemical, radiographic, molecular, and biomechanical analyses. RESULTS: The load to failure was significantly higher in the immobilized group compared with the immediate and delayed loading groups (P < .05). Compared with loaded specimens, the immobilized specimens had significantly less fibrocartilage (at 4, 10, and 28 days), significantly better collagen fiber organization (at 4, 10, and 21 days), decreased expression of matrix metalloproteinase-13 (at 10, 21, and 28 days), and significantly fewer apoptotic cells (at 21 and 28 days). Micro-computed tomographic analyses showed that the 3-N immediate load group had significantly less total volume (P = .012), bone volume (P = .012), and bone mineral density (P = .023) for cortical bone, and the immobilized group had significantly more specimens with new bone formation at the enthesis (100%; P = .001). CONCLUSION: Immobilization results in a stronger tendon-bone complex, with less scar tissue and a more organized tendon-bone interface compared with all loading regimens in this study. CLINICAL RELEVANCE: Given the relatively high rate of failure after rotator cuff and other tendon-to-bone repairs, identification of optimal rehabilitation programs postoperatively is an important research goal.

Fluoroquinolones impair tendon healing in a rat rotator cuff repair model: a preliminary study.

BACKGROUND: Recent studies suggest that fluoroquinolone antibiotics predispose tendons to tendinopathy and/or rupture. However, no investigations on the reparative capacity of tendons exposed to fluoroquinolones have been conducted. HYPOTHESIS: Fluoroquinolone-treated animals will have inferior biochemical, histological, and biomechanical properties at the healing tendon-bone enthesis compared with controls. STUDY DESIGN: Controlled laboratory study. METHODS: Ninety-two rats underwent rotator cuff repair and were randomly assigned to 1 of 4 groups: (1) preoperative (Preop), whereby animals received fleroxacin for 1 week preoperatively; (2) pre- and postoperative (Pre/Postop), whereby animals received fleroxacin for 1 week preoperatively and for 2 weeks postoperatively; (3) postoperative (Postop), whereby animals received fleroxacin for 2 weeks postoperatively; and (4) control, whereby animals received vehicle for 1 week preoperatively and for 2 weeks postoperatively. Rats were euthanized at 2 weeks postoperatively for biochemical, histological, and biomechanical analysis. All data were expressed as mean ± standard error of the mean (SEM). Statistical comparisons were performed using either 1-way or 2-way ANOVA, with P < .05 considered significant. RESULTS: Reverse transcriptase quantitative polymerase chain reaction (RTqPCR) analysis revealed a 30-fold increase in expression of matrix metalloproteinase (MMP)-3, a 7-fold increase in MMP-13, and a 4-fold increase in tissue inhibitor of metalloproteinases (TIMP)-1 in the Pre/Postop group compared with the other groups. The appearance of the healing enthesis in all treated animals was qualitatively different than that in controls. The tendons were friable and atrophic. All 3 treated groups showed significantly less fibrocartilage and poorly organized collagen at the healing enthesis compared with control animals. There was a significant difference in the mode of failure, with treated animals demonstrating an intrasubstance failure of the supraspinatus tendon during testing. In contrast, only 1 of 10 control samples failed within the tendon substance. The healing enthesis of the Pre/Postop group displayed significantly reduced ultimate load to failure compared with the Preop, Postop, and control groups. There was no significant difference in load to failure in the Preop group compared with the Postop group. Pre/Postop animals demonstrated significantly reduced cross-sectional area compared with the Postop and control groups. There was also a significant reduction in area between the Preop and control groups. CONCLUSION: In this preliminary study, fluoroquinolone treatment negatively influenced tendon healing. CLINICAL RELEVANCE: These findings indicate that there was an active but inadequate repair response that has potential clinical implications for patients who are exposed to fluoroquinolones before tendon repair surgery.

Allograft replacement for absent native tissue.

CONTEXT: Structural instability due to poor soft tissue quality often requires augmentation. Allografts are important biological substitutes that are used for the symptomatic patient in the reconstruction of deficient ligaments, tendons, menisci, and osteochondral defects. Interest in the clinical application of allografts has arisen from the demand to obtain stable anatomy with restoration of function and protection against additional injury, particularly for high-demand patients who participate in sports. Traditionally, allografts were employed to reinforce weakened tissue. However, they can also be employed to substitute deficient or functionally absent tissue, particularly in the sports medicine setting. OBJECTIVE: This article presents a series of 6 cases that utilized allografts to restore functionally deficient anatomic architecture, rather than just simply augmenting the degenerated or damaged native tissue. Detailed discussions are presented of the use of allografts as a successful treatment strategy to replace functionally weakened tissue, often after failed primary repairs.

The basic science of human knee menisci: structure, composition, and function.

CONTEXT: Information regarding the structure, composition, and function of the knee menisci has been scattered across multiple sources and fields. This review contains a concise, detailed description of the knee menisci-including anatomy, etymology, phylogeny, ultrastructure and biochemistry, vascular anatomy and neuroanatomy, biomechanical function, maturation and aging, and imaging modalities. EVIDENCE ACQUISITION: A literature search was performed by a review of PubMed and OVID articles published from 1858 to 2011. RESULTS: This study highlights the structural, compositional, and functional characteristics of the menisci, which may be relevant to clinical presentations, diagnosis, and surgical repairs. CONCLUSIONS: An understanding of the normal anatomy and biomechanics of the menisci is a necessary prerequisite to understanding the pathogenesis of disorders involving the knee.

Epidemiology of injuries and prevention strategies in competitive swimmers.

CONTEXT: Competitive swimmers are predisposed to musculoskeletal injuries of the upper limb, knee, and spine. This review discusses the epidemiology of these injuries, in addition to prevention strategies that may assist the physician in formulating rehabilitation programs for the swimmer following an injury. EVIDENCE ACQUISITION: A literature search was performed by a review of Google Scholar, OVID, and PubMed articles published from 1972 to 2011. RESULTS: This study highlights the epidemiology of injuries common to competitive swimmers and provides prevention strategies for the sports health professional. CONCLUSIONS: An understanding of swimming biomechanics and typical injuries in swimming aids in early recognition of injury, initiation of treatment, and design of optimal prevention and rehabilitation strategies.

Diabetes mellitus alters the mechanical properties of the native tendon in an experimental rat model.

The purpose of this study was to determine the effect of the diabetic phenotype on the mechanical properties of the native patellar tendon and its enthesis. Diabetes was induced via intraperitoneal injection of streptozotocin in Lewis rats. Control (n = 18) and diabetic animals (n = 20) were killed at 12 and 19 days for analysis. Statistical comparisons were performed using Student's t-tests and a two-tailed Fisher test with significance set at p < 0.05. Pre- and post-injection intraperitoneal glucose tolerance tests demonstrated significant impairment of glycemic control in the diabetic compared to control animals (p = 0.001). Mean serum hemoglobin A1c levels at 19 days was 10.6 ± 2.7% and 6.0 ± 1.0% for the diabetic and control groups, respectively (p = 0.0001). Fifteen of sixteen diabetic animals demonstrated intrasubstance failure of the patellar tendon, while only 7 of 14 control specimens failed within the tendon substance. The Young's modulus of the diabetic tendon was significantly lower than control specimens by 19 days post-induction (161 ± 10 N m(-2) compared to 200 ± 46 N m(-2) , respectively) (p = 0.02). The metabolic condition of poorly controlled diabetes negatively affects the mechanical properties of the native patellar tendon. These altered structural properties may predispose diabetic patients to a greater risk of tendinopathy and/or traumatic rupture.

Calcium-phosphate matrix with or without TGF-ß3 improves tendon-bone healing after rotator cuff repair.

BACKGROUND: Rotator cuff tendon heals by formation of an interposed zone of fibrovascular scar tissue. Recent studies demonstrate that transforming growth factor-beta 3 (TGF-ß(3)) is associated with tissue regeneration and "scarless" healing, in contrast to scar-mediated healing that occurs with TGF-ß(1). HYPOTHESIS: Delivery of TGF-ß(3) in an injectable calcium-phosphate matrix to the healing tendon-bone interface after rotator cuff repair will result in increased attachment strength secondary to improved bone formation and collagen organization and reduced scar formation of the healing enthesis. STUDY DESIGN: Controlled laboratory study. METHODS: Ninety-six male Sprague-Dawley rats underwent unilateral detachment of the supraspinatus tendon followed by acute repair using transosseous suture fixation. Animals were allocated into 1 of 3 groups: (1) repair alone (controls, n = 32), (2) repair augmented by application of an osteoconductive calcium-phosphate (Ca-P) matrix only (n = 32), or (3) repair augmented with Ca-P matrix + TGF-ß(3) (2.75 µg) at the tendon-bone interface (n = 32). Animals were euthanized at either 2 weeks or 4 weeks postoperatively. Biomechanical testing of the supraspinatus tendon-bone complex was performed at 2 and 4 weeks (n = 8 per group). Microcomputed tomography was utilized to quantitate bone microstructure at the repair site. The healing tendon-bone interface was evaluated with histomorphometry and immunohistochemical localization of collagen types I (COLI) and III (COLIII). Statistical analysis was performed using 2-way analysis of variance with significance set at P < .05. RESULTS: There was significantly greater load to failure of the Ca-P matrix + TGF-ß(3) group compared with matrix alone or untreated controls at 4 weeks postoperatively (P = .04). At 2 weeks, microcomputed tomography revealed a larger volume of newly formed bone present at the healing enthesis in both experimental groups compared with the control group. By 4 weeks, this newly formed, woven bone had matured into calcified, lamellar bone. Histomorphometric analysis demonstrated significantly greater fibrocartilage and increased collagen organization at the healing tendon-bone insertion site in both experimental groups compared with the control group at 2 weeks (P = .04). Over time, TGF-ß(3) delivery led to greater COLI expression compared with COLIII at the healing enthesis, indicating a more favorable COLI to COLIII ratio with administration of TGF-ß(3). CONCLUSION: Augmentation with an osteoconductive Ca-P matrix at the tendon-bone repair site is associated with new bone formation, increased fibrocartilage, and improved collagen organization at the healing tendon-bone interface in the early postoperative period after rotator cuff repair. The addition of TGF-ß(3) significantly improved strength of the repair at 4 weeks postoperatively and resulted in a more favorable COLI/COLIII ratio. CLINICAL RELEVANCE: The delivery of TGF-ß(3) with an injectable Ca-P matrix at the supraspinatus tendon footprint has promise to improve healing after soft tissue repair.

Effect of short-duration low-magnitude cyclic loading versus immobilization on tendon-bone healing after ACL reconstruction in a rat model.

BACKGROUND: Successful anterior cruciate ligament reconstruction with use of soft-tissue grafts requires healing between tendon and bone. Little is known about the effect of mechanical load on the cellular and molecular cascade of tendon-to-bone healing. Understanding these mechanical influences has critical implications for postoperative rehabilitation following anterior cruciate ligament reconstruction. The purpose of this study was to test the hypothesis that, compared with perioperative immobilization, short-duration low-magnitude cyclic axial loading would result in impaired tendon-to-bone healing after anterior cruciate ligament reconstruction in a rat model. METHODS: Fifty-two male Sprague-Dawley rats underwent anterior cruciate ligament reconstruction with use of a flexor digitorum longus autograft. The patellar tendon, capsule, and ligamentous structures were circumferentially released, and an external fixator parallel to the anterior cruciate ligament graft was placed across the knee. Mechanical loading, consisting of cyclic displacement of the femur and tibia constrained to axial translation parallel to the graft, was applied daily. The rats were randomly assigned to immobilization or daily loading, for fourteen or twenty-eight days. Biomechanical, micro-computed tomographic, and histomorphometric analysis was performed on the bone-tendon-bone complexes. RESULTS: The load measured across the knees during cyclic displacement increased over time (p < 0.05). Load-to-failure testing of the isolated femur-anterior cruciate ligament graft-tibia specimens revealed no significant differences between groups at two or four weeks. By two weeks postoperatively, a greater number of ED1+ inflammatory macrophages (phagocytic cells involved in the initial injury response) were seen at the tendon-bone interface after loading in the cyclically loaded group than in the immobilized group (p = 0.01). Compared with the baseline values, the number of trabeculae was significantly lower after loading for four weeks (p = 0.02). CONCLUSIONS: Short-duration low-magnitude cyclic axial loading of the anterior cruciate ligament graft in the postoperative period is not detrimental to the strength of the healing tendon-bone interface but appears to be associated with greater inflammation and less bone formation in the tunnel in this rat model.

Doxycycline-mediated inhibition of matrix metalloproteinases improves healing after rotator cuff repair.

BACKGROUND: Recent studies demonstrate a potentially critical role of matrix metalloproteinases (MMPs) and their inhibitors in the pathophysiology of rotator cuff tears. HYPOTHESIS: Doxycycline-mediated MMP inhibition after rotator cuff repair will improve tendon-to-bone healing. STUDY DESIGN: Controlled laboratory study. METHODS: Rats (n = 183) underwent acute detachment and repair of the supraspinatus tendon and the animals were divided into 4 groups: In controls (n = 66), the supraspinatus was repaired to its anatomical footprint. In experimental groups, an identical surgery was performed with doxycycline (130 mg/kg/d) administered orally at (1) preoperative day 1 (n = 66), (2) postoperative day (POD) 5 (n = 28), or (3) POD 14 (n = 23). Animals were sacrificed at 5 days, 8 days, 2 weeks, and 4 weeks. Tendon-bone interface was evaluated with histomorphometry. Enzyme-linked immunosorbent assay for local MMP-13 activity was performed at 8 days and 4 weeks. Biomechanical testing of the healing enthesis was performed at 8 days, 2 weeks, and 4 weeks. Serum doxycycline levels were measured at sacrifice. Statistical analysis was performed using unpaired t tests and 2-way analysis of variance (P < .05). RESULTS: Serum doxycycline levels were significantly higher in all treated groups compared with controls (1830 +/- 835 vs 3 +/- 3 ng/mL, respectively; P < .001). Doxycycline-treated animals demonstrated greater metachromasia and improved collagen organization at the healing enthesis at POD 5 (P < .06), POD 8 (P < .03), and 2 weeks (P < .04). The MMP-13 activity was significantly reduced in doxycycline-treated compared with control animals at POD 8 (6740 +/- 2770 vs 10400 +/- 2930 relative fluorescent units [RFU], respectively; P < .02) but not at 4 weeks (3600 +/- 3280 vs 4530 +/- 2720 RFU, respectively). The healing enthesis of animals started on doxycycline preoperatively or at POD 5 had an increased load to failure compared to controls at 2 weeks (13.6 +/- 1.8 and 13.2 +/- 1.94 N vs 9.1 +/- 2.5 N, respectively; P < .01). CONCLUSION/CLINICAL RELEVANCE: Modulation of MMP-13 activity after rotator cuff repair may offer a novel biological pathway to augment tendon-to-bone healing.