Facial deformities require precise reconstruction of the appearance and function of the original tissue. The current standard of care—the use of bone harvested from another region in the body—has major limitations, including pain and comorbidities associated with surgery. We have engineered one of the most geometrically complex facial bones by using autologous stromal/stem cells, without bone morphogenic proteins, using native bovine bone matrix and a perfusion bioreactor for the growth and transport of living grafts. The ramus-condyle unit (RCU), the most eminent load-bearing bone in the skull, was reconstructed using an image-guided personalized approach in skeletally mature Yucatan minipigs (human-scale preclinical model). We used clinically approved decellularized bovine trabecular bone as a scaffolding material, and crafted it into an anatomically correct shape using image-guided micromilling, to fit the defect. Autologous adipose-derived stromal/stem cells were seeded into the scaffold and cultured in perfusion for 3 weeks in a specialized bioreactor to form immature bone tissue. Six months after implantation, the engineered grafts maintained their anatomical structure, integrated with native tissues, and generated greater volume of new bone and greater vascular infiltration than either non-seeded anatomical scaffolds or untreated defects. This translational study demonstrates feasibility of facial bone reconstruction using autologous, anatomically shaped, living grafts formed in vitro, and presents a platform for personalized bone tissue engineering.
BackgroundStrains of Dirofilaria immitis suspected of lack of efficacy (LOE) to macrocyclic lactone (ML) preventive drugs have been increasingly reported in dogs by practicing veterinarians since 2005 in the Lower Mississippi Delta region. If proven, and not controlled in the early stages, the emergence of ML drug resistance threatens to become a widespread problem in the US that may limit the effectiveness of current preventive drug treatment methods.MethodsTo validate practice reports, a statewide survey of Louisiana veterinarians was done to define the extent of the problem and identify focal ‘hotspots’ of reported ML LOEs using Geographic Information Systems (GIS) methods. The present study then utilized microfilariae (Mf) from two canine field cases from different state locations that fit criteria for a high index of suspicion of LOE against heartworms by ML drugs. Blood containing Mf from the canine field cases was used to infect and produce L3 in Aedes aegypti for experimental infection of two groups of dogs, each of which contained two laboratory dogs, one treated with prophylactic ivermectin (12 μg/kg) monthly for 6 months at twice the label dose (6 μg/kg), and one untreated control.ResultsBoth treated and untreated dogs from Group I and Group II developed patent D. immitis infections by 218 DPI and 189 DPI, respectively, as evidenced by a positive occult heartworm antigen test and microfilaremia by the Knott’s test. Mf counts gradually increased post-patency in test and control dogs. Infective larvae raised from microfilariae from the treated Group I dog were used to successfully establish a second generation isolate, confirming heritability of resistance in the face of a monthly ivermectin challenge dose of 24 μg/kg, given monthly for 3 months.ConclusionsThese experimental infection studies provide in vivo evidence of the existence of ML drug resistance in dogs infected by D. immitis L3 from suspect field LOE cases in the Lower Mississippi Delta. Results encourage further work on mechanisms underlying the emergence of ML resistance in D. immitis and development of evidence-based resistance management strategies for heartworm preventives in order to extend the useful life of current drugs.
Background: Strains of Dirofilaria immitis suspected of lack of efficacy (LOE) to macrocyclic lactone (ML) preventive drugs have been increasingly reported in dogs by practicing veterinarians since 2005 in the Lower Mississippi Delta region. If proven, and not controlled in the early stages, the emergence of ML drug resistance threatens to become a widespread problem in the US that may limit the effectiveness of current preventive drug treatment methods.
Stem cell-based tissue regeneration offers potential for treatment of craniofacial bone defects. The dental follicle (DF), a loose connective tissue surrounding unerupted tooth, has been shown to contain progenitor/stem cells. Dental follicle stem cells (DFSCs) possess strong osteogenesis capability, which makes them suitable for repairing skeletal defects. The objective of this study was to evaluate bone regeneration capability of DFSCs loaded into polycaprolactone (PCL) scaffold for treatment of craniofacial defects. DFSCs were isolated from the first mandibular molars of postnatal Sprague Dawley rats and seeded into PCL scaffold. Cell attachment and cell viability on the scaffold were examined using scanning electron microscopy (SEM) and Alamar blue reduction assay. For in vivo transplantation, critical-size defects (CSD) were created on the skulls of 5 month-old immunocompetent rats, and the cell–scaffold constructs were transplanted into the defects. Skulls were collected at 4 and 8 weeks post-transplantation, and bone regeneration in the defects was evaluated with micro-CT and histological analysis. SEM and Alamar blue assay demonstrated attachment and proliferation of DFSCs in the PCL scaffold. Bone regeneration was observed in the defects treated with DFSC transplantation, but not in the controls without DFSC transplant. Transplanting DFSC-PCL with or without osteogenic induction prior to transplantation achieved approximately 50% bone regeneration at 8 weeks. Formation of woven bone was observed in the DFSC-PCL treatment group. Similar results were seen when osteogenic-induced DFSC-PCL was transplanted to the CSD. This study demonstrated that transplantation of DFSCs seeded into PCL scaffolds can be used to repair craniofacial defects.
Purpose/Aim The primary objective was to evaluate the effect of a bupivacaine mandibular nerve block on intraoperative blood pressure (BP) and heart rate (HR) in response to surgical stimulation and the need for systemic analgesics postoperatively. We hypothesized that a mandibular nerve block would decrease the need for systemic analgesics both intraoperatively and postoperatively. Materials and Methods Fourteen adult male Yucatan pigs were purchased. Pigs were chemically restrained with ketamine, midazolam, and dexmedetomidine and anesthesia was maintained with isoflurane inhalant anesthesia. Pigs were randomized to receive a mandibular block with either bupivacaine (bupivacaine group) or saline (control group). A nerve stimulator was used for administration of the block with observation of masseter muscle twitch to indicate the injection site. Invasive BP and HR were measured with the aid of an arterial catheter in eight pigs. A rescue analgesic protocol consisting of fentanyl and lidocaine was administered if HR or BP values increased 20% from baseline. Postoperative pain was quantified with a customized ethogram. HR and BP were evaluated at base line, pre-rescue, 10 and 20 min post-rescue. Results Pre-rescue mean BP was significantly increased (p = .001) for the bupivacaine group. Mean intraoperative HR was significantly lower (p = .044) in the bupivacaine versus saline group. All other parameters were not significant. Conclusion Addition of a mandibular nerve block to the anesthetic regimen in the miniature pig condylectomy model may improve variations in intraoperative BP and HR. This study establishes the foundation for future studies with larger animal numbers to confirm these preliminary findings.
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