Local delivery of TGF-β1-mRNA decreases fibrosis in osteochondral defects.

Osteoarthritis (OA) is a condition that affects the quality of life of millions of patients worldwide. Current clinical treatments, in most cases, lead to cartilage repair with deposition of fibrocartilage tissue, which is mechanically inferior and not as durable as hyaline cartilage tissue. We designed an mRNA delivery strategy to enhance the natural healing potential of autologous bone marrow aspirate concentrate (BMAC) for articular cartilage repair.

A bioactive supramolecular and covalent polymer scaffold for cartilage repair in a sheep model.

Regeneration of hyaline cartilage in human-sized joints remains a clinical challenge, and it is a critical unmet need that would contribute to longer healthspans. Injectable scaffolds for cartilage repair that integrate both bioactivity and sufficiently robust physical properties to withstand joint stresses offer a promising strategy. We report here on a hybrid biomaterial that combines a bioactive peptide amphiphile supramolecular polymer that specifically binds the chondrogenic cytokine transforming growth factor β-1 (TGFβ-1) and crosslinked hyaluronic acid microgels that drive formation of filament bundles, a hierarchical motif common in natural musculoskeletal tissues.

Improving the Selectivity of an Osseointegrated Neural Interface: Proof of Concept For Housing Sieve Electrode Arrays in the Medullary Canal of Long Bones.

Sieve electrodes stand poised to deliver the selectivity required for driving advanced prosthetics but are considered inherently invasive and lack the stability required for a chronic solution. This proof of concept experiment investigates the potential for the housing and engagement of a sieve electrode within the medullary canal as part of an osseointegrated neural interface (ONI) for greater selectivity toward improving prosthetic control. are that (A) the addition of a sieve interface to a cuff electrode housed within the medullary canal of the femur as part of an ONI would be capable of measuring efferent and afferent compound nerve action potentials (CNAPs) through a greater number of channels; (B) that signaling improves over time; and (C) that stimulation at this interface generates measurable cortical somatosensory evoked potentials through a greater number of channels.

Experimental Basis for Creating an Osseointegrated Neural Interface for Prosthetic Control: A Pilot Study in Rabbits.

Introduction: While debate persists over how to best prevent or treat amputation neuromas, the more pressing question of how to best marry residual nerves to state-of-the-art robotic prostheses for naturalistic control of a replacement limb has come to the fore. One potential solution involves the transposition of terminal nerve ends into the medullary canal of long bones, creating the neural interface within the bone. Nerve transposition into bone is a long-practiced, clinically relevant treatment for painful neuromas.

Methodology for creating a chronic osseointegrated neural interface for prosthetic control in rabbits.

Background: Chronic stability and high degrees of selectivity are both essential but somewhat juxtaposed components for creating an implantable bi-directional PNI capable of controlling of a prosthetic limb. While the more invasive implantable electrode arrays provide greater specificity, they are less stable over time due to compliance mismatch with the dynamic soft tissue environment in which the interface is created.

New Method: This paper takes the surgical approach of transposing nerves into bone to create neural interface within the medullary canal of long bones, an osseointegrated neural interface, to provide greater stability for implantable electrodes.

Temporal mechanically-induced signaling events in bone and dorsal root ganglion neurons after in vivo bone loading.

Mechanical signals play an integral role in the regulation of bone mass and functional adaptation to bone loading. The osteocyte has long been considered the principle mechanosensory cell type in bone, although recent evidence suggests the sensory nervous system may play a role in mechanosensing. The specific signaling pathways responsible for functional adaptation of the skeleton through modeling and remodeling are not clearly defined.

Multiscale Porosity Directs Bone Regeneration in Biphasic Calcium Phosphate Scaffolds.

Large and load-bearing bone defects are challenging to treat and cause pain and disfigurement. The design of efficacious bone scaffolds for the repair of such defects involves a range of length scales from the centimeter down to the micrometer-scale. Here, we assess the influence on bone regeneration of scaffold rod spacing (>300 μm) and microporosity (<50 μm), as well as the combination of different structures and materials in the same scaffold, i.

Nanostructured Mineral Coatings Stabilize Proteins for Therapeutic Delivery.

Proteins tend to lose their biological activity due to their fragile structural conformation during formulation, storage, and delivery. Thus, the inability to stabilize proteins in controlled-release systems represents a major obstacle in drug delivery. Here, a bone mineral inspired protein stabilization strategy is presented, which uses nanostructured mineral coatings on medical devices.

In vitro biomechanical evaluation of four surgical techniques for fusion of equine centrodistal and tarsometatarsal joints.

OBJECTIVE To evaluate the biomechanical properties of 4 methods for fusion of the centrodistal and tarsometatarsal joints in horses and compare them among each other and with control tarsi. SAMPLE 24 sets of paired tarsi without substantial signs of osteoarthritis harvested from equine cadavers. PROCEDURES Test constructs (n = 6/type) were prepared from 1 tarsus from each pair to represent surgical drilling; 2 medially to laterally placed kerf-cut cylinders (MLKCs); a single large, dorsally applied kerf-cut cylinder (DKC); and a dorsomedially applied locking compression plate (DMLCP).

Micropore-induced capillarity enhances bone distribution in vivo in biphasic calcium phosphate scaffolds.

Unlabelled: The increasing demand for bone repair solutions calls for the development of efficacious bone scaffolds. Biphasic calcium phosphate (BCP) scaffolds with both macropores and micropores (MP) have improved healing compared to those with macropores and no micropores (NMP), but the role of micropores is unclear. Here, we evaluate capillarity induced by micropores as a mechanism that can affect bone growth in vivo.

Arthrodesis of the equine centrodistal and tarsometatarsal joints using a single modified kerf-cut cylinder.

Objectives: To describe a technique for surgical placement of a modified kerf-cut cylinder for the purpose of arthrodesis across the equine centrodistal and tarsometatarsal joints.

Methods: Each horse (n = 4) underwent unilateral placement of a single kerf-cut cylinder spanning the centrodistal and tarsometatarsal joints with the placement of an autologous cancellous bone graft. Horses were evaluated via lameness examination and radiography postoperatively and euthanatization of each horse was performed at four different time points up to 12 weeks post-surgery to evaluate for lameness, implant stability and success with integration in the surrounding bone.

3D FSE Cube and VIPR-aTR 3.0 Tesla magnetic resonance imaging predicts canine cranial cruciate ligament structural properties.

Estimation of cranial cruciate ligament (CrCL) structural properties in client-owned dogs with incipient cruciate rupture would be advantageous. The objective of this study was to determine whether magnetic resonance imaging (MRI) measurement of normal CrCL volume in an ex-vivo canine model predicts structural properties. Stifles from eight dogs underwent 3.

Mechanical Evaluation of Locking, Nonlocking, and Hybrid Plating Constructs Using a Locking Compression Plate in a Canine Synthetic Bone Model.

Objective: To evaluate the mechanical properties of locking screw placement in hybrid plating in comparison to all-locked and all nonlocked constructs.

Study Design: Completely randomized design. Forty-eight synthetic bone cylinders (4th generation composite Sawbones(®)) across 6 construct types (n = 8 each).

In Vivo Measures of Shear Wave Speed as a Predictor of Tendon Elasticity and Strength.

The purpose of this study was to assess the potential for ultrasound shear wave elastography (SWE) to measure tissue elasticity and ultimate stress in both intact and healing tendons. The lateral gastrocnemius (Achilles) tendons of 41 New Zealand white rabbits were surgically severed and repaired with growth factor coated sutures. SWE imaging was used to measure shear wave speed (SWS) in both the medial and lateral tendons pre-surgery, and at 2 and 4 wk post-surgery.

Biomechanical evaluation of a novel subcuticular skin stapling device for use in equine abdominal surgeries.

Objective: To compare the in vitro biomechanical properties of a novel subcuticular stapling device to current methods of abdominal skin closure for equine abdominal surgery.

Study Design: In vitro randomized, matched design.

Sample Population: Equine ventral median abdominal skin specimens (n = 24 horses).

Computed tomographic imaging of subchondral fatigue cracks in the distal end of the third metacarpal bone in the thoroughbred racehorse can predict crack micromotion in an ex-vivo model.

Articular stress fracture arising from the distal end of the third metacarpal bone (MC3) is a common serious injury in Thoroughbred racehorses. Currently, there is no method for predicting fracture risk clinically. We describe an ex-vivo biomechanical model in which we measured subchondral crack micromotion under compressive loading that modeled high speed running.

Controlled multiple growth factor delivery from bone tissue engineering scaffolds via designed affinity.

It is known that angiogenesis plays an important role in bone regeneration and that release of angiogenic and osteogenic growth factors can enhance bone formation. Multiple growth factors play key roles in processes that lead to tissue formation/regeneration during natural tissue development and repair. Therefore, treatments aiming to mimic tissue regeneration can benefit from multiple growth factor release, and there remains a need for simple clinically relevant approaches for dual growth factor release.

Percutaneous lovastatin accelerates bone healing but is associated with periosseous soft tissue inflammation in a canine tibial osteotomy model.

Experimental studies have shown the ability of statins to stimulate bone formation when delivered locally or in large oral doses, however most have been studied in rodents. This anabolic effect is through the selective activation of BMP-2. Our purpose was to determine the effects of local treatment with lovastatin on bone healing in mammals as a preclinical animal model.

Coating with a modular bone morphogenetic peptide promotes healing of a bone-implant gap in an ovine model.

Despite the potential for growth factor delivery strategies to promote orthopedic implant healing, there is a need for growth factor delivery methods that are controllable and amenable to clinical translation. We have developed a modular bone growth factor, herein termed "modular bone morphogenetic peptide (mBMP)", which was designed to efficiently bind to the surface of orthopedic implants and also stimulate new bone formation. The purpose of this study was to coat a hydroxyapatite-titanium implant with mBMP and evaluate bone healing across a bone-implant gap in the sheep femoral condyle.

Evaluation of submucosally injected polyethylene glycol-based hydrogel and bovine cross-linked collagen in the canine urethra using cystoscopy, magnetic resonance imaging and histopathology.

Objective: To (1) investigate the tissue response to a novel urethral bulking agent, polyethylene glycol carboxymethyl cellulose hydrogel (PEG-CMC) injected submucosally in the canine urethra and (2) compare PEG-CMC with bovine collagen (BC), the current standard for urethral bulking.

Study Design: Experimental study.

Animals: Purpose-bred female hound dogs (n = 8).

Detection of articular pathology of the distal aspect of the third metacarpal bone in thoroughbred racehorses: comparison of radiography, computed tomography and magnetic resonance imaging.

Objective: To compare digital radiography (DR), computed tomography (CT), and magnetic resonance imaging (MRI) for detection of pathology of the distal aspect of the third metacarpal bone (MC3) and to assess whether arthrography would improve detection of articular cartilage or subchondral bone cracking.

Study Design: Cross-sectional study.

Sample Population: Limb specimens from 17 Thoroughbred horses after catastrophic injury and 4 age-matched control horses.

Synovitis in dogs with stable stifle joints and incipient cranial cruciate ligament rupture: a cross-sectional study.

Objective: To evaluate stifle joints of dogs for synovitis, before development of joint instability and cranial cruciate ligament rupture (CrCLR).

Study Design: Cross-sectional study.

Animals: Dogs (n = 16) with CrCLR and stable contralateral stifles; 10 control dogs with intact CrCL.

Are bacterial load and synovitis related in dogs with inflammatory stifle arthritis?

It has been proposed that small quantities of microbial material within synovial joints may act as a trigger for development of synovitis. We have previously identified an association between intra-articular bacteria and development of inflammatory stifle arthritis and cranial cruciate ligament rupture (CCLR) in dogs, and now wished to quantify bacterial load and markers of synovitis in dogs with and without stifle arthritis and CCLR. Joint tissues were collected from dogs with CCLR (n=51) and healthy dogs with normal stifles (n=9).