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.

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.

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.

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.

Suspensory Versus Interference Screw Fixation for Arthroscopic Anterior Cruciate Ligament Reconstruction in a Translational Large-Animal Model.

PURPOSE: To compare all-inside cortical-button suspensory fixation in sockets versus interference screw fixation in tunnels with respect to clinical, histologic, and biomechanical assessments of all-soft tissue (AST) tendon autografts used for anterior cruciate ligament (ACL) reconstruction in a canine model. METHODS: By use of a validated "hybrid" double-bundle ACL reconstruction technique (reconstruction of the anteromedial bundle with preservation of the native posterolateral bundle), dogs were randomly assigned to undergo either suspensory fixation in sockets (n = 6) or interference screw fixation in tunnels (n = 6). Contralateral knees were used as nonoperated controls (n = 12). Quadrupled extensor tendon autografts were used for both ACL reconstruction groups. Dogs were assessed radiographically and functionally and humanely euthanized at 12 weeks after surgery for arthroscopic, gross, biomechanical, and histologic assessments. RESULTS: Histologic assessments showed significantly (P = .018) better graft incorporation with 4-zone direct healing to bone for the grafts using suspensory fixation in sockets (16.3 ± 1.5) compared with the grafts using interference screw fixation in tunnels (14.2 ± 2.1). Furthermore, graft healing to bone was significantly better at the aperture (P = .05) and mid-socket (P = .01) location for the group that underwent suspensory fixation in sockets (16.1 ± 1.8 and 16.4 ± 1.9, respectively). CONCLUSIONS: Suspensory fixation of AST grafts in sockets was associated with superior tendon-to-bone healing compared with interference screw fixation in tunnels, with 4-zone direct graft healing to bone seen for femoral and tibial sockets only in the suspensory-fixation group. Biomechanical properties were similar between groups. CLINICAL RELEVANCE: These data provide evidence suggesting that an all-inside ACL reconstruction technique using adjustable-loop cortical-button suspensory fixation in bone sockets has potential clinical advantages for ACL reconstruction using AST grafts.

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.

Comparison of reamer irrigator aspirator (RIA) suspension versus bone marrow aspirate concentrate (BMC) for percutaneous treatment of long bone nonunions-A preclinical canine model.

OBJECTIVE: To compare the bone healing effects of percutaneously delivered bone marrow aspirate concentrate (BMC) versus reamer irrigator aspirator (RIA) suspension in a validated preclinical canine ulnar nonunion model. We hypothesized that BMC would be superior to RIA in inducing bone formation across a nonunion site after percutaneous application. The null hypothesis was that BMC and RIA would be equivalent. METHODS: A bilateral ulnar nonunion model (n= 6; 3 matched pairs) was created. Eight weeks after segmental ulnar ostectomy, RIA from the ipsilateral femur and BMC from the proximal humerus were harvested and percutaneously administered into either the left or right ulnar defect. The same volume (3 ml) of RIA suspension and BMC were applied on each side. Eight weeks after treatment, the dogs were euthanized, and the nonunions were evaluated using radiographic, biomechanical, and histologic assessments. RESULTS: All dogs survived for the intended study duration, formed radiographic nonunions 8 weeks after segmental ulnar ostectomy, and underwent the assigned percutaneous treatment. Radiographic and macroscopic assessments of bone healing at the defect sites revealed superior bridging-callous formation in BMC-treated nonunions. Histologic analyses revealed greater amount of bony bridging and callous formation in the BMC group. Biomechanical testing of the treated nonunions did not reveal any significant differences. CONCLUSION: Bone marrow aspirate concentrate (BMC) had important advantages over Reamer Irrigator Aspirator (RIA) suspension for percutaneous augmentation of bone healing in a validated preclinical canine ulnar nonunion model based on clinically relevant radiographic and histologic measures of bone formation.

Oral administration of an extended-release formulation of nitrofurantoin results in high concentrations in the urine of dogs.

OBJECTIVE: Sporadic bacterial cystitis in both dogs and humans is often caused by Escherichia coli. In humans, nitrofurantoin is a first-line antimicrobial for the treatment of bacterial cystitis but in dogs a lack of available data may be part of the reason it is only recommended as a second-line treatment. The objective of this preliminary study was to determine the plasma pharmacokinetics and urine concentrations of nitrofurantoin monohydrate-macrocrystalline in dogs. ANIMALS: 8 healthy female hound dogs. PROCEDURES: From July 26 to July 28, 2021, dogs received a single oral dose of nitrofurantoin monohydrate-macrocrystalline 100 mg with food. Blood and urine were collected at predetermined times. Nitrofurantoin concentrations were assayed by UPLC-MS/MS and plasma data were analyzed using noncompartmental methods. RESULTS: Plasma concentrations were low for all dogs with a mean ± SD maximum concentration (Cmax) of 0.242 ± 0.098 µg/mL (range, 0.14 to 0.42 µg/mL) occurring between 2 and 24 hours. Urine concentrations were manyfold higher than for plasma. Cmax in urine was 134 ± 54 µg/mL (range, 49.1 to 218 µg/mL) occurring between 6 and 36 hours. As seen in other species, nitrofurantoin concentrated in urine with concentrations being 500 times higher than the concentration in plasma. CLINICAL RELEVANCE: Results suggested that nitrofurantoin monohydrate-macrocrystalline formulation of nitrofurantoin should be effective in treating bacterial cystitis caused by susceptible uropathogens.

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.

Bilateral iliac arterial thrombosis in an alpaca (Vicugna pacos) cria.

A 3-month-old male alpaca was presented for acute onset of non-weight-bearing left hind limb lameness. Antemortem diagnostics revealed a mass to the right of the urinary bladder and no blood flow in the left femoral artery. Necropsy revealed bilateral iliac arterial thrombi and an abscess near the urinary bladder.A 3-month-old male alpaca was presented for acute onset of non-weight-bearing left hind limb lameness. Antemortem diagnostics revealed a mass to the right of the urinary bladder and no blood flow in the left femoral artery. Necropsy revealed bilateral iliac arterial thrombi and an abscess near the urinary bladder.

RésuméThrombose artérielle iliaque bilatérale chez un petit alpaga(Vicugna pacos) . Un alpaga mâle âgé de 3 mois a été présenté pour l'apparition aiguë d'une boiterie du membre postérieur gauche sans appui de poids. Les tests diagnostiques avant le décès ont révélé une masse à la droite de la vessie et l'absence de débit sanguin dans l'artère fémorale gauche. La nécropsie a révélé des thrombi artérielles iliaques bilatérales et un abcès près de la vessie.(Traduit par Isabelle Vallières).

Development and Assessment of Novel Multiligament Knee Injury Reconstruction Graft Constructs and Techniques.

Multiligament knee injury (MLKI) typically requires surgical reconstruction to achieve the optimal outcomes for patients. Revision and failure rates after surgical reconstruction for MLKI can be as high as 40%, suggesting the need for improvements in graft constructs and implantation techniques. This study assessed novel graft constructs and surgical implantation and fixation techniques for anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), posterior medial corner (PMC), and posterior lateral corner (PLC) reconstruction. Study objectives were (1) to describe each construct and technique in detail, and (2) to optimize MLKI reconstruction surgical techniques using these constructs so as to consistently implant grafts in correct anatomical locations while preserving bone stock and minimizing overlap. Cadaveric knees (n = 3) were instrumented to perform arthroscopic-assisted and open surgical creation of sockets and tunnels for all components of MLKI reconstruction using our novel techniques. Sockets and tunnels with potential for overlap were identified and assessed to measure the minimum distances between them using gross, computed tomographic, and finite element analysis-based measurements. Percentage of bone volume spared for each knee was also calculated. Femoral PLC-lateral collateral ligament and femoral PMC sockets, as well as tibial PCL and tibial PMC posterior oblique ligament sockets, were at high risk for overlap. Femoral ACL and femoral PLC lateral collateral ligament sockets and tibial popliteal tendon and tibial posterior oblique ligament sockets were at moderate risk for overlap. However, with careful planning based on awareness of at-risk MLKI graft combinations in conjunction with protection of the socket/tunnel and trajectory adjustment using fluoroscopic guidance, the novel constructs and techniques allow for consistent surgical reconstruction of all major ligaments in MLKIs such that socket and tunnel overlap can be consistently avoided. As such, the potential advantages of the constructs, including improved graft-to-bone integration, capabilities for sequential tensioning of the graft, and bone sparing effects, can be implemented.

Treatment-Monitoring Capabilities of Serum and Urine Biomarkers for Meniscal Allograft Transplantation in a Preclinical Canine Model.

BACKGROUND: Meniscal allograft transplantation (MAT) has been developed as a treatment for meniscal deficiency. Despite promising outcomes, there are no real-time methods to evaluate graft survivorship and predict functional outcomes. HYPOTHESIS: Assessment of serum and urine biomarkers could be used to develop biomarker panels-prognostic (1- and 3-month postsurgical time points) and diagnostic (6-month time point)-based on strong associations with clinically relevant outcome metrics obtained 6 months after surgery. STUDY DESIGN: Descriptive laboratory study. METHODS: Twelve adult purpose-bred research hounds were included and underwent medial meniscal release to induce meniscal deficiency. Three months after meniscal release surgery, medial menisci were replaced with fresh-frozen meniscus (n = 4), fresh meniscus (n = 4), or fresh meniscotibial osteochondral allograft (n = 4) such that a spectrum of pain and functional outcomes could be anticipated. Serum and urine from all dogs were collected preoperatively and at 1, 3, and 6 months after MAT surgery. Dogs were assessed for pain-related and functional outcomes at the same time points. To develop a prognostic panel of biomarkers, biomarker data from the 1- and 3-month post-MAT surgery time points were used to model 6-month clinical outcomes. A diagnostic panel of biomarkers was developed using data from the 6-month post-MAT surgery to model 6-month clinical outcomes. Primary outcomes for pain and function were visual analog scale (VAS) and operated limb percentage total pressure index (%TPI), respectively. Using random subject effects, linear mixed models were used to develop prognostic biomarker panels, and linear fixed-effect models were used to develop diagnostic biomarker panels, with variance explained for each panel reported (R2) along with individual biomarker relationships. RESULTS: Across prognostic biomarker panels, a panel including serum IL-6, IL-8, IL-10, and IL-18 was fit for the primary functional outcome, operated limb %TPI (R2 = 0.450), whereas a panel including serum CTX-II and OPG was fit for the primary pain-related outcome, VAS (R2 = 0.516). Across diagnostic biomarker panels, a panel including serum MMP-1 and MMP-3 and urine PINP and TIMP-1 was fit for %TPI (R2 = 0.863). Separately, a panel including urine CTX-I, CTX-II, IL-8, MMP-2, and TIMP-1 was fit as diagnostic biomarkers for the VAS for pain (R2 = 0.438). CONCLUSION: Biomarker panels of selected serum and/or urine proteins can model clinically relevant metrics for function and pain in a preclinical model of MAT. CLINICAL RELEVANCE: Biomarker panels could be used to provide real-time diagnostic and prognostic data regarding outcomes after MAT.

Does Irrigating While Drilling Decrease Bone Damage?

Background: Heat generated during bone drilling may be associated with thermal necrosis and direct damage, leading to complications after surgery. This preclinical study evaluates the in vivo effects of saline irrigation, drilling device type, and device sharpness on heat generation and bone damage in viable cortical bone. Methods: Bicortical drilling of each tibial diaphysis from anesthetized research dogs was performed to evaluate temperature and bone damage using five different devices with or without saline irrigation. Results: Saline irrigation and sharp drill bits were associated with smaller temperature increases and less acute osteonecrosis. Conventional trocar tip Kirschner wires were associated with the largest temperature increase and the most acute osteonecrosis changes. Conclusion: The use of saline irrigation during bone drilling reduces temperature change and osteonecrosis. Furthermore, we recommend that the use of dull drill bits or standard tip Kirschner wires be avoided. Lastly, drill bit design can directly contribute to bone damage during drilling. Clinical Relevance: This study provides in vivo data from a preclinical model to validate the benefits of saline irrigation and sharp drill bits during bone drilling to regulate increases in temperature and decrease associated osteonecrosis. Risk for early implant loosening and poor surgical outcome is influenced by thermal osteonecrosis of bone such that consistent use of saline irrigation, sharp drill bits, and optimized designs may have important clinical advantages. Level of Evidence: II.

Characterizing correlations among disease severity measures in osteochondral tissues from osteoarthritic knees.

Osteoarthritis (OA) is a complex disease with biologic, biomechanical, and clinical heterogeneity among patients. Relationships among OA tissue metabolism, histopathology, and extracellular matrix (ECM) composition have not been well characterized. It was hypothesized that moderate (r = .4-.69) to strong (r > .7) correlations exist among these different measures of disease severity in osteochondral tissues from OA knees. Joint surfaces were obtained from patients (n = 6) undergoing total knee arthroplasty. Osteochondral explants (n = 136) were created and cultured for 3 days. Culture media were collected for biomarker analyses, and tissue was assessed for viability, histological scoring, and ECM composition. Correlations among media biomarker concentrations, histological scoring, ECM composition, and viability were determined using a Spearman correlation. GRO-α, IL-6, IL-8, and MCP-1 showed strong positive correlations to each other, and moderate positive correlations to NO, PGE2, and MMP-2. Total MMP activity, MMP-9, and MMP-13 had strong positive correlations to each other, and moderate positive correlations to MMP-1. MMP-2 had a moderate to strong positive correlations to histological scores (total and cartilage structure) and collagen content. MMP-2, IL-6, IL-8, and MCP-1 had moderate negative correlations, and MMP-9 had a moderate positive correlation, to viability. GRO-α, IL-6, IL-8, and MCP-1 had moderate positive correlations to collagen content. MMP-9, MMP-13, and total MMP activity had moderate negative correlations to tissue GAG. The data suggest links among proinflammatory and degradative pathways are present in OA osteochondral tissues. Further characterization of these links have the potential to delineate mechanisms of disease and diagnostic and therapeutic targets for knee OA.

Tibial Bone Quality in Former Bariatric Surgery Patients with Osteoarthritis.

Downstream effects of bariatric weight-loss surgery have been associated with bone resorption, potentially jeopardizing total knee arthroplasty (TKA) implant fixation/ingrowth. PURPOSE: This case-control study sought to determine if TKA patients with history of bariatric surgery exhibit altered microanatomy of subchondral bone quality in the tibial plateau compared to controls. MATERIALS AND METHODS: With IRB approval, 41 bone samples were evaluated from 12 former bariatric surgery patients and 10 sex-, age-, weight-, height-, and BMI-matched controls. Patient-Reported Outcomes Measurement Information System (PROMIS) surveys were completed prior to TKA. Tibial plateau osteochondral tissues were recovered during the TKA procedure, and samples from the medial and lateral plateaus were dissected into 1 × 2 cm sections, scanned using microcomputed tomography (µCT), and plastic-embedded for histologic sectioning/staining of undecalcified bone. Paired t tests with Bonferroni correction were performed to assess group differences. RESULTS: Female bariatric surgery patients had reduced osteoid/total area and greater osteoclast number asymmetry than female controls (p < 0.03). No differences were noted in µCT or histologic bone parameters between bariatric and control patients when the sexes were combined. Bariatric patients self-reported worse preoperative PROMIS pain interference and physical function scores than controls (p < 0.04). CONCLUSIONS: Similarities of subchondral bone between former bariatric surgery patients and matched controls indicate OA disease progression dominates the bone landscape in both patient groups.

Unicompartmental bipolar osteochondral and meniscal allograft transplantation is effective for treatment of medial compartment gonarthrosis in a canine model.

Osteochondral allograft (OCA) transplantation can restore large articular defects in the knee. Bipolar OCA transplantations for partial and whole joint resurfacing often have less favorable results than single-surface transplants. This study was designed to use a large animal model to test the hypothesis that unicompartmental bipolar osteochondral and meniscal allograft transplantation (BioJoint) would be as or more effective for treatment of medial compartment osteoarthritis (OA) compared to standard-of-care nonoperative treatment. OA was induced in one knee of each research hound (n = 8) using a meniscal release model and pretreatment assessments were performed. After 3 months, dogs were randomly assigned to either the control group (n = 4, no surgical intervention, daily nonsteroidal antiinflammatory drugs [NSAIDs]) or the BioJoint group (n = 4). Clinical, radiographic, and arthroscopic assessments were performed longitudinally and histopathology was evaluated at the 6-month endpoint. At study endpoint, functional, pain, and total pressure index measures, as well as radiographic and arthroscopic grading of graft appearance and joint health, demonstrated superior outcomes for BioJoints compared to NSAID controls. Furthermore, histologic assessments showed that osteochondral and meniscal transplants maintain integrity and integrated into host tissues. Clinical significance: The results support the safety and efficacy of unicompartmental bipolar osteochondral and meniscal allograft transplantation in a preclinical model with highly functional outcomes without early OA progression.

Comparison of meniscal allograft transplantation techniques using a preclinical canine model.

Meniscal allograft transplantation (MAT) can be a safe, effective treatment for meniscal deficiency resulting in knee dysfunction, leading to osteoarthritis (OA) without proper treatment with 5-year functional success rates (75%-90%). While different grafts and techniques have generally proven safe and effective, complications include shrinkage, extrusion, progression of joint pathology, and failure. The objective of this study was to assess the functional outcomes after MAT using three different clinically-relevant methods in a preclinical canine model. The study was designed to test the hypothesis that fresh meniscal-osteochondral allograft transplantation would be associated with significantly better function and joint health compared with fresh-viable or fresh-frozen meniscus-only allograft transplantations. Three months after meniscal release to induce meniscus-deficient medial compartment disease, research hounds (n = 12) underwent MAT using meniscus allografts harvested from matched dogs. Three MAT conditions (n = 4 each) were compared: frozen meniscus-fresh-frozen meniscal allograft with menisco-capsular suture repair; fresh meniscus-fresh viable meniscal allograft (Missouri Osteochondral Preservation System (MOPS)-preservation for 30 days) with menisco-tibial ligament repair; fresh menisco-tibial-fresh, viable meniscal-tibial-osteochondral allografts (MOPS-preservation for 30 days) with menisco-tibial ligament preservation and autogenous bone marrow aspirate concentrate on OCA bone. Assessment was performed up to 6 months after MAT. Pain, comfortable range of motion, imaging, and arthroscopic scores as well histological and cell viability findings were superior (P < .05) for the fresh menisco-tibial group compared with the two other groups. Novel meniscal preservation and implantation techniques with fresh, MOPS-preserved, viable meniscal-osteochondral allografts with menisco-tibial ligament preservation appears to be safe and effective for restoring knee function and joint health in this preclinical model. This has the potential to significantly improve outcomes after MAT.