Ketorolac is relatively COX-1 selective while bromfenac is potently selective for COX-2 over COX-1. In the animal model, both ketorolac 0.4% and bromfenac 0.09% demonstrated maximal anti-inflammatory activity in treated eyes. Only bromfenac 0.09% had a significant effect on the contralateral eye, suggesting possible systemic absorption of this drug.

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At least 26% of recent battlefield injuries are to the craniomaxillofacial (CMF) region. Recombinant human bone morphogenetic protein 2 (rhBMP‐2) is used to treat CMF open fractures, but several complications have been associated with its use. This study tested the efficacy and safety of a lower (30% recommended) dose of rhBMP‐2 to treat mandibular fractures. rhBMP‐2 delivered via a polyurethane (PUR) and hydroxyapatite/β‐tricalcium phosphate (Mastergraft®) scaffold was evaluated in a 2 cm segmental mandibular defect in minipigs. Bone regeneration was analyzed at 4, 8, and 12 weeks postsurgery using clinical computed tomography (CT) and rhBMP‐2, and inflammatory marker concentrations were analyzed in serum and surgery‐site drain effluent. CT scans revealed that pigs treated with PUR‐Mastergraft® + rhBMP‐2 had complete bone bridging, while the negative control group showed incomplete bone‐bridging (n = 6). Volumetric analysis of regenerated bone showed that the PUR‐Mastergraft® + rhBMP‐2 treatment generated significantly more bone than control by 4 weeks, a trend that continued through 12 weeks. Variations in inflammatory analytes were detected in drain effluent samples and saliva but not in serum, suggesting a localized healing response. Importantly, the rhBMP‐2 group did not exhibit an excessive increase in inflammatory analytes compared to control. Treatment with low‐dose rhBMP‐2 increases bone regeneration capacity in pigs with mandibular continuity defects and restores bone quality. Negative complications from rhBMP‐2, such as excessive inflammatory analyte levels, were not observed. Together, these results suggest that treatment with low‐dose rhBMP‐2 is efficacious and may improve safety when treating CMF open fractures. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1491–1503, 2019.

IntroductionSevere trauma is accompanied by a period of hypermetabolism and disuse. In this study, a rat model was used to determine the effects of burn and disuse independently and in combination on body composition, food intake and adipokines.MethodsMale rats were assigned to four groups 1) sham ambulatory (SA), 2) sham hindlimb unloaded (SH), 3) 40% total body surface area full thickness scald burn ambulatory (BA) and 4) burn and hindlimb unloaded (BH). Animals designated to the SH and BH groups were placed in a tail traction system and their hindlimbs unloaded. Animals were followed for 14 days. Plasma, urine, fecal and tissue samples were analyzed.ResultsSA had a progressive increase in body mass (BM), SH and BA no change and BH a reduction. Compared to SA, BM was reduced by 10% in both SH and BA and by 17% when combined in BH. Compared to SA, all groups had reductions in lean and fat body mass with BH being greater. The decrease in lean mass was associated with the rate of urinary corticosterone excretion. The loss in fat mass was associated with decreases in plasma leptin and adiponectin and an increase in ghrelin. Following the acute response to injury, BH had a greater food intake per 100 g BM. Food intake was associated with the levels of leptin, adiponectin and ghrelin.ConclusionsThe effects of the combination of burn and disuse in this animal model were additive, therefore in assessing metabolic changes with severe trauma both injury and disuse should be considered. Furthermore, the observed changes in adipokines, corticosterone and ghrelin provide insights for interventions to attenuate the hypermetabolic state following injury, possibly reducing catabolism and muscle loss and subsequent adverse effects on recovery and function.

Multiple assessment methods are available to evaluate the performance of engineered scaffolds in accepted bone healing animal models. Evaluation and comparison of these methods can aid in the planning of future animal studies, as well as, inform clinical assessments as the engineered scaffolds translate into clinical studies and applications. To evaluate multiple bone assessment techniques, bone regrowth potential of tyrosine-derived polycarbonate (TyrPC) scaffolds loaded with various dosages of recombinant human bone morphogenetic protein-2 (rhBMP-2) (0, 10, 25, and 50 μg) was assessed after 16 weeks in vivo in a rabbit calvarial model. Traditional X-ray radiography and micro-computed tomography (micro-CT) analyses were used to quantify the volume and density of regenerated bone. Histomorphometric analysis was performed as the traditional gold standard of evaluation. While these techniques are fairly standard in bone tissue engineering, we also investigated 64-slice CT, a tool more commonly used clinically, for comparison and to guide translational efforts. The 64-slice CT scans were carried out at 4 and 16 weeks to monitor temporal bone healing patterns. Study results indicated a clear dose-dependent response of increasing regenerated bone volume with rhBMP-2 loaded on the TyrPC scaffolds after 16 weeks of implantation. Significantly more bone formation was observed at the highest dose of rhBMP-2 (50 μg), which is 25-50% of the previously recommended dose (100-200 μg) for this defect. A significant difference was observed between the lowest and highest doses using radiographs (p<0.001), micro-CT (p=0.002), and CT (p<0.001) and a high correlation was found between techniques (R(2) values between 0.446 and 0.911). It was found that the number of animals required per group to detect significant dose effects ranged between 6 and 8 for the imaging methods while histomorphometric analysis would require 25 animals per group to detect similar differences (desired power=0.9, α=0.05). Radiographic analysis provided quantifiable % defect coverage and radio-opacity, micro-CT provided spatial volumetric and bone density measures, histomorphometry provided biological confirmation, and 64-slice CT allowed for establishing of clinically relevant translational guidelines. These methodologies allow for a standardized and comprehensive description of bone regeneration and provide guidelines for the planning of future preclinical and clinical studies.