An Injectable Containing Morphine, Ropivacaine, Epinephrine, and Ketorolac Is Not Cytotoxic to Articular Cartilage Explants From Degenerative Knees.

PURPOSE: The purpose of this study was to determine the effects of a multidrug injectate containing morphine, ropivacaine, epinephrine, and ketorolac, commonly referred to as the "Orthococktail," on cartilage tissue viability and metabolic responses using an established in vitro model. METHODS: With institutional review board approval and informed patient consent, tissues normally discarded after total knee arthroplasty (TKA) were recovered. Full-thickness cartilage explants (n = 72, Outerbridge grade 1 to 3) were created and bisected. Paired explant halves were treated with either 1 mL Orthococktail or 1 mL of saline and cultured for 8 hours at 37°C, with 0.5 mL of the treatment being removed and replaced with tissue culture media every hour. Explants were cultured for 6 days, and media were changed and collected on days 3 and 6. After day 6, tissues were processed for cell viability, weighed, and processed for histologic grading. Outcome measures were compared for significant differences between treated and untreated samples. RESULTS: There were no significant differences in cartilage viability between control and Orthococktail-treated samples across a spectrum of cartilage pathologies. Orthococktail treatment consistently resulted in a significant decrease in the release of PGE2, MCP-1, MMP-7, and MMP-8 on day 3 of culture and PGE2, MMP-3, MMP-7, and MMP-8 on day 6 of culture, compared with saline controls. CONCLUSION: The results of the present study indicate that an Orthococktail injection composed of morphine, ropivacaine, epinephrine, and ketorolac is associated with a transient decrease in degradative and inflammatory mediators produced by more severely affected articular cartilage and may mitigate perioperative joint pain such that postoperative narcotic drug use could be reduced. CLINICAL RELEVANCE: The Orthococktail solution used in this study may be a safe intraoperative, intra-articular injection option for patients undergoing joint arthroplasty and other joint preservation surgical procedures.

Innovations in Peripheral Nerve Injury: Current Concepts and Emerging Techniques to Improve Recovery.

Despite the surgical advances in treatment of peripheral nerve injuries, consistent recovery of function is limited suggesting that a multimodal approach is required to optimize nerve regeneration. This approach should include advanced surgical repair techniques, as well as tissue engineering, cellular therapies, and application of local and systemic modulators of neuroregeneration. Further research is needed to advance these therapies from the laboratory to clinical practice, and to further understand how these treatments and techniques can act in concert to optimize functional nerve regeneration.

Biologic Joint Restoration: A Translational Research Success Story.

Treatment options that result in consistently successful outcomes for young and active patients with joint disorders are needed. This article summarizes two decades of rigorous research using a bedside-to-bench- to-bedside translational approach based on the One Health - One Medicine concept that culminated in successful clinical use of biologic joint restoration options for treatment of knee, hip, ankle, and shoulder problems in this growing patient population.

Pulsed electromagnetic fields promote repair of focal articular cartilage defects with engineered osteochondral constructs.

Articular cartilage injuries are a common source of joint pain and dysfunction. We hypothesized that pulsed electromagnetic fields (PEMFs) would improve growth and healing of tissue-engineered cartilage grafts in a direction-dependent manner. PEMF stimulation of engineered cartilage constructs was first evaluated in vitro using passaged adult canine chondrocytes embedded in an agarose hydrogel scaffold. PEMF coils oriented parallel to the articular surface induced superior repair stiffness compared to both perpendicular PEMF (p = .026) and control (p = .012). This was correlated with increased glycosaminoglycan deposition in both parallel and perpendicular PEMF orientations compared to control (p = .010 and .028, respectively). Following in vitro optimization, the potential clinical translation of PEMF was evaluated in a preliminary in vivo preclinical adult canine model. Engineered osteochondral constructs (∅ 6 mm × 6 mm thick, devitalized bone base) were cultured to maturity and implanted into focal defects created in the stifle (knee) joint. To assess expedited early repair, animals were assessed after a 3-month recovery period, with microfracture repairs serving as an additional clinical control. In vivo, PEMF led to a greater likelihood of normal chondrocyte (odds ratio [OR]: 2.5, p = .051) and proteoglycan (OR: 5.0, p = .013) histological scores in engineered constructs. Interestingly, engineered constructs outperformed microfracture in clinical scoring, regardless of PEMF treatment (p < .05). Overall, the studies provided evidence that PEMF stimulation enhanced engineered cartilage growth and repair, demonstrating a potential low-cost, low-risk, noninvasive treatment modality for expediting early cartilage repair.

Metabolic responses of meniscal tissue to focal collagenase degeneration.

Purpose: The objective of this study was to determine the responses of normal meniscus to collagenase activity. It was hypothesized that meniscal explants exposed to collagenase would significantly increase release of pro-inflammatory cytokines and degradative enzymes, in a dose-dependent manner, compared to control.Methods: Menisci were harvested from adult dogs (n = 6) euthanized for reasons unrelated to this study. Meniscal explants were created from the central portion of lateral and medial meniscus. Explants were injected with 100 µl collagenase at a concentration of 50 µg/ml, 5 µg/ml, or 0 µg/ml of collagenase. Explants were cultured for 12 days, and media were changed and collected every 3 days for biomarker analyses. Differences among collagenase concentrations were determined by a three factor ANOVA with adjustment for multiple comparisons, with pre-adjustment statistical significance set at p < 0.05.Results: When data from all explants were compared, the 50 µg group released significantly higher IL-6 and PGE2, and the 5 µg group released significantly higher levels of MMP-3 and CTX-II compared to the 0 µg group. Explants from the medial meniscus released significantly more MMP-1, MMP-2, MMP-3, and MMP-13 in response to stimulation with 5 µg/ml of collagenase compared to explants from the lateral meniscus.Discussion: The data from this study indicate that in response to localized degradative enzyme activity, the meniscus increases the release of pro-inflammatory and degradative biomarkers in a dose-dependent manner. Further, these data indicate potential differences in metabolic responses of lateral versus medial menisci to collagenase insult.

Use of a Hyperosmolar Saline Solution to Mitigate Proinflammatory and Degradative Responses of Articular Cartilage and Meniscus for Application to Arthroscopic Surgery.

PURPOSE: This study was designed to evaluate differences in proinflammatory and degradative mediator production and extracellular matrix degradation from osteoarthritic knee articular cartilage and meniscus explants treated with either hyperosmolar saline or isotonic saline. METHODS: 6 mm-diameter full-thickness explants were created from articular cartilage and menisci recovered after patients underwent knee surgery. One explant half was treated for 3 hours with hyperosmolar saline (600 mOsm/L) and the corresponding half with isotonic saline (300 mOsm/L). Explants were subsequently cultured for 3 days in tissue culture media. On day 3, media were collected for biomarker analyses. Results were normalized to tissue wet weight and analyzed statistically. RESULTS: Articular cartilage was collected from 10 patients (5 male, 5 female; mean age = 66.9 years) and menisci were collected from 8 patients (2 male, 6 female; mean age = 66 years). Articular cartilage media concentrations of monocyte chemoattractant protein-1 (P = .001) and interleukin (IL)-6 (P = .049) were significantly lower in explants treated with hyperosmolar saline. Meniscus media concentrations of prostaglandin E2 (P = .008), monocyte chemoattractant protein-1 (P = .011), IL-6 (P = .029), IL-8 (P = .012), matrix metalloproteinase-2 (P = .011), and glycosaminoglycan (P = .008) were significantly lower in explants treated with hyperosmolar saline. CONCLUSIONS: Treatment of cartilage and meniscus explants with hyperosmolar saline effectively mitigated key proinflammatory mediator production, as well as degradative mediator production and glycosaminoglycan loss from meniscus, with no detrimental effects noted compared to isotonic saline. CLINICAL RELEVANCE: These results suggest that hyperosmolar saline irrigation fluid may provide a safe alternative to standard isotonic saline irrigation fluid, and could mitigate untoward effects associated with inflammatory responses after standard-of-care knee arthroscopy.

Comparison of biologic scaffolds for augmentation of partial rotator cuff tears in a canine model.

BACKGROUND: This study was designed to test the hypothesis that biologic scaffold augmentation of articular-sided partial-thickness supraspinatus tendon tears would be associated with superior functional, imaging, biomechanical, and histologic properties compared with untreated tears in a preclinical canine model. METHODS: With Institutional Animal Care and Use Committee approval, dogs (n = 16) underwent half-thickness resection of the articular portion of the supraspinatus tendon (SST). Defects were treated by débridement (DB) (n = 8) or scaffold augmentation on the bursal side using amnion matrix cord scaffold (AM) (n = 8), decellularized human dermal allograft (AF) (n = 8), or bovine collagen patch (RMP) (n = 8). Control dogs (n = 4; 8 normal shoulders) were included. Assessments included lameness, function, comfortable shoulder range of motion (CROM), pain, ultrasonography, magnetic resonance imaging (MRI), arthroscopy, gross examination, biomechanical testing, and histopathology. RESULTS: At 3 months, CROM was significantly lower and pain significantly higher in DB compared with all other groups. At 6 months, CROM was significantly lower and pain significantly higher in RMP compared with AM and AF, and AM and AF showed significantly less thickening than DB and RMP. AF had the least severe MRI pathology and AM had significantly less MRI pathology than DB. AF SSTs and biceps tendons showed the least severe histopathology, and AM SSTs showed significantly less histopathology than DB and RMP SSTs. CONCLUSION: Biologic scaffolds can be effective in augmenting healing of articular-sided partial-thickness SST tears when compared with débridement in a preclinical canine model. Decellularized human dermal allograft and amnion matrix cord may have advantages over the bovine collagen patch for use in this indication.

Meniscal biology in health and disease.

The knee is a fascinating yet complex joint. Researchers and clinicians agree that the joint is an organ comprised of highly specialized intrinsic and extrinsic tissues contributing to both health and disease. Key to the function and movement of the knee are the menisci, exquisite fibrocartilage structures that are critical structures for maintaining biological and biomechanical integrity of the joint. The biological/physiological functions of the menisci must be understood at the tissue, cellular and even molecular levels in order to determine clinically relevant methods for assessing it and influencing it. By investigating normal and pathological functions at the basic science level, we can begin to translate data to patients. The objective of this article is to provide an overview of this translational pathway so that progression toward improved diagnostic, preventative, and therapeutic strategies can be effectively pursued. We have thoroughly examined the pathobiological, biomarker, and imaging aspects of meniscus research. This translational approach can be effective toward optimal diagnosis, prevention, and treatment for the millions of patients who suffer from meniscal disorders each year.

Biologic Joint Repair Strategies: The Mizzou BioJoint Story.

Because articular cartilage has very limited healing potential, most symptomatic cartilage injuries eventually result in end-stage osteoarthritis and are treated with artificial joint replacement. Our interdisciplinary, comparative orthopedic research performed by a team of DVMs, MDs, engineers, and basic scientists has yielded marked progress toward effective biologic joint restoration strategies by bringing bench-side ideas to fruition in bedside applications in both canine and human patients. This mini-review summarizes the progress of biologic joint restoration strategies at our center.

Effects on exposed articular cartilage during open surgical procedures: a comparison of various fluids in an animal model.

PURPOSE: The aim of this study was to assess the potential detrimental effects of the operating room environment on exposed healthy articular cartilage and to evaluate tissue hydration treatment strategies for preserving chondrocyte viability and extracellular matrix composition in this environment. METHODS: With institutional Animal Care and Use Committee approval, femoral and tibial condyles (n = 36; 6 per specimen) were harvested from canine cadavers (n = 6) immediately after euthanasia and placed on a draped operating table under standard surgical lighting for a timed 2-hour period. Each condyle was randomly assigned to one of 6 groups (n = 6 per group): no-treatment control, hyaluronic acid (HA), saline sponge, saline drip, culture media (Dulbecco's modified Eagle's medium [DMEM]) sponge, or culture media drip. Full-thickness cartilage sections were collected from each specimen immediately after harvest (time 0) and immediately after 2-hour exposure (time 2H), and processed to determine chondrocyte viability, tissue water content, and extracellular matrix composition (glycosaminoglycan [GAG] and collagen content). RESULTS: Chondrocyte viability was significantly lower (P = .03) after the 2-hour exposure in the control group. HA, saline sponge, and saline drip treatment groups all had significantly higher (P < .043) chondrocyte viability compared with controls at time 2H. Water content was significantly lower (P < .01) after the 2-hour exposure in the control group. Further, the water content in the control group was significantly lower than all treatment groups at time 2H (P < .001). No significant differences in tissue collagen or GAG content were observed within groups between time points or among groups at either time point. CONCLUSIONS: Canine articular cartilage did not demonstrate any reduction in chondrocyte viability or tissue water content at 2 hours when treated with hyaluronic acid, saline drip, saline-soaked sponge, or DMEM-soaked sponge compared with untreated exposed cartilage. CLINICAL RELEVANCE: Surgeons should consider the use of a hydrating solution for the treatment of exposed articular cartilage during open joint surgery of 2 hours or longer duration.

Hyperosmolar irrigation compared with a standard solution in a canine shoulder arthroscopy model.

BACKGROUND: A hyperosmolar irrigation solution may decrease fluid extravasation during arthroscopic procedures. Demonstrating the safety of a hyperosmolar irrigation solution with respect to chondrocyte viability and cartilage water content was deemed necessary before designing a clinical efficacy study. METHODS: We designed a translational animal model study in which hyperosmolar arthroscopy irrigation fluid (1.8%, 600 mOsm/L) was compared with normal saline (0.9%, 300 mOsm/L). Purpose-bred research dogs (n = 5) underwent bilateral shoulder arthroscopy. Irrigation fluid was delivered to each shoulder joint (n = 10) at 40 mm Hg for 120 minutes using standard ingress and egress portals. The percentage change in shoulder girth was documented at the completion of 120 minutes. Articular cartilage sections from the glenoid and humeral head were harvested from both shoulders. Chondrocyte viability and tissue water content were evaluated. Differences between groups and compared with time 0 controls were determined, with significance set at P <.05. RESULTS: The mean percentage change in shoulder girth was higher in the isotonic control group (13.3%) than in the hyperosmolar group (10.4%). Chondrocyte viability and tissue water content for glenoid and humeral head cartilage were well maintained in both treatment groups, and differences were not statistically significant. CONCLUSIONS: The data from this study suggest that doubling the osmolarity of the standard irrigation solution used for arthroscopy was not associated with any detrimental effects on chondrocyte viability or tissue water content after 2 hours of arthroscopic irrigation. On the basis of potential benefits in conjunction with the safety demonstrated in these data, clinical evaluation of a hyperosmolar solution for irrigation during shoulder arthroscopy appears warranted.

A novel system improves preservation of osteochondral allografts.

BACKGROUND: Osteochondral allografting is an option for successful treatment of large articular cartilage defects. Use of osteochondral allografting is limited by graft availability, often because of loss of chondrocyte viability during storage. QUESTIONS/PURPOSES: The purpose of this study was to compare osteochondral allografts implanted in canine knees after 28 days or 60 days of storage for (1) initial (1 week) safety and feasibility; (2) integrity and positioning with time (12 weeks and 6 months); and (3) gross, cell viability, histologic, biochemical, and biomechanical characteristics at an endpoint of 6 months. METHODS: With Institutional Animal Care and Use Committee approval, adult dogs (n=16) were implanted with 8-mm cylindrical osteochondral allografts in the lateral and medial femoral condyles of one knee. Osteochondral allografts preserved for 28 or 60 days using either the current tissue bank standard-of-care (SOC) or a novel system (The Missouri Osteochondral Allograft Preservation System, or MOPS) were used, creating four treatment groups: SOC 28-day, MOPS 28-day, SOC 60-day, and MOPS 60-day. Bacteriologic analysis of tissue culture and media were performed. Dogs were assessed by radiographs and arthroscopy at interim times and by gross, cell viability, histology, biochemistry, and biomechanical testing at the 6-month endpoint. RESULTS: With the numbers available, there was no difference in infection frequency during storage (5% for SOC and 3% for MOPS; p=0.5). No infected graft was implanted and no infections occurred in vivo. MOPS grafts had greater chondrocyte viability at Day 60 (90% versus 53%; p=0.002). For 60-day storage, MOPS grafts were as good as or better than SOC grafts with respect to all outcome measures assessed 6 months after implantation. CONCLUSIONS: Donor chondrocyte viability is important for osteochondral allograft success. MOPS allows preservation of chondrocyte viability for up to 60 days at sufficient levels to result in successful outcomes in a canine model of large femoral condylar articular defects. CLINICAL RELEVANCE: These findings provide a promising development in osteochondral allograft technology that can benefit the quantity of grafts available for use and the quality of grafts being implanted.

Cell-Mediated Immune Responses May Play Roles in Osteochondral Allograft Transplantation Osteointegration Failures.

Prolonged and incomplete osteochondral allograft (OCA) osteointegration is consistently cited as a major mechanism for OCA treatment failure. Subrejection immune responses may play roles in this mode of failure. Preimplantation OCA preparation techniques, including subchondral bone drilling, thorough irrigation, and autogenous bone marrow aspirate concentrate saturation, may dampen immune responses and improve OCA osteointegration. This study sought to further characterize potential immune system contributions to OCA transplantation treatment failures by analyzing donor-recipient ABO and Rh-factor mismatches and histological and immunohistochemical assessments of transplanted OCA tissues recovered from revision surgeries. Using a dedicated registry, OCA transplant recipients with documented treatment failures who met inclusion criteria (n = 33) as well as age-, body mass index-, and joint-matched patients with successful outcomes (n = 70) were analyzed to compare matched cohorts of patients with successful versus failed OCA transplantation outcomes. Tissues recovered from 18 failed OCA transplants and portions of 7 nonimplanted OCA controls were further analyzed to provide contributing evidence for potential immune response mechanisms. For patients analyzed, no statistically significant differences in proportions for treatment success versus failure based on mismatches for ABO type, Rh factor, or both were noted. Further, no statistically significant differences in proportions for histological immune response presence or absence based on mismatches for ABO type, Rh factor, or both were noted. Twelve (67%) of the failed OCA tissues contained lymphocyte aggregations in the subchondral bone, which were comprised of combinations of CD3 + , CD4 + , CD8 + , and CD20+ lymphocytes. The mechanisms of failure for these 12 OCA transplants involved insufficient OCA osteointegration. Results of this study suggest that T- and B-cell-mediated subrejection immune responses may play roles in OCA transplant treatment failures independent of donor-recipient blood type mismatch effects.

The osteoarthritis prevention study (TOPS) - A randomized controlled trial of diet and exercise to prevent Knee Osteoarthritis: Design and rationale.

Background: Osteoarthritis (OA), the leading cause of disability among adults, has no cure and is associated with significant comorbidities. The premise of this randomized clinical trial is that, in a population at risk, a 48-month program of dietary weight loss and exercise will result in less incident structural knee OA compared to control. Methods/design: The Osteoarthritis Prevention Study (TOPS) is a Phase III, assessor-blinded, 48-month, parallel 2 arm, multicenter randomized clinical trial designed to reduce the incidence of structural knee OA. The study objective is to assess the effects of a dietary weight loss, exercise, and weight-loss maintenance program in preventing the development of structural knee OA in females at risk for the disease. TOPS will recruit 1230 ambulatory, community dwelling females with obesity (Body Mass Index (BMI) â€‹≥ â€‹30 â€‹kg/m2) and aged ≥50 years with no radiographic (Kellgren-Lawrence grade ≤1) and no magnetic resonance imaging (MRI) evidence of OA in the eligible knee, with no or infrequent knee pain. Incident structural knee OA (defined as tibiofemoral and/or patellofemoral OA on MRI) assessed at 48-months from intervention initiation using the MRI Osteoarthritis Knee Score (MOAKS) is the primary outcome. Secondary outcomes include knee pain, 6-min walk distance, health-related quality of life, knee joint loading during gait, inflammatory biomarkers, and self-efficacy. Cost effectiveness and budgetary impact analyses will determine the value and affordability of this intervention. Discussion: This study will assess the efficacy and cost effectiveness of a dietary weight loss, exercise, and weight-loss maintenance program designed to reduce incident knee OA. Trial registration: ClinicalTrials.gov Identifier: NCT05946044.

Making the Case for Hyperosmolar Saline Arthroscopic Irrigation Fluids: A Systematic Review of Basic Science, Translational, and Clinical Evidence.

Commonly used isotonic arthroscopic irrigation fluids, such as normal saline or lactated Ringer's, were initially formulated for intravenous administration so they do not replicate the physiologic properties of healthy synovial fluid. Synovial fluid plays an important role in regulating joint homeostasis such that even transient disruptions in its composition and physiology can be detrimental. Previous studies suggest that hyperosmolar solutions may be a promising alternative to traditional isotonic fluids. This manuscript sought to systematically review and synthesize previously published basic science, translational, and clinical studies on the use of hyperosmolar arthroscopic irrigation fluids to delineate the optimal fluid for clinical use. A systematic literature search of MEDLINE/PubMed and Embase databases was performed in accordance with Preferred Reporting Items for Systemic Reviews and Meta-analyses (PRISMA) guidelines. The search phrases were: ("cartilage" AND "hyperosmolar"); ("arthroscopy" OR "arthroscopic" AND "hyperosmolar"). The titles, abstracts, and full texts were screened for studies on hyperosmolar solutions and articular cartilage. Study quality was assessed, and relevant data were collected. A meta-analysis was not performed due to study heterogeneity. A risk of bias assessment was performed on the included translational and clinical studies. There were 10 basic science studies, 2 studies performed in translational animal models, and 2 clinical studies included in this review. Of the basic science studies, 7 utilized a mechanical injury model. The translational studies were carried out in the canine shoulder and equine stifle (knee) joint. Clinical studies were performed in the shoulder and knee. Multiple basic science, translational, and clinical studies highlight the short-term safety, cost-effectiveness, and potential benefits associated with use of hyperosmolar solutions for arthroscopic irrigation. Further work is needed to develop and validate the ideal formulation for a hyperosmolar irrigation solution with proven long-term benefits for patients undergoing arthroscopic surgeries.

Evaluation of mechanistic serum and urine biomarkers for secondary osteoarthritis associated with developmental dysplasia of the hip.

Objective: Determine measurable differences for mechanistic urine and serum biomarkers in patients with developmental dysplasia of the hip (DDH) prior to, and following, secondary hip osteoarthritis (OA) when compared to controls. Design: Urine and serum were collected from individuals with developmental dysplasia of the hip (n = 39), prior to (Pre-OA DDH, n = 32) and following diagnosis of secondary hip OA (Post-OA DDH, n = 7), age-matched Pre-OA controls (n = 35), and age-matched Post-OA controls (n = 12). Samples were analyzed for protein biomarkers with potential for differentiation of hip status through a Mann-Whitney U test with a Benjamini-Hochberg correction. Results: Several interleukin and degradation related proteins were found to be differentially expressed when comparing DDH-related hip status prior to and following diagnosis of hip OA. In addition, MCP-1 and TIMP-1 were significantly different between younger and older patients in the control cohorts. Conclusion: These results provide initial evidence for serum and urine protein biomarkers that define clinically relevant stages of symptomatic DDH and its progression to secondary hip osteoarthritis categorized by known mechanisms of disease. Level of evidence: III.

Evaluation of Serum and Urine Biomarker Panels for Developmental Dysplasia of the Hip Prior to Onset of Secondary Osteoarthritis.

OBJECTIVE: Evaluate serum and urine biomarker panels for their capabilities in discriminating between individuals (13- to 34-years-olds) with healthy hips versus those with developmental dysplasia of the hip (DDH) prior to diagnosis of secondary hip osteoarthritis (OA). DESIGN: Urine and serum were collected from individuals (15-33 years old) with DDH, prior to and following diagnosis of hip OA, and from age-matched healthy-hip controls. Samples were analyzed for panels of protein biomarkers with potential for differentiation of hip status using receiver operator characteristic curve (area under curve [AUC]) assessments. RESULTS: Multiple urine and serum biomarker panels effectively differentiated individuals with DDH from healthy-hip controls in a population at risk for developing secondary hip OA with the best performing panel demonstrating an AUC of 0.959. The panel comprised of two serum and two urinary biomarkers provided the highest combined values for sensitivity, 0.85, and specificity, 1.00, while a panel of four serum biomarkers provided the highest sensitivity, 0.93, while maintaining adequate specificity, 0.71. CONCLUSION: Results of this study indicate that panels of protein biomarkers measured in urine and serum may be able to differentiate young adults with DDH from young adults with healthy hips. These data suggest the potential for clinical application of a routine diagnostic method for cost-effective and timely screening for DDH in at-risk populations. Further development and validation of these biomarker panels may result in highly sensitive and specific tools for early diagnosis, staging, and prognostication of DDH, as well as treatment decision making and monitoring capabilities. LEVEL OF EVIDENCE: III.

Improved preservation of fresh osteochondral allografts for clinical use.

INTRODUCTION: Fresh osteochondral allografts (OCAs) have been used clinically to treat cartilage focal defects of the knee for over 30 years. Over the last decade, significant research has been performed to develop and improve protocols for preservation of osteochondral tissue before transplantation into patients for treatment of cartilage defects. This work has resulted in preservation protocols that allow for maintenance of OCA tissues for time periods sufficient for clinical use based on disease testing requirements in the United States. However, graft quality and the window for clinical use of these tissues could be greatly enhanced from current levels. MATERIALS AND METHODS: Femoral condyles from 14 dogs were harvested and stored in one of the three proprietary media composition (M-1, M-2, M-3) and container condition (C-1, C-2, C-3) at 25 degrees C for 63 days. Viability of the OCA was determined using a proprietary media metabolic assay and live cell fluorescent microscopy. Media biomarker concentrations were analyzed to determine the metabolic activity of tissue. RESULTS: Media protein biomarkers were detected throughout the culture period, indicating OCAs remain metabolically active at 25 degrees C, and biomarker levels correlated with tissue viability. Viable chondrocyte density was maintained at day 0 levels throughout the depth of the tissue in the M-3 media using container condition C-3 after 63 days in storage. The media metabolic assay correlated strongly to cell viability of the OCA tissue. CONCLUSION: These data indicate that near day 0 tissue viability can be maintained for up to 63 days when OCAs are stored at 25 degrees C in the correct conditions. Further, tissue viability could be assessed nondestructively using media biomarkers and the media metabolic assay. If the preservation protocol reported here can be validated for safety and functional outcome, it could then be employed in tissue banks throughout the world, decreasing the number of grafts discarded and improving quality of life for thousands of patients affected by cartilage defects.

Small laboratory animal models of anterior cruciate ligament reconstruction.

Anterior cruciate ligament (ACL) injuries are common knee ligament injuries. While generally successful, ACL reconstruction that uses a tendon graft to stabilize the knee is still associated with a notable percentage of failures and long-term morbidities. Preclinical research that uses small laboratory species (i.e., mice, rats, and rabbits) to model ACL reconstruction are important to evaluate factors that can impact graft incorporation or posttraumatic osteoarthritis after ACL reconstruction. Small animal ACL reconstruction models are also used for proof-of-concept studies for the development of emerging biological strategies aimed at improving ACL reconstruction healing. The objective of this review is to provide an overview on the use of common small animal laboratory species to model ACL reconstruction. The review includes a discussion on comparative knee anatomy, technical considerations including types of tendon grafts employed amongst the small laboratory species (i.e., mice, rats, and rabbits), and common laboratory evaluative methods used to study healing and outcomes after ACL reconstruction in small laboratory animals. The review will also highlight common research questions addressed with small animal models of ACL reconstruction.

Acute Physiological Effects of Continuous Versus Intermittent Walking During Golf in Individuals With Knee Osteoarthritis: A Pilot Study.

OBJECTIVE: The aim of the study was to compare the acute effects of walking the golf course versus using a golf cart during a round of golf on biological markers of joint disease, joint pain, and cardiovascular parameters in individuals with knee osteoarthritis. METHODS: Participants with knee OA (n = 10) older than 50 yrs were recruited for this crossover designed study in which they completed two 18-hole rounds of golf: (1) walking the course and (2) using a golf cart. Five control participants (n = 5) performed the walking condition only. Step count, heart rate, rating of perceived exertion and pain using the Numeric Pain Rating Scale were measured during the round. Serum was collected at baseline, 9th hole (halfway), and 18th hole (completion) and tested for biomarkers associated with tissue turnover (cartilage oligomeric matrix protein), inflammation (tumor necrosis factor α, interleukin 1ß, interleukin 6), and degradative enzyme production (matrix metalloproteinase 3, matrix metalloproteinase 13). RESULTS: In knee OA participants, walking the course was associated with significantly higher step count and duration of moderate/vigorous physical activity (72.2% vs. 32.6% of the round) but did lead to a significant increase in knee joint pain (P < 0.05). Both conditions caused cartilage oligomeric matrix protein and matrix metalloproteinase 13 concentration increases from baseline to completion (P < 0.05), but inflammatory markers (tumor necrosis factor α, interleukin 6, and interleukin 1ß, P < 0.05) only increased when walking the course. Biomarker concentrations did not increase in control participants. CONCLUSIONS: Walking the course optimizes the duration of moderate/vigorous activity during a round of golf, but the golf cart is a beneficial option in those with exacerbated joint pain and inflammation that would otherwise limit participation.