Dehydrated Human Amniotic-Chorionic Membrane Reduces Incisional Hernia Formation in an Animal Model.

BACKGROUND: Currently there are no standard of care treatment strategies for IH prevention (IHP). Dehydrated human amnion-chorion (dHACM) is a healing adjunct that elutes growth factors including several that have reduced IH in animal models. We therefore performed a double-blinded, prospective randomized controlled trial (RCT) to test the hypothesis that dHACM significantly reduces IH formation in a well-studied animal model of acute IH. MATERIAL AND METHODS: Forty 16-week-old male Sprague-Dawley rats were randomized to one of four groups: No Treatment vs. dHACM Sheet (Group A), and Saline vs. dHACM Injection (Group B). Each animal underwent a 5-cm midline laparotomy which was incompletely closed with 5-0 plain gut sutures; this was performed by a surgeon blinded to treatment group (first blind). After 28 days, the primary endpoints of IH formation and hernia size were determined by study staff blinded to treatment (second blind). Secondary endpoints included healed fascia tensile strength as determined by tensiometry, systemic and local inflammatory markers as measured by ELISA, and fascial scar collagen I/III ratios per Western blotting. RESULTS: In Group A, No Treatment developed IH at 87.5% vs. 62.5% for Sheet (P = 0.28). Hernias that formed in the Sheet group were significantly smaller (P = 0.036). In Group B, Injection and Saline yielded identical IH rates of 77.8%. Molecular characterization of fascial scar demonstrated non-inferior tensile strength, collagen I/III ratios, and inflammatory markers in dHACM-treated animals. CONCLUSIONS: dHACM sheets significantly reduced the size of IH following laparotomy when compared to no treatment.

Experimental Model of Zygomatic and Mandibular Defects to Support the Development of Custom Three-Dimensional--Printed Bone Scaffolds.

INTRODUCTION: Autologous reconstruction of segmental craniomaxillofacial bone defects is limited by insufficient graft material, donor site morbidity, and need for microsurgery. Reconstruction is challenging due to the complex three-dimensional (3D) structure of craniofacial skeleton. Customized 3D-printed patient-specific biologic scaffolds hold promise for reconstruction of the craniofacial skeleton without donor site morbidity. The authors report a porcine craniofacial defect model suitable for further evaluation of custom 3D-printed engineered bone scaffolds. METHODS: The authors created a 6 cm critical load-bearing defect in the left mandibular angle and a 1.5 cm noncritical, nonload bearing defect in the contralateral right zygomatic arch in 4 Yucatan minipigs. Defects were plated with patient-specific titanium hardware based on preoperative CT scans. Serial CT imaging was done immediately postoperatively, and at 3 and 6 months. Animals were clinically assessed for masticatory function, ambulation, and growth. At the 6-month study endpoint, animals were euthanized, and bony regeneration was evaluated through histological staining and micro-CT scanning compared to contralateral controls. RESULTS: All 4 animals reached study endpoint. Two mandibular plates fractured, but did not preclude study completion due to loss of masticatory function. One zygoma plate loosened while the site of another underwent heterotopic ossification. Gross examination of site defects revealed heterotopic ossification, confirmed by histological and micro-CT evaluation. Biomechanical testing was unavailable due to insufficient bony repair. CONCLUSIONS: The presented porcine zygoma and mandibular defect models are incapable of repair in the absence of bone scaffolds. Based on the authors' results, this model is appropriate for further study of custom 3D-printed engineered bone scaffolds.

Extracorporeal shock wave therapy improves short-term limb use after canine tibial plateau leveling osteotomy.

OBJECTIVE: To determine the influence of postoperative extracorporeal shock wave therapy (ESWT) on hind limb use after tibial plateau leveling osteotomy (TPLO). STUDY DESIGN: Randomized, prospective clinical trial. ANIMALS: Sixteen client-owned dogs, 2 to 10 years old weighing 18 to 75 kg. METHODS: Dogs were randomly assigned to treatment cohorts, TPLO with ESWT (ESWT, n = 9) or TPLO without ESWT (control, n = 7). Treatment consisted of 1000 pulses at 0.15 mJ/mm2 immediately and 2 weeks after surgery. Subjective pain, stifle goniometry, stifle circumference, peak vertical force (PVF) and vertical impulse (VI) were measured before surgery, prior to ESWT, and 2 and 8 weeks after surgery. Measures were compared between treatments at each time point and among time points for each treatment (P < .05). RESULTS: The PVF (5.5 ± 1.0 N/kg, mean ± SD) and VI (0.67 ± 0.14 N-s/kg) of surgically treated limbs in the ESWT cohort were higher 8 weeks after surgery compared with preoperative (3.8 ± 1.1 N/kg, P < .0001 and 0.47 ± 0.21 N-s/kg, P = .0012, respectively) values. In the control cohort, PVF (2.9 ± 1.3 N/kg, P = .0001) and VI (0.33 ± 0.20 N-s/kg, P = .0003) 2 weeks after surgery and VI (0.42 ± 0.2 N-s/kg, P = .0012) 8 weeks after surgery were lower (4.59 ± 2.33 N/kg and 0.592 ± 0.35 N-s/kg, respectively) than before surgery. Other parameters did not differ between groups. CONCLUSION: Weight bearing increased faster after TPLO in dogs treated with postoperative ESWT. CLINICAL SIGNIFICANCE: This study provides evidence to consider adjunct ESWT after TPLO.

Laboratory procedures update on Hirschsprung disease.

OBJECTIVES: The detection of ganglion cells in rectal biopsies of infants or toddlers with severe constipation is routinely performed by pediatric pathologists in many institutions. Hirschsprung disease (HD) is defined by the lack of ganglion cells (aganglionosis). The early recognition and the prompt implementation of surgical procedures obviously protect infants affected with HD from potential life-threatening conditions, including enterocolitis and debilitating constipation. Image-based and non-image-based clinical techniques and some laboratory tests have been reevaluated along the years, but often fragmentarily. Immunohistochemical markers have been increasingly used in pathology laboratories to detect ganglion cells and nerve fibers. Recently, calretinin, a vitamin D-dependent calcium-binding protein with expression in ganglion cells and nerves, has been described as an adjunctive or primary diagnostic test in HD. The aim of the present study was to systematically summarize and update laboratory procedures targeting ganglion cells in rectal biopsies. METHODS: Procedures and tests have been reviewed and values of specificity and sensitivity have been calculated according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Contrast enema has the lowest sensitivity and specificity of all of the 3-index investigations under the lens: contrast enema, anorectal manometry, and biopsy with histology. The latter procedure seems to have the highest sensitivity and specificity. Acetylcholinesterase staining on fresh-frozen material has been found to have slightly higher rates of sensitivity and specificity when compared with hematoxylin and eosin only. Calretinin staining may be supportive for the diagnosis, although some cases with false-positivity may be of some concern. CONCLUSIONS: Hematoxylin and eosin with or without acetylcholinesterase remains the criterion standard according to our PRISMA-based data. In our opinion, the number of false-positive results with potential overtreatment may limit the increasing advocacy for calretinin staining. Both the "primum non nocere" dictum and the "loss aversion heuristic" need to be satisfied harmoniously by preventing harm from unnecessary surgery.

Feline Adult Adipose Tissue-Derived Multipotent Stromal Cell Isolation and Differentiation.

Cats are among the most popular household pets. However, compared to other species, there is little information specific to feline adult mesenchymal stromal/stem cells. Despite the phylogenetic distance between domesticated cats, Felis silvestris catus, and humans, they share some similar health challenges like kidney disease, asthma, and diabetes. Investigative efforts have been focused on adult adipose-derived stromal/stem cell (ASC) therapies to address feline illnesses, including de novo pancreatic tissue generation for diabetes treatment. Given the relatively small size of domestic cats, optimized cell isolation from small quantities of adipose tissue is important in the development of feline ASC-based therapies. Additionally, there are unique features of feline ASC culture conditions and characterization. This chapter contains a few of the novel aspects of feline ASC isolation, culture, preservation, and differentiation.

Viable tendon neotissue from adult adipose-derived multipotent stromal cells.

Background: Tendon healing is frequently prolonged, unpredictable, and results in poor tissue quality. Neotissue formed by adult multipotent stromal cells has the potential to guide healthy tendon tissue formation. Objectives: The objective of this study was to characterize tendon neotissue generated by equine adult adipose-derived multipotent stromal cells (ASCs) on collagen type I (COLI) templates under 10% strain in a novel bioreactor. The tested hypothesis was that ASCs assume a tendon progenitor cell-like morphology, express tendon-related genes, and produce more organized extracellular matrix (ECM) in tenogenic versus stromal medium with perfusion and centrifugal fluid motion. Methods: Equine ASCs on COLI sponge cylinders were cultured in stromal or tenogenic medium within bioreactors during combined perfusion and centrifugal fluid motion for 7, 14, or 21 days under 10% strain. Viable cell distribution and number, tendon-related gene expression, and micro- and ultra-structure were evaluated with calcein-AM/EthD-1 staining, resazurin reduction, RT-PCR, and light, transmission, and scanning electron microscopy. Fibromodulin was localized with immunohistochemistry. Cell number and gene expression were compared between culture media and among culture periods (p < 0.05). Results: Viable cells were distributed throughout constructs for up to 21 days of culture, and cell numbers were higher in tenogenic medium. Individual cells had a round or rhomboid shape with scant ECM in stromal medium in contrast to clusters of parallel, elongated cells surrounded by highly organized ECM in tenogenic medium after 21 days of culture. Transcription factor, extracellular matrix, and mature tendon gene expression profiles confirmed ASC differentiation to a tendon progenitor-like cell in tenogenic medium. Construct micro- and ultra-structure were consistent with tendon neotissue and fibromodulin was present in the ECM after culture in tenogenic medium. Conclusion: Long-term culture in custom bioreactors with combined perfusion and centrifugal tenogenic medium circulation supports differentiation of equine adult ASCs into tendon progenitor-like cells capable of neotissue formation.

Shoe configuration effects on third phalanx and capsule motion of unaffected and laminitic equine hooves in-situ.

Equine shoes provide hoof protection and support weakened or damaged hoof tissues. Two hypotheses were tested in this study: 1) motion of the third phalanx (P3) and hoof wall deformation are greater in laminitic versus unaffected hooves regardless of shoe type; 2) P3 displacement and hoof wall deformation are greatest while unshod (US), less with open-heel (OH), then egg-bar (EB) shoes, and least with heart-bar (HB) shoes for both hoof conditions. Distal forelimbs (8/condition) were subjected to compressive forces (1.0x102-5.5x103 N) while a real-time motion detection system recorded markers on P3 and the hoof wall coronary band, vertical midpoint, and solar margin. Magnitude and direction of P3 displacement and changes in proximal and distal hemi-circumference, quarter and heel height and proximal and distal heel width were quantified. Hoof condition and shoe effects were assessed with 2-way ANOVA (p<0.05). P3 displacement was greater in laminitic hooves when US or with OH, and EB and HB reduced P3 displacement in laminitic hooves. P3 displacement was similar among shoes in unaffected hooves and greatest in laminitic hooves with OH, then US, EB and HB. EB and HB increased P3 displacement from the dorsal wall in unaffected hooves and decreased it in laminitic hooves. OH and EB increased P3 motion from the coronary band in laminitic hooves, and HB decreased P3 motion toward the solar margin in unaffected and laminitic hooves. In laminitic hooves, HB reduced distal hemi-circumference and quarter deformation and increased heel deformation and expansion. Proximal hemi-circumference constriction was inversely related to proximal heel expansion with and without shoes. Overall, shoe configuration alters hoof deformation distinctly between unaffected and laminitic hooves, and HB provided the greatest P3 stability in laminitic hooves. These unique results about P3 motion and hoof deformation in laminitic and unaffected hooves inform shoe selection and design.

Wrist motion is distinct between touch screen and manual or digital devices.

BACKGROUND: Restricted motion during touch screen device use may contribute to wrist overuse injuries. Wrist radioulnar deviation and extension while using touch screen devices and digital or manual counterparts in male and female medical professional dominant and non-dominant hands were quantified to test the hypothesis that mobile touch screen device use reduces wrist motion. METHODS: An active motion detection system was used to record wrist motion of 12 participants while: tablet swiping and turning book pages; raising a cell and traditional phone to the ear; texting and typing; and entering numbers on a cell phone and manual calculator. Medial and lateral wrist surface range of motion (ROM) and minimum and maximum wrist radial-ulnar deviation and flexion-extension were quantified. RESULTS: Device, sex and handedness effects were determined (P<0.05). Maximum medial radial deviation and ROM were greater using a cell versus traditional phone. Maximum medial radial deviation was higher in the nondominant wrist during backward tablet swiping and while backward page turning versus tablet swiping. Maximum and minimum medial extension angles and ROM were greater while typing versus texting. Female nondominant hand maximum lateral extension and ROM were greater for typing versus texting and maximum medial extension and lateral extension ROM greater during manual versus cell phone calculator use with handedness combined. Maximum lateral extension and ROM were greater in females versus males using manual calculators. CONCLUSIONS: Sex and handedness should instruct touch screen, digital and manual device design and use for optimal performance and injury prevention.

Hemodynamic Changes in Response to Hyperacute Spinal Trauma in a Swine Model.

Acute spinal cord injury (ASCI) is a devastating event that can have severe hemodynamic consequences, depending on location and severity of the lesion. Knowledge of hyperacute hemodynamic changes is important for researchers using porcine models of thoracic ASCI. The goal of this study was to determine the hyperacute hemodynamic changes observed after ASCI when using pigs as their own controls. Five Yucatan gilts were anesthetized, and a dorsal laminectomy performed at T10-T12. Standardized blunt trauma was applied for 5 consecutive min, and hemodynamic variables were collected 5 min before ASCI, and at 2, 4, 6, 8, 10, 20, 30, 60, 80 and 120 min after ASCI. Arterial blood gas samples were collected at 60 min and 10 min before, and at 30 min and between 120 and 240 min after ASCI. Parametric data were analyzed using a mixed effects model with time point as the fixed factor and subject as the random factor. We found no effect on heart rate, pulse pressure, SpO2, EtCO2, and respiratory rate between baseline and timepoints after ASCI. Diastolic arterial pressure, mean arterial pressure, and systolic arterial pressure fell significantly by 18%, 16%, and 15%, respectively, at 2 min after ASCI. However, none of the decrements in arterial pressures resulted in hypotension at any time point. Heart rate did not change significantly after ASCI. Blood glucose progressively increased to 50% above baseline between 120 and 240 minutes after ASCI. Low thoracic ASCI caused a consistent and statistically significant but clinically minor hyperacute decrease in arterial pressures (-15%) that did not produce hypotension or metabolic changes suggestive of tissue hypoperfusion. Our findings using this model suggest that mean arterial pressures should be maintained above 85 mm Hg prior to spinal trauma in order to avoid hypotensive states after ASCI.

Agmatine Administration Effects on Equine Gastric Ulceration and Lameness.

Osteoarthritis (OA) accounts for up to 60% of equine lameness. Agmatine, a decarboxylated arginine, may be a viable option for OA management, based on reports of its analgesic properties. Six adult thoroughbred horses, with lameness attributable to thoracic limb OA, received either daily oral phenylbutazone (6.6 mg/kg), agmatine sulfate (25 mg/kg) or a control for 30 days, with 21-day washout periods between treatments. Subjective lameness, thoracic limb ground reaction forces (GRF), plasma agmatine and agmatine metabolite levels were evaluated using an established rubric, a force platform, and mass spectrometry, respectively, before, during and after each treatment period. Gastric ulceration and plasma chemistries were evaluated before and after treatments. Braking GRFs were greater after 14 and 29 days of agmatine compared to phenylbutazone administration. After 14 days of phenylbutazone administration, vertical GRFs were greater than for agmatine or the control. Glandular mucosal ulcer scores were lower after agmatine than phenylbutazone administration. Agmatine plasma levels peaked between 30 and 60 min and were largely undetectable by 24 h after oral administration. In contrast, plasma citric acid levels increased throughout agmatine administration, representing a shift in the metabolomic profile. Agmatine may be a viable option to improve thoracic limb GRFs while reducing the risk of glandular gastric ulceration in horses with OA.

Computed tomography myelography technique and spinal morphometry in healthy Yucatan pigs.

Porcine models of spinal cord injury (SCI) have an irreplaceable role in the development of experimental therapies. There is little literature regarding CT myelogram (CTM) techniques in swine and morphometry in miniature swine has not been established. A CT-guided method for performing myelography as well as reference values for spinal morphometry in healthy Yucatan miniature swine is lacking. The goal of this study is to describe a CT-guided method of performing CTM in a porcine model of SCI and to establish spinal morphometric reference values in mature Yucatan pigs. Six healthy, Yucatan sows, 9 months of age, weighing between 39-57.7kg, with no history of spinal disease, spinal injury, or neurologic deficits on physical exam were used in this study. CT myelography was performed in each sow under general anesthesia. CT scout images were used to guide needle placement at the L3-L4 intervertebral site. Once correct needle placement was confirmed using a 1ml test injection, a full dose of iodinated contrast (0.3ml/kg) was injected slowly over a 2-minute time period. Morphometry was performed using area measurements of the spinal cord (SC), vertebral body (VB), dural sac (DS), and vertebral canal (VC) at the mid-body and the intervertebral disc space of each spinal segment. Of the quantitative measurements, the spinal cord surface area had the widest range of values and the greatest coefficient of variance (CV) while those parameters for the vertebral canal had a low CV. Of the morphometric ratios, the DS:VC, had the lowest CV while the spinal cord ratios to DS and VC had the highest (>30). The vertebral canal surface area and the dural space: vertebral canal ratio may serve as reference values in future studies using this animal model.

Point-of-care treatment of geometrically complex midfacial critical-sized bone defects with 3D-Printed scaffolds and autologous stromal vascular fraction.

Critical-sized midfacial bone defects present a unique clinical challenge due to their complex three-dimensional shapes and intimate associations with sensory organs. To address this challenge, a point-of-care treatment strategy for functional, long-term regeneration of 2 cm full-thickness segmental defects in the zygomatic arches of Yucatan minipigs is evaluated. A digital workflow is used to 3D-print anatomically precise, porous, biodegradable scaffolds from clinical-grade poly-ε-caprolactone and decellularized bone composites. The autologous stromal vascular fraction of cells (SVF) is isolated from adipose tissue extracts and infused into the scaffolds that are implanted into the zygomatic ostectomies. Bone regeneration is assessed up to 52 weeks post-operatively in acellular (AC) and SVF groups (BV/DV = 0.64 ± 0.10 and 0.65 ± 0.10 respectively). In both treated groups, bone grows from the adjacent tissues and restores the native anatomy. Significantly higher torque is required to fracture the bone-scaffold interface in the SVF (7.11 ± 2.31 N m) compared to AC groups (2.83 ± 0.23 N m). Three-dimensional microcomputed tomography analysis reveals two distinct regenerative patterns: osteoconduction along the periphery of scaffolds to form dense lamellar bone and small islands of woven bone deposits growing along the struts in the scaffold interior. Overall, this study validates the efficacy of using 3D-printed bioactive scaffolds with autologous SVF to restore geometrically complex midfacial bone defects of clinically relevant sizes while also highlighting remaining challenges to be addressed prior to clinical translation.

Sedation Characteristics of Intranasal Alfaxalone in Adult Yucatan Swine.

Compared with intravenous and intramuscular methods, intranasal administration of sedatives is a less invasive and nonpainful technique. In this prospective, randomized, crossover study, we evaluated the sedative characteristics of 2 doses (1 and 2 mg/kg) of alfaxalone administered intranasally to 7 adult Yucatan swine. We compared sedation scores before and after administration of alfaxalone and between groups by using a composite sedation scoring system (range, 0 to 12, with 12 being the highest level of sedation)). Pigs were randomly assigned to receive 2 doses of intranasal alfaxalone (1 mg/kg [A1]); 2 mg/kg [A2]) as 2 separate events in a crossover design with a 60-d washout period. Categories scored were posture, palpebral droop, uninhibited behavior, drowsiness, and acceptance of anesthetic facemask. Sedation scores were collected before sedation was administered and then every 3 min for 30 min afterward. Instilled volumes (mean ± 1 SD) were 5.7 ± 0.5 and 11.3 ± 0.8 mL for A1 and A2, respectively. Both alfaxalone doses produced significant increases in sedation scores compared with baseline. Median sedation scores for A1 (6; range, 4-12) were not different from those for A2 (6; range, 6 to 12). Intranasal administration of alfaxalone as the sole sedative agent increased sedation scores from baseline, achieving peak sedation at 6 to 9 min after instillation of A2. However, sedation scores were similar between the 2 groups, and neither dose produced sufficient sedation to facilitate handling or the performance of any clinical procedures. Given the concentration of alfaxalone solution currently available, volume is the major limiting factor regarding testing higher doses of this drug for its use as a sole sedative agent in swine.

Assessment of the effect of horseshoes with and without traction adaptations on the gait kinetics of nonlame horses during a trot on a concrete runway.

OBJECTIVE: To assess the effect of horseshoes with and without traction adaptations on the gait kinetics of nonlame horses during a trot on a concrete runway. ANIMALS: 5 nonlame adult light-breed horses. PROCEDURES: Kinetic data were obtained for each horse when it was trotted across a force platform within a concrete runway unshod (control) and shod with standard horseshoes; standard horseshoes with high profile-low surface area calks, with low profile-high surface area calks, and coated with a thin layer of tungsten carbide (TLTC); and plastic-steel composite (PSC) horseshoes. Kinetic data were obtained for the control treatment first, then for each of the 5 shoe types, which were applied to each horse in a random order. Kinetic variables were compared among the 6 treatments. RESULTS: Body weight distribution did not differ among the 6 treatments. Compared with the control, the greatest increase in forelimb peak vertical force was observed when horses were shod with PSC shoes. In the hind limbs, the greatest increase in peak braking force was observed when horses were shod with PSC shoes, followed by the TLTC and low profile-high surface area calked shoes. The PSC shoes yielded the greatest coefficient of friction in both the forelimbs and hind limbs. Stance time was longest when horses were shod with standard shoes. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that PSC and TLTC shoes provided the best hoof protection and traction and might be good options for horses that spend a large amount of time traversing paved surfaces.

Association of Chronic Myelogenous (Basophilic) Leukemia and the BCR/ABL Mutation in a Yucatan Barrow (Sus scrofa domestica).

Background: Chronic myelogenous leukemia (CML) is a clonal proliferative disorder of the myeloid, megakaryocyte, and erythroid lineages. The onset and subsequent progression of CML is well-described in humans. There is comparably little information surrounding CML progression in veterinary species, including Yucatan miniature swine that are common for preclinical pharmaceutical and device testing. In humans, more than 90% of CML cases are associated with a chromosomal translocation that results in the Philadelphia gene (BCR/ABL mutation). In this report, the presence of the Philadelphia gene in a Yucatan burrow was confirmed in white blood cells collected prior to onset of clinical signs with primers designed from the human BCR/ABL sequence. Case Presentation: A 24 month old, 70 kg, Yucatan barrow received a prefabricated bovine cortical bone xenograft following a unilateral zygomatic ostectomy for a preclinical study. Complete blood count and serum chemistries were performed prior to and 28, 53, 106, and 129 days after facial surgery. Fifty three days after surgery, a bone marrow biopsy was performed due to anorexia, severe basophilia, and mild anemia. A finding of a moderate increase in basophilic precursors in bone marrow cytology was followed by lymphocyte immunophenotyping via flow cytometry and RT-PCR amplification of the Philadelphia gene in white blood cell samples from the affected barrow and an unaffected barrow in the same treatment group. Bone marrow, lymph node, liver, spleen, lung, kidney, and adrenal gland lesions of mostly myeloblasts were identified after the affected barrow died 146 days after surgery. Flow cytometry confirmed lymphopenia and suggested basophilia, and RT-PCR established the presence of the BCR/ABL gene. Conclusions: The information in this report confirms the presence of the BCR/ABL mutation and documents progression of chronic myelogenous (basophilic) leukemia from a chronic phase to a terminal blast crisis in an adult Yucatan barrow. The natural occurrence and progression of CML associated with the BCR/ABL mutation in miniature swine establishes potential for future porcine models of human CML. The information also establishes a genetic test to confirm porcine CML to prevent inadvertent attribution of clinical signs to treatment complications during preclinical testing.

Tissue engineered autologous cartilage-bone grafts for temporomandibular joint regeneration.

Joint disorders can be detrimental to quality of life. There is an unmet need for precise functional reconstruction of native-like cartilage and bone tissues in the craniofacial space and particularly for the temporomandibular joint (TMJ). Current surgical methods suffer from lack of precision and comorbidities and frequently involve multiple operations. Studies have sought to improve craniofacial bone grafts without addressing the cartilage, which is essential to TMJ function. For the human-sized TMJ in the Yucatan minipig model, we engineered autologous, biologically, and anatomically matched cartilage-bone grafts for repairing the ramus-condyle unit (RCU), a geometrically intricate structure subjected to complex loading forces. Using image-guided micromilling, anatomically precise scaffolds were created from decellularized bone matrix and infused with autologous adipose-derived chondrogenic and osteogenic progenitor cells. The resulting constructs were cultured in a dual perfusion bioreactor for 5 weeks before implantation. Six months after implantation, the bioengineered RCUs maintained their predefined anatomical structure and regenerated full-thickness, stratified, and mechanically robust cartilage over the underlying bone, to a greater extent than either autologous bone-only engineered grafts or acellular scaffolds. Tracking of implanted cells and parallel bioreactor studies enabled additional insights into the progression of cartilage and bone regeneration. This study demonstrates the feasibility of TMJ regeneration using anatomically precise, autologous, living cartilage-bone grafts for functional, personalized total joint replacement. Inclusion of the adjacent tissues such as soft connective tissues and the TMJ disc could further extend the functional integration of engineered RCUs with the host.

Agmatine for Pain Management in Dogs With Coxofemoral Joint Osteoarthritis: A Pilot Study.

Background: Pain from coxofemoral joint (CFJ) osteoarthritis (OA) characteristic of canine hip dysplasia (CHD) afflicts many dogs. Intervertebral disc (IVD) degeneration is a common CFJ OA comorbidity. Non-steroidal anti-inflammatory drug (NSAID) administration is standard for treatment of pain from degenerative joint disease. Potential side effects and tolerance from prolonged administration drive efforts to identify compounds that may be alternatives to or combined with NSAIDs. Agmatine, decarboxylated arginine, reportedly alleviates neuropathic pain, a likely component of OA pain. The objective of this study was to compare treatment response to agmatine and carprofen in dogs with varying degrees of CFJ OA with or without IVD degeneration and to test the hypothesis that agmatine improves hindlimb use comparably to carprofen and more than placebo. Methods: Nine hound-type dogs received oral carprofen (4.4 mg/kg, sid) for 7 days. Six months later, oral agmatine sulfate (25 mg/kg, bid) or placebo (hydroxypropyl methylcellulose, bid) was administered to the same dogs for 28 days with a 2 week washout period between treatments. Validated pain assessment scores were measured before treatment and every seven days throughout the treatment periods. Serum chemistry levels and ground reaction forces (GRF) were quantified before and after each treatment period. A board-certified radiologist quantified radiographic CFJ OA based on Orthopedic Foundation for Animals criteria and IVD degeneration on magnetic resonance images. GRFs were compared among treatments at each time point and among time points for each treatment. Results: There were no detectable adverse effects with any treatment. Significant results included improved GRFs in dogs with mild CFJ OA (N = 3) following agmatine administration compared to carprofen or placebo and a trend for improved GRFs in dogs with moderate CFJ OA (N = 2) following carprofen vs. agmatine or placebo. Neither agmatine nor carprofen improved GRFs in dogs with severe CFJ OA (N = 4). The GRFs improved in dogs with IVD degeneration (N = 3) following carprofen treatment compared to agmatine or placebo regardless of CFJ OA score, but no effect was observed in dogs with normal lumbar spines (N = 6). Conclusions: Results support agmatine over carprofen treatment to improve limb use in dogs with early or mild CFJ OA, while carprofen may be the better choice for dogs with moderate CFJ OA or IVD degeneration regardless of CFJ OA severity.

Traumatic neuroma of the anus after Milligan-Morgan hemorrhoidectomy.

There are several clinical settings of traumatic neuroma and a few may occur following surgical procedures. A 42-year-old man presented with anal pain five years after a Milligan Morgan hemorrhoidectomy for prolapsing hemorrhoids. A 4×4×3 mm sized anal polyp was seen during a rectal examination at a follow-up five years after surgery. The patient complained of point tenderness, pruritus, and anal discomfort as well as fecal retention. An endoscopy revealed a rectal polyp. Remarkably, histopathological examination and immunohistochemistry of the excised polyp showed a polypoid traumatic neuroma of the rectal plexus. After the excision of the polyp, the patient's complaint resolved completely. Traumatic neuromas may be a cause of significant pain and tenderness in patients with anal surgery or repair of anal lacerations. Interestingly, this is the second case of anal traumatic neuroma since Dr. Marks' first case in 1956 and is a possible complication of Milligan Morgan hemorrhoidectomy for prolapsing hemorrhoids. Similar complications of rectal surgery are reviewed.