A Bedside-to-Bench-to-Bedside Journey to Advance Osteochondral Allograft Transplantation towards Biologic Joint Restoration.

More than 70 million adults in the United States are impacted by osteoarthritis (OA). Symptomatic articular cartilage loss that progresses to debilitating OA is being diagnosed more frequently and earlier in life, such that a growing number of active patients are faced with life-altering health care decisions at increasingly younger ages. Joint replacement surgeries, in the form of various artificial arthroplasties, are reliable operations, especially for older (≥65 years), more sedentary patients with end-stage OA, but have major limitations for younger, more active patients.

Bacteriophage Therapy for Acute Fracture-Related Infections: An Effective Treatment When Compared to Antibiotics In A Canine Model.

Introduction: Acute fracture-related infections are challenging problems, affecting up to 20% of orthopaedic trauma patients. High recurrence rates, secondary surgeries, and rehospitalizations lead to increased healthcare costs and are major burdens to patients. Bacteriophage therapy offers a potential alternative treatment option to address these challenges.

Evaluation of Dexamethasone-Eluting Cell-Seeded Constructs in a Preclinical Canine Model of Cartilage Repair.

In this 12-month long, preclinical large animal study using a canine model, we report that engineered osteochondral grafts (comprised of allogeneic chondrocyte-seeded hydrogels with the capacity for sustained release of the corticosteroid dexamethasone [DEX], cultured to functional mechanical properties, and incorporated over porous titanium bases), can successfully repair damaged cartilage. DEX release from within engineered cartilage was hypothesized to improve initial cartilage repair by modulating the local inflammatory environment, which was also associated with suppressed degenerative changes exhibited by menisci and synovium. We note that not all histological and clinical outcomes at an intermediary time point of three months paralleled 12-month outcomes, which emphasizes the importance of studies in valid preclinical models that incorporate clinically relevant follow-up durations.

Development and validation of a preclinical canine model for early onset fracture-related infections.

Fracture-related infections (FRIs) are a challenging complication in orthopaedics. Standard of care management for FRIs typically involves prolonged antibiotic therapies, irrigation and debridement (I&D) of the fracture site, and retention of fracture-fixation implants with or without exchange. Unfortunately, this treatment regimen is associated with treatment failure rates of up to 38 %, such that improved preventive and therapeutic interventions are needed.

A preclinical model for osteoarticular fracture fragment preservation for delayed re-implantation.

Background: Open articular fractures often include contaminated, devascularized osteoarticular fragments that are critical for joint reconstruction. Definitive treatment is often delayed such that decontamination and preservation of critical fragments for joint reconstruction is highly desirable. To validate decontamination and preservation protocols for safe and effective preservation of osteoarticular fragments for re-implantation, a preclinical animal model for inducing type 3 open articular fractures with contaminated, devascularized osteoarticular fragments was developed and validated.

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.

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 test with a Benjamini-Hochberg correction.

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.

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.

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.

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.

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.

Tibial Bone Quality in Former Bariatric Surgery Patients with Osteoarthritis.

Unlabelled: 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.

Canine models of spine disorders.

Neck and low back pain are common among the adult human population and impose large social and economic burdens on health care and quality of life. Spine-related disorders are also significant health concerns for canine companions with etiopathogeneses, clinical presentations, and diagnostic and therapeutic options that are very similar to their human counterparts. Historically, induced and spontaneous pathology in laboratory rodents, dogs, sheep, goats, pigs, and nonhuman primates have been used for study of human spine disorders.

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.

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 = .

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.

Clinical Application of the Basic Science of Articular Cartilage Pathology and Treatment.

The joint is an organ with each tissue playing critical roles in health and disease. Intact articular cartilage is an exquisite tissue that withstands incredible biologic and biomechanical demands in allowing movement and function, which is why hyaline cartilage must be maintained within a very narrow range of biochemical composition and morphologic architecture to meet demands while maintaining health and integrity. Unfortunately, insult, injury, and/or aging can initiate a cascade of events that result in erosion, degradation, and loss of articular cartilage such that joint pain and dysfunction ensue.

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.

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).

Enhanced Subchondroplasty Treatment for Post-Traumatic Cartilage and Subchondral Bone Marrow Lesions in a Canine Model.

This study characterizes outcomes associated with subchondroplasty (SCP) versus SCP enhanced with platelet-rich plasma (PRP) or bone marrow aspirate concentrate (BMC) treatment of impact-induced subchondral bone marrow lesions (BML) using a validated preclinical canine model. With IACUC approval, purpose-bred research hounds (n = 24) underwent arthroscopic impact injury (40 N) to both medial femoral condyles. At 3 months, functional assessments, arthroscopy, and magnetic resonance imaging (MRI) were performed.

Metabolic responses of meniscal tissue to focal collagenase degeneration.

: 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.: Menisci were harvested from adult dogs (n = 6) euthanized for reasons unrelated to this study.