2023 International Consensus Meeting on musculoskeletal infection: Summary from the treatment workgroup and consensus on treatment in preclinical models.

In vitro and in vivo studies are critical for the preclinical efficacy assessment of novel therapies targeting musculoskeletal infections (MSKI). Many preclinical models have been developed and applied as a prelude to evaluating safety and efficacy in human clinical trials. In performing these studies, there is both a requirement for a robust assessment of efficacy, as well as a parallel responsibility to consider the burden on experimental animals used in such studies. Since MSKI is a broad term encompassing infections varying in pathogen, anatomical location, and implants used, there are also a wide range of animal models described modeling these disparate infections. Although some of these variations are required to adequately evaluate specific interventions, there would be enormous value in creating a unified and standardized criteria to animal testing in the treatment of MSKI. The Treatment Workgroup of the 2023 International Consensus Meeting on Musculoskeletal Infection was responsible for questions related to preclinical models for treatment of MSKI. The main objective was to review the literature related to priority questions and estimate consensus opinion after voting. This document presents that process and results for preclinical models related to (1) animal model considerations, (2) outcome measurements, and (3) imaging.

Low-speed instrumented drill press for bone screw insertion.

Screw insertion torque is a widely used/effective method for quantifying fixation strength in orthopedic implant research for different screw geometries, implantation sites, and loads. This work reports the construction of an open-source instrumented benchtop screw insertion device for a total cost of $7545 ($492 + $7053 for equipped sensors), as well as validation of the device and an example use-application. The insertion device is capable of recording the axial load, rotational speed, and applied torque throughout the screw insertion process at 10 samples per second, as demonstrated in the validation test. For this combination of bone analog (20 PCF Sawbones©), screw, and loading, the resolution of the torque sensor was 25% of the maximum measured torque; a different model torque sensor would be required to meet ASTM F543-17, which specifies a resolution of 10% of the maximum torque. This system is optimized for fastener insertion at speeds of 120 rpm or less and axial loading up to 50 N.

Laser microgrooving and resorbable blast texturing for enhanced surface function of titanium alloy for dental implant applications.

Long-term dental implant success is dependent on biocompatibility and osseointegration between the bone and the implant. Surface modifications such as laser-induced microgrooving which increase contact area can enhance osseointegration by establishing and directing a stable attachment between the implant surface and peri-implant bone. The objective of this study was to evaluate pre-osteoblast proliferation, morphology, and differentiation on titanium alloy (Ti64) surfaces-Laser-Lok© (LL), resorbable blast textured (RBT), and machined (M)-compared to tissue culture plastic (TCP) control. We hypothesized the LL surfaces would facilitate increased cellular alignment compared to all other groups, and LL and RBT surfaces would demonstrate enhanced proliferation and differentiation compared to M and TCP surfaces. Surface roughness was quantified using a surface profilometer, and water contact angle was measured to evaluate the hydrophilicity of the surfaces. Cellular function was assessed using quantitative viability and differentiation assays and image analyses, along with qualitative fluorescent (viability and cytoskeletal) imaging and scanning electron microscopy. No differences in surface roughness were observed between groups. Water contact angle indicated LL was the least hydrophilic surface, with RBT and M surfaces exhibiting greater hydrophilicity. Cell proliferation on day 2 was enhanced on both LL and RBT surfaces compared to M, and all three groups had higher cell numbers on day 2 compared to day 1. Cell orientation was driven by the geometry of the surface modification, as cells were more highly aligned on LL surfaces compared to TCP (on day 2) and RBT (on day 3). At day 21, cell proliferation was greater on LL, RBT, and TCP surfaces compared to M, though no differences in osteogenic differentiation were observed. Collectively, our results highlight the efficacy of laser microgrooved and resorbable blast textured surface modifications of Ti64 for enhancing cellular functions, which may facilitate improved osseointegration of dental implants.

Amniotic membrane attenuates heterotopic ossification following high-dose bone morphogenetic protein-2 treatment of segmental bone defects.

Treatment of large bone defects with supraphysiological doses of bone morphogenetic protein-2 (BMP-2) has been associated with complications including heterotopic ossification (HO), inflammation, and pain, presumably due to poor spatiotemporal control of BMP-2. We have previously recapitulated extensive HO in our rat femoral segmental defect model by treatment with high-dose BMP-2 (30 µg). Using this model and BMP-2 dose, our objective was to evaluate the utility of a clinically available human amniotic membrane (AM) around the defect space for guided bone regeneration and reduction of HO. We hypothesized that AM surrounding collagen sponge would attenuate heterotopic ossification compared with collagen sponge alone. In vitro, AM retained more BMP-2 than a synthetic poly(ε-caprolactone) membrane through 21 days. In vivo, as hypothesized, the collagen + AM resulted in significantly less heterotopic ossification and correspondingly, lower total bone volume (BV), compared with collagen sponge alone. Although bone formation within the defect was delayed with AM around the defect, by 12 weeks, defect BVs were equivalent. Torsional stiffness was significantly reduced with AM but was equivalent to that of intact bone. Collagen + AM resulted in the formation of dense fibrous tissue and mineralized tissue, while the collagen group contained primarily mineralized tissue surrounded by marrow-like structures. Especially in conjunction with high doses of growth factor delivered via collagen sponge, these findings suggest AM may be effective as an overlay adjacent to bone healing sites to spatially direct bone regeneration and minimize heterotopic ossification.

Increase in serum nerve growth factor but not intervertebral disc degeneration following whole-body vibration in rats.

BACKGROUND: Low back pain is a leading cause of disability and is frequently associated with whole-body vibration exposure in industrial workers and military personnel. While the pathophysiological mechanisms by which whole-body vibration causes low back pain have been studied in vivo, there is little data to inform low back pain diagnosis. Using a rat model of repetitive whole-body vibration followed by recovery, our objective was to determine the effects of vibration frequency on hind paw withdrawal threshold, circulating nerve growth factor concentration, and intervertebral disc degeneration. METHODS: Male Sprague-Dawley rats were vibrated for 30 min at an 8 Hz or 11 Hz frequency every other day for two weeks and then recovered (no vibration) for one week. Von Frey was used to determine hind paw mechanical sensitivity every two days. Serum nerve growth factor concentration was determined every four days. At the three-week endpoint, intervertebral discs were graded histologically for degeneration. FINDINGS: The nerve growth factor concentration increased threefold in the 8 Hz group and twofold in the 11 Hz group. The nerve growth factor concentration did not return to baseline by the end of the one-week recovery period for the 8 Hz group. Nerve growth factor serum concentration did not coincide with intervertebral disc degeneration, as no differences in degeneration were observed among groups. Mechanical sensitivity generally decreased over time for all groups, suggesting a habituation (desensitization) effect. INTERPRETATION: This study demonstrates the potential of nerve growth factor as a diagnostic biomarker for low back pain due to whole-body vibration.

Biomechanical Comparison of a Headless Compression Screw Fastener and AO Cortical Bone Screw for Fixation of a Simulated Equine Third Carpal Bone Slab Fracture.

Frontal plane slab fractures account for the majority of third carpal bone (C3) fractures in racing and performance horses. Recommended treatment is stabilization with a lagged AO cortical screw. Associated complications are fragment splitting, fragment spinning, and irritation of dorsal soft tissue structures. A novel, headless, cannulated screw with interlocking threads the Headless Compression Screw Fastener (HCSF) has been developed to resist multidirectional forces and bending moments; however, it has not been applied in the horse. Simulated C3 frontal plane slab fractures were created in nine paired carpi from equine cadaver limbs, fixed with either the HCSF or AO cortical bone screw, and loaded in shear to failure. The effect of screw type on stiffness, maximum load to failure, and yield load was assessed in separate linear mixed models. No significant (P< .05) difference between screw types was detected in terms of maximum load to failure (P= .084), stiffness (P= .26), or yield load (P= .088). Mode of failure was screw bending in all specimens. For some samples in both groups, failure was associated with the sagittal fracture at the screw-bone interface. The HCSF was successfully used to repair simulated third carpal bone fractures. The different head and thread pitches of the HCSF effectively compressed the fracture. The headless design eliminates the need for counter sinking. There was no significant difference in maximum load to failure, stiffness, nor yield load compared to the cortical screws. These results invite clinical application to be investigated.

Review of immunological plasma markers for longitudinal analysis of inflammation and infection in rat models.

Disease or trauma of orthopedic tissues, including osteomyelitis, osteoporosis, arthritis, and fracture, results in a complex immune response, leading to a change in the concentration and milieu of immunological cells and proteins in the blood. While C-reactive protein levels and white blood cell counts are used to track inflammation and infection clinically, controlled longitudinal studies of disease/injury progression are limited. Thus, the use of clinically-relevant animal models can enable a more in-depth understanding of disease/injury progression and treatment efficacy. Though longitudinal tracking of immunological markers has been performed in rat models of various inflammatory and infectious diseases, currently there is no consensus on which markers are sensitive and reliable for tracking levels of inflammation and/or infection. Here, we discuss the blood markers that are most consistent with other outcome measures of the immune response in the rat, by reviewing their utility for longitudinal tracking of infection and/or inflammation in the following types of models: localized inflammation/arthritis, injury, infection, and injury + infection. While cytokines and acute phase proteins such as haptoglobin, fibrinogen, and α2 -macroglobulin demonstrate utility for tracking immunological response in many inflammation and infection models, there is likely not a singular superior marker for all rat models. Instead, longitudinal characterization of these models may benefit from evaluation of a collection of cytokines and/or acute phase proteins. Identification of immunological plasma markers indicative of the progression of a pathology will allow for the refinement of animal models for understanding, diagnosing, and treating inflammatory and infectious diseases of orthopedic tissues.

Ex vivo biomechanical comparison of four Center of Rotation Angulation Based Leveling Osteotomy fixation methods.

OBJECTIVE: To compare the strength of four constructs used to secure an osteotomy in a Center of Rotation Angulation (CORA)-Based Leveling Osteotomy (CBLO) in an ex vivo model. STUDY DESIGN: Ex vivo study. SAMPLE POPULATION: Thirty-two canine tibiae from 17 skeletally mature cadavers weighing between 18 and 33.2 kg. METHODS: Thirty-two paired tibiae with patella and patellar tendon were collected. Each tibia was randomly allocated to a construct group: plate and pin (Plate), plate with countersink compression screw (HCS), plate with tension band (TB), or plate with HCS and TB (HCSTB). Samples were loaded by distraction until failure. The stiffness, yield load, and ultimate load were compared between each fixation method. RESULTS: No difference in stiffness of the constructs was detected between groups (p = .6937). Yield load for the HCSTB group (1211.06 N) was greater than the TB group (1016.41 N), the HCS group (907.20 N), and the Plate group (787.73 N) (p = .0069). The ultimate load for the HCSTB group (1387.82 N) was greater than the TB group (1076.36 N), HCS group (926.62 N), and the Plate group (774.35 N) (p = .0004). CONCLUSIONS: CBLO fixation augmented with a TB and HCS provided a stronger construct that withstood a greater yield load and ultimate load than either augmentation strategy alone. CLINICAL SIGNIFICANCE: Augmenting a CBLO fixation with a TB and a HCS can provide increased construct strength.

Deleterious effects of whole-body vibration on the spine: A review of in vivo, ex vivo, and in vitro models.

Occupational exposure to whole-body vibration is associated with the development of musculoskeletal, neurological, and other ailments. Low back pain and other spine disorders are prevalent among those exposed to whole-body vibration in occupational and military settings. Although standards for limiting exposure to whole-body vibration have been in place for decades, there is a lack of understanding of whole-body vibration-associated risks among safety and healthcare professionals. Consequently, disorders associated with whole-body vibration exposure remain prevalent in the workforce and military. The relationship between whole-body vibration and low back pain in humans has been established largely through cohort studies, for which vibration inputs that lead to symptoms are rarely, if ever, quantified. This gap in knowledge highlights the need for the development of relevant in vivo, ex vivo, and in vitro models to study such pathologies. The parameters of vibrational stimuli (eg, frequency and direction) play critical roles in such pathologies, but the specific cause-and-effect relationships between whole-body vibration and spinal pathologies remain mostly unknown. This paper provides a summary of whole-body vibration parameters; reviews in vivo, ex vivo, and in vitro models for spinal pathologies resulting from whole-body vibration; and offers suggestions to address the gaps in translating injury biomechanics data to inform clinical practice.

Physicochemical and Antimicrobial Properties of Thermosensitive Chitosan Hydrogel Loaded with Fosfomycin.

Thermosensitive chitosan hydrogels-renewable, biocompatible materials-have many applications as injectable biomaterials for localized drug delivery in the treatment of a variety of diseases. To combat infections such as Staphylococcus aureus osteomyelitis, localized antibiotic delivery would allow for higher doses at the site of infection without the risks associated with traditional antibiotic regimens. Fosfomycin, a small antibiotic in its own class, was loaded into a chitosan hydrogel system with varied beta-glycerol phosphate (ß-GP) and fosfomycin (FOS) concentrations. The purpose of this study was to elucidate the interactions between FOS and chitosan hydrogel. The Kirby Bauer assay revealed an unexpected concentration-dependent inhibition of S. aureus, with reduced efficacy at the high FOS concentration but only at the low ß-GP concentration. No effect of FOS concentration was observed for the planktonic assay. Rheological testing revealed that increasing ß-GP concentration increased the storage modulus while decreasing gelation temperature. NMR showed that FOS was removed from the liquid portion of the hydrogel by reaction over 12 h. SEM and FTIR confirmed gels degraded and released organophosphates over 5 days. This work provides insight into the physicochemical interactions between fosfomycin and chitosan hydrogel systems and informs selection of biomaterial components for improving infection treatment.

Innovations in osteomyelitis research: A review of animal models.

Infection of bone tissue, or osteomyelitis, has become a growing concern in modern healthcare due in no small part to a rise in antibiotic resistance among bacteria, notably Staphylococcus aureus. The current standard of care involves aggressive, prolonged antibiotic therapy combined with surgical debridement of infected tissues. While this treatment may be sufficient for resolving a portion of cases, recurrences of the infection and associated risks including toxicity with long-term antibiotic usage have been reported. Therefore, there exists a need to produce safer, more efficacious options of treatment for osteomyelitis. In order to test treatment regimens, animal models that closely mimic the clinical condition and allow for accurate evaluation of therapeutics are necessary. Establishing a model that replicates features of osteomyelitis in humans continues to be a challenge to scientists, as there are many variables involved, including choosing an appropriate species and method to establish infection. This review addresses the refinement of animal models of osteomyelitis to reflect the clinical disease and test prospective therapeutics. The aim of this review is to explore studies regarding the use of animals for osteomyelitis therapeutics research and encourage further development of such animal models for the translation of results from the animal experiment to human medicine.

Alkali treatment facilitates functional nano-hydroxyapatite coating of 3D printed polylactic acid scaffolds.

Autografting is currently the gold standard for treatment of bone defects, but has shown disadvantages in the limited volume of and donor site morbidity associated with harvested bone. Customized bone scaffolds that mimic the mechanical and biological properties of native bone are needed to augment the currently limited bone regeneration strategies. To achieve this goal, a repeated cross-hatch structure with uniform cubic pores was designed and 3D printed using polylactic acid (PLA) via fused deposition modeling (FDM). PLA surfaces were modified by wet chemical (alkali) treatment for either 1 h (1hAT) or 6 h (6hAT), followed by coating with nano-hydroxyapatite (nHA). Our hypotheses were that: (i) 6-hour (but not 1-hour) alkali treatment would enhance nHA coating, (ii) the nHA coating on the 6-hour alkali-treated surface would increase hydrophilicity and cell attachment/proliferation, and (iii) stiffness, but not effective Young's modulus, would be reduced by 6-hour alkali treatment. The effects of AT and nHA coating on scaffold morphology was observed by scanning electron microscopy and quantified using a custom MATLAB script. Chemical composition and hydrophilicity were evaluated via energy dispersive X-ray spectroscopy and Fourier transform infrared spectroscopy, and water contact angle analyses, respectively. Mechanical testing and in vitro cell culture were further employed to analyze compressive properties, and cell attachment and proliferation, respectively. As expected, 6hAT led to reduced strut width and stiffness, while improving the nHA coating and hydrophilicity. Interestingly, PLA/6hAT but not PLA/6hAT/nHA demonstrated a reduction in effective modulus compared to PLA and PLA/nHA scaffolds. From in vitro experiments, the combined PLA/6hAT/nHA modification resulted in the greatest extent of cell attachment but not proliferation. These results collectively demonstrate that the PLA/6hAT/nHA scaffold exhibits properties that may prove beneficial for cancellous bone regeneration.

Autoclaving of Poloxamer 407 hydrogel and its use as a drug delivery vehicle.

With antibiotic-resistant bacteria becoming increasingly prevalent, biomaterials capable of targeted, in situ drug delivery are urgently needed. The synthetic polymer Poloxamer 407 (P407) is of particular interest due to its thermoreversible gelation. Clinical use of P407 typically involves sterilization via autoclaving, but the effects of these extreme environmental conditions on hydrogel water content, rheological properties and efficacy as a drug delivery vehicle remain unknown. The aim of this study was to investigate the effects of autoclaving on the properties of P407 hydrogel. Autoclaving reduced hydrogel water content due to evaporation, thus increasing the polymer weight fraction of the hydrogels. In contrast, except for a reduction in gelation temperature following autoclaving, autoclaved hydrogels had similar rheological properties as nonautoclaved hydrogels. In vitro, autoclaving did not hinder the hydrogel's efficacy as a carrier for vancomycin antibiotic, and P407 (with and without vancomycin) had a bactericidal effect on planktonic Staphylococcus aureus. An in vivo pilot study using P407 to deliver bacteriophage highlighted the need for additional understanding of the functionality of the hydrogel for surgical applications. In conclusion, P407 hydrogel water content and gelation temperature were reduced by autoclave sterilization, while other rheological properties and the efficacy of the biomaterial as a delivery vehicle for vancomycin in vitro were unaffected.

Therapeutics and delivery vehicles for local treatment of osteomyelitis.

Osteomyelitis, or the infection of the bone, presents a major complication in orthopedics and may lead to prolonged hospital visits, implant failure, and in more extreme cases, amputation of affected limbs. Typical treatment for this disease involves surgical debridement followed by long-term, systemic antibiotic administration, which contributes to the development of antibiotic-resistant bacteria and has limited ability to eradicate challenging biofilm-forming pathogens including Staphylococcus aureus-the most common cause of osteomyelitis. Local delivery of high doses of antibiotics via traditional bone cement can reduce systemic side effects of an antibiotic. Nonetheless, growing concerns over burst release (then subtherapeutic dose) of antibiotics, along with microbial colonization of the nondegradable cement biomaterial, further exacerbate antibiotic resistance and highlight the need to engineer alternative antimicrobial therapeutics and local delivery vehicles with increased efficacy against, in particular, biofilm-forming, antibiotic-resistant bacteria. Furthermore, limited guidance exists regarding both standardized formulation protocols and validated assays to predict efficacy of a therapeutic against multiple strains of bacteria. Ideally, antimicrobial strategies would be highly specific while exhibiting a broad spectrum of bactericidal activity. With a focus on S. aureus infection, this review addresses the efficacy of novel therapeutics and local delivery vehicles, as alternatives to the traditional antibiotic regimens. The aim of this review is to discuss these components with regards to long bone osteomyelitis and to encourage positive directions for future research efforts.

CRISPR-Cas9 modified bacteriophage for treatment of Staphylococcus aureus induced osteomyelitis and soft tissue infection.

Osteomyelitis, or bone infection, is often induced by antibiotic resistant Staphylococcus aureus strains of bacteria. Although debridement and long-term administration of antibiotics are the gold standard for osteomyelitis treatment, the increase in prevalence of antibiotic resistant bacterial strains limits the ability of clinicians to effectively treat infection. Bacteriophages (phages), viruses that in a lytic state can effectively kill bacteria, have gained recent attention for their high specificity, abundance in nature, and minimal risk of host toxicity. Previously, we have shown that CRISPR-Cas9 genomic editing techniques could be utilized to expand temperate bacteriophage host range and enhance bactericidal activity through modification of the tail fiber protein. In a dermal infection study, these CRISPR-Cas9 phages reduced bacterial load relative to unmodified phage. Thus we hypothesized this temperate bacteriophage, equipped with the CRISPR-Cas9 bactericidal machinery, would be effective at mitigating infection from a biofilm forming S. aureus strain in vitro and in vivo. In vitro, qualitative fluorescent imaging demonstrated superiority of phage to conventional vancomycin and fosfomycin antibiotics against S. aureus biofilm. Quantitative antibiofilm effects increased over time, at least partially, for all fosfomycin, phage, and fosfomycin-phage (dual) therapeutics delivered via alginate hydrogel. We developed an in vivo rat model of osteomyelitis and soft tissue infection that was reproducible and challenging and enabled longitudinal monitoring of infection progression. Using this model, phage (with and without fosfomycin) delivered via alginate hydrogel were successful in reducing soft tissue infection but not bone infection, based on bacteriological, histological, and scanning electron microscopy analyses. Notably, the efficacy of phage at mitigating soft tissue infection was equal to that of high dose fosfomycin. Future research may utilize this model as a platform for evaluation of therapeutic type and dose, and alternate delivery vehicles for osteomyelitis mitigation.

Ex vivo biomechanical comparison of 2.7 mm string-of-pearl plate versus screw/wire/Polymethylmethacrylate composite fixation and 2.7 mm veterinary acetabular plate for repair of simulated canine acetabular fractures.

BACKGROUND: Acetabular fractures comprise 12-30% of canine pelvic fractures and require accurate anatomic reduction and rigid stability to ensure proper healing and minimize future osteoarthritis. Many techniques have been used to repair these fractures, with common techniques including veterinary acetabular plates or use of screw/wire/polymethylmethacrylate constructs. String-of-Pearl™ plating systems have also been used clinically but there is a lack of research supporting their use for these fractures. The purpose of this study was to compare fracture reduction accuracy, biomechanical characteristics, and mode of failure between String-of-Pearls™, veterinary acetabular plates, screw/wire/polymethylmethacrylate constructs in a simulated, ex-vivo acetabular fracture model. We hypothesized that the String-of-Pearls™ constructs would have equivalent or greater mechanical properties and reduction compared to the other constructs. RESULTS: The mean craniocaudal acetabular diameter before fixation (mean 25.2 mm; range 20 mm - 30.1 mm) was not significantly different from after fixation (mean 23.9 mm; range 20 mm - 28.3 mm) for any fixation method. Comparison of reduction scores between groups revealed no significant differences. No significant differences were noted for cyclical displacement or stiffness. There was significant difference with superior failure load of String-of-Pearls™ compared to screw/wire/polymethylmethacrylate in the 75th percentile of animal weight (P = 0.0021), and superior failure load of String-of-Pearls™ compared to veterinary acetabular plates in the 50th (P = 0.0232) and 75th percentiles (P = 0.0058). Stiffness of the String-of-Pearls™ construct was significantly greater than the veterinary acetabular plate construct (P = 0.0417). For ultimate load, String-of-Pearls™ constructs were significantly greater than screw/wire/polymethylmethacrylate (P = 0.0331) and veterinary acetabular plates (P = 0.0218). CONCLUSION: Although the ease of application for the String-of-Pearls™ implant was subjectively better than other implants, no significant differences were found in fracture reduction scores. The String-of-Pearls™ constructs were stiffer than veterinary acetabular plates and exhibited greater failure and ultimate loads compared to veterinary acetabular plates and screw/wire/polymethylmethacrylate fixations. The String-of-Pearls™ implant appears to be a suitable fixation choice for simple canine acetabular fractures.

Effects of short- and long-term administration of nonsteroidal anti-inflammatory drugs on osteotomy healing in dogs.

OBJECTIVE: To determine the influence of short-term administration of carprofen on bone healing in dogs. STUDY DESIGN: Randomized controlled experimental study. ANIMALS: Eighteen purpose-bred sexually mature hound dogs. METHODS: Tibial osteotomies were performed, and dogs were divided into three groups: no carprofen (n = 6), 2-week administration of carprofen at 2.2 mg/kg twice daily (n = 6), and 8-week administration of carprofen at 2.2 mg/kg twice daily (n = 5). Bone healing was evaluated radiographically at 4 and 8 weeks postoperatively. Postmortem, fracture healing was assessed via biomechanical testing (three-point bending), histological cartilage:callus ratio, and bone mineral density (BMD) with quantitative computed tomography. RESULTS: No biomechanical difference was detected between dogs that received no carprofen and those that received 2 weeks of carprofen or between those that received 2 weeks vs 8 weeks of carprofen. Stiffness (P = .035) and maximum stress (P = .042) were higher in dogs that received no carprofen than in those that received 8 weeks of carprofen. Radiographic healing did not differ between dogs without carprofen and those with 2-week administration of carprofen (P = .9923). However, tibias of dogs without carprofen and those with 2-week administration of carprofen were more healed compared with those in the 8-week-carprofen group at 4 and 8 weeks after surgery (P = .0011). No treatment effect was detected by cartilage:callus ratio or BMD. CONCLUSION: Long-term administration of carprofen had a negative effect on bone healing compared with short-term or no administration of carprofen. CLINICAL SIGNIFICANCE: Nonsteroidal anti-inflammatory drugs should be used cautiously in dogs at risk for delayed bone healing, and administration should be discontinued beyond the perioperative period in dogs with fractures or osteotomies.

Mechanical Response of Porcine Liver Tissue under High Strain Rate Compression.

In automobile accidents, abdominal injuries are often life-threatening yet not apparent at the time of initial injury. The liver is the most commonly injured abdominal organ from this type of trauma. In contrast to current safety tests involving crash dummies, a more detailed, efficient approach to predict the risk of human injuries is computational modelling and simulations. Further, the development of accurate computational human models requires knowledge of the mechanical properties of tissues in various stress states, especially in high-impact scenarios. In this study, a polymeric split-Hopkinson pressure bar (PSHPB) was utilized to apply various high strain rates to porcine liver tissue to investigate its material behavior during high strain rate compression. Liver tissues were subjected to high strain rate impacts at 350, 550, 1000, and 1550 s-1. Tissue directional dependency was also explored by PSHPB testing along three orthogonal directions of liver at a strain rate of 350 s-1. Histology of samples from each of the three directions was performed to examine the structural properties of porcine liver. Porcine liver tissue showed an inelastic and strain rate-sensitive response at high strain rates. The liver tissue was found lacking directional dependency, which could be explained by the isotropic microstructure observed after staining and imaging. Furthermore, finite element analysis (FEA) of the PSHPB tests revealed the stress profile inside liver tissue and served as a validation of PSHPB methodology. The present findings can assist in the development of more accurate computational models of liver tissue at high-rate impact conditions allowing for understanding of subfailure and failure mechanisms.

A biomechanical comparison of conventional dynamic compression plates and string-of-pearls™ locking plates using cantilever bending in a canine Ilial fracture model.

BACKGROUND: Fracture of the ilium is common orthopedic injury that often requires surgical stabilization in canine patients. Of the various methods of surgical stabilization available, application of a lateral bone plate to the ilium is the most common method of fixation. Many plating options are available, each having its own advantages and disadvantages. The purpose of this study was to evaluate the biomechanical properties of a 3.5 mm String-of-Pearls™ plate and a 3.5 mm dynamic compression plate in a cadaveric canine ilial fracture model. Hemipelves were tested in cantilever bending to failure and construct stiffness, yield load, displacement at yield, ultimate load, and mode of failure were compared. RESULTS: The mean stiffness of dynamic compression plate (116 ± 47 N/mm) and String-of-Pearls™ plate (107 ± 18 N/mm) constructs, mean yield load of dynamic compression plate (793 ± 333 N) and String-of-Pearls™ plate (860 ± 207 N) constructs, mean displacement at yield of dynamic compression plate (8.6 ± 3.0 mm) and String-of-Pearls™ plate (10.2 ± 2.8 mm) constructs, and ultimate load at failure of dynamic compression plate (936 ± 320 N) and String-of-Pearls™ plate (939 ± 191 N) constructs were not significantly different. No differences were found between constructs with respect to mode of failure. CONCLUSIONS: No significant biomechanical differences were found between String-of-Pearls™ plate and dynamic compression plate constructs in this simplified cadaveric canine ilial fracture model.

Identification of Extracellular Matrix Components and Biological Factors in Micronized Dehydrated Human Amnion/Chorion Membrane.

Objective: The use of bioactive extracellular matrix (ECM) grafts such as amniotic membranes is an attractive treatment option for enhancing wound repair. In this study, the concentrations, activity, and distribution of matrix components, growth factors, proteases, and inhibitors were evaluated in PURION® Processed, micronized, dehydrated human amnion/chorion membrane (dHACM; MiMedx Group, Inc.). Approach: ECM components in dHACM tissue were assessed by using immunohistochemical staining, and growth factors, cytokines, proteases, and inhibitors were quantified by using single and multiplex ELISAs. The activities of proteases that were native to the tissue were determined via gelatin zymography and EnzChek® activity assay. Results: dHACM tissue contained the ECM components collagens I and IV, hyaluronic acid, heparin sulfate proteoglycans, fibronectin, and laminin. In addition, numerous growth factors, cytokines, chemokines, proteases, and protease inhibitors that are known to play a role in the wound-healing process were quantified in dHACM. Though matrix metalloproteinases (MMPs) were present in dHACM tissues, inhibitors of MMPs overwhelmingly outnumbered the MMP enzymes by an overall molar ratio of 28:1. Protease activity assays revealed that the MMPs in the tissue existed primarily either in their latent form or complexed with inhibitors. Innovation: This is the first study to characterize components that function in wound healing, including inhibitor and protease content and activity, in micronized dHACM. Conclusion: A variety of matrix components and growth factors, as well as proteases and their inhibitors, were identified in micronized dHACM, providing a better understanding of how micronized dHACM tissue can be used to effectively promote wound repair.