Bone Morphogenetic Protein-2 Adsorption onto Poly-ɛ-caprolactone Better Preserves Bioactivity In Vitro and Produces More Bone In Vivo than Conjugation Under Clinically Relevant Loading Scenarios

Background: One strategy to reconstruct large bone defects is to prefabricate a vascularized flap by implanting a biomaterial scaffold with associated biologics into the latissimus dorsi and then transplanting this construct to the defect site after a maturation period. This strategy, similar to all clinically and regulatory feasible biologic approaches to surgical reconstruction, requires the ability to quickly (<1?h within an operating room) and efficiently bind biologics to scaffolds. It also requires the ability to localize biologic delivery. In this study, we investigated the efficacy of binding bone morphogenetic protein-2 (BMP2) to poly-?-caprolactone (PCL) using adsorption and conjugation as a function of time. Methods: BMP2 was adsorbed (Ads) or conjugated (Conj) to PCL scaffolds with the same three-dimensional printed architecture while altering exposure time (0.5, 1, 5, and 16?h), temperature (4°C, 23°C), and BMP2 concentration (1.4, 5, 20, and 65??g/mL). The in vitro release was quantified, and C2C12 cell alkaline phosphatase (ALP) expression was used to confirm bioactivity. Scaffolds with either 65 or 20??g/mL Ads or Conj BMP2 for 1?h at 23°C were implanted subcutaneously in mice to evaluate in vivo bone regeneration. Micro-computed tomography, compression testing, and histology were performed to characterize bone regeneration. Results: After 1?h exposure to 65??g/mL BMP2 at 23°C, Conj and Ads resulted in 12.83±1.78 and 10.78±1.49??g BMP2 attached, respectively. Adsorption resulted in a positive ALP response and had a small burst release; whereas conjugation provided a sustained release with negligible ALP production, indicating that the conjugated BMP2 may not be bioavailable. Adsorbed 65??g/mL BMP2 solution resulted in the greatest regenerated bone volume (15.0±3.0?mm3), elastic modulus (20.1±3.0?MPa), and %bone ingrowth in the scaffold interior (17.2%±5.4%) when compared with conjugation. Conclusion: Adsorption may be optimal for the clinical application of prefabricating bone flaps due to BMP2 binding in a short exposure time, retained BMP2 bioactivity, and bone growth adhering to scaffold geometry and into pores with healthy marrow development.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140249/1/ten.tec.2014.0377.pd

A comparative study between manual vacuum aspiration and electronic suction for surgical treatment of abortion

Background: Present study is done to study the safety, efficacy and complications of using manual vacuum aspiration (MVA) for surgical management of first trimester abortion in comparison to electronic suction.Methods: It is a retrospective observational study conducted in department of obstetrics and gynecology at tertiary care hospital. Out of 100 cases taken, 50 abortions were terminated by MVA and 50 were terminated by electric suction/vacuum aspiration (EVA).Results: In this study, majority of the patients were primigravida (60%). Most of the patients had period of gestation between 7 to 9 weeks (40%) followed by up to 6 weeks (33%) in both groups. Time taken for the procedure was less in MVA (5-9 min.) than electronic suction (7-11 min.). In terms of complications, blood loss ≥100 ml was more with EVA (18%) compared to MVA (6%). Uterine perforation was seen with EVA (4%) and none with MVA. As far as success rate is concerned, EVA got 98% while MVA got 90%. Post-operative hospital stay was less with MVA (≤12 hours) than EVA (up to 24 hours). Post-operative pain perception was less with MVA (18% severe pain) while with EVA, 36% with severe pain.Conclusions: Both the evacuation techniques are almost equally effective and safe, still duration; post-operative pain and hospital stay are less with MVA. Success rate is better with EVA

Dual Delivery of EPO and BMP2 from a Novel Modular Poly-ɛ-Caprolactone Construct to Increase the Bone Formation in Prefabricated Bone Flaps

Poly-?-caprolactone (PCL) is a biocompatible polymer that has mechanical properties suitable for bone tissue engineering; however, it must be integrated with biologics to stimulate bone formation. Bone morphogenetic protein-2 (BMP2) delivered from PCL produces bone when implanted subcutaneously, and erythropoietin (EPO) works synergistically with BMP2. In this study, EPO and BMP2 are adsorbed separately on two 3D-printed PCL scaffold modules that are assembled for codelivery on a single scaffold structure. This assembled modular PCL scaffold with dual BMP2 and EPO delivery was shown to increase bone growth in an ectopic location when compared with BMP2 delivery along a replicate scaffold structure. EPO (200?IU/mL) and BMP2 (65??g/mL) were adsorbed onto the outer and inner portions of a modular scaffold, respectively. Protein binding and release studies were first quantified. Subsequently, EPO+BMP2 and BMP2 scaffolds were implanted subcutaneously in mice for 4 and 8 weeks, and the regenerated bone was analyzed with microcomputed tomography and histology; 8.6±1.4??g BMP2 (22%) and 140±29?IU EPO (69.8%) bound to the scaffold and <1% BMP2 and 83% EPO was released in 7 days. Increased endothelial cell proliferation on EPO-adsorbed PCL discs indicated protein bioactivity. At 4 and 8 weeks, dual BMP2 and EPO delivery regenerated more bone (5.1±1.1 and 5.5±1.6?mm3) than BMP2 alone (3.8±1.1 and 4.3±1.7?mm3). BMP2 and EPO scaffolds had more ingrowth (1.4%±0.6%) in the outer module when compared with BMP2 (0.8%±0.3%) at 4 weeks. Dual delivery produced more dense cellular marrow, while BMP2 had more fatty marrow. Dual EPO and BMP2 delivery is a potential method to regenerate bone faster for prefabricated flaps.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140252/1/ten.tec.2014.0643.pd

School nurse asthma program reduces healthcare utilization in children with persistent asthma

OBJECTIVE: We examined the impact of a novel, school nurse-supervised asthma therapy program on healthcare utilization. METHODS: We retrospectively reviewed charts of 84 children enrolled in this program in central Massachusetts between 2012 and 2015. Physicians identified children with persistent asthma and poor medication adherence. These children were enrolled in the program to receive daily-inhaled corticosteroid at school, supervised by their school nurse, with ongoing communication between physician\u27s office and school nurse through the school year. This program relied on established family, provider and school resources rather than research staff. The primary outcome was change in the number of emergency department (ED) visits in the year before and after enrollment. Secondary outcomes were hospital admissions, school absences, and rescue medication use. RESULTS: The study population was on average 10.5 years old, 63% male, 67% Hispanic, 19% black, 14% white with 95% using Medicaid insurance. Asthma-related ED visits over a 1-year period decreased 37.5%, from a pre-intervention mean of 0.8 visits to a post-intervention mean of 0.3 visits (p \u3c 0.001). Asthma-related hospital admissions decreased from a pre-intervention mean of 0.3 admissions to post-intervention mean of 0 admissions (p \u3c 0.001). Asthma rescue medication refills decreased by 46.3% from the pre- to post-intervention period (p = \u3c .001). There were also non-significant declines in school absences and oral steroid use for children enrolled. CONCLUSIONS: We demonstrate a significant reduction in healthcare utilization for children enrolled in this unique school nurse-supervised asthma program, which utilizes a clinical-school partnership to deliver preventative asthma medication to school-aged children under sustainable conditions

Dual Delivery of EPO and BMP2 from a Novel Modular Poly-ɛ-Caprolactone Construct to Increase the Bone Formation in Prefabricated Bone Flaps

Poly-?-caprolactone (PCL) is a biocompatible polymer that has mechanical properties suitable for bone tissue engineering; however, it must be integrated with biologics to stimulate bone formation. Bone morphogenetic protein-2 (BMP2) delivered from PCL produces bone when implanted subcutaneously, and erythropoietin (EPO) works synergistically with BMP2. In this study, EPO and BMP2 are adsorbed separately on two 3D-printed PCL scaffold modules that are assembled for codelivery on a single scaffold structure. This assembled modular PCL scaffold with dual BMP2 and EPO delivery was shown to increase bone growth in an ectopic location when compared with BMP2 delivery along a replicate scaffold structure. EPO (200?IU/mL) and BMP2 (65??g/mL) were adsorbed onto the outer and inner portions of a modular scaffold, respectively. Protein binding and release studies were first quantified. Subsequently, EPO+BMP2 and BMP2 scaffolds were implanted subcutaneously in mice for 4 and 8 weeks, and the regenerated bone was analyzed with microcomputed tomography and histology; 8.6±1.4??g BMP2 (22%) and 140±29?IU EPO (69.8%) bound to the scaffold and <1% BMP2 and 83% EPO was released in 7 days. Increased endothelial cell proliferation on EPO-adsorbed PCL discs indicated protein bioactivity. At 4 and 8 weeks, dual BMP2 and EPO delivery regenerated more bone (5.1±1.1 and 5.5±1.6?mm3) than BMP2 alone (3.8±1.1 and 4.3±1.7?mm3). BMP2 and EPO scaffolds had more ingrowth (1.4%±0.6%) in the outer module when compared with BMP2 (0.8%±0.3%) at 4 weeks. Dual delivery produced more dense cellular marrow, while BMP2 had more fatty marrow. Dual EPO and BMP2 delivery is a potential method to regenerate bone faster for prefabricated flaps.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140252/1/ten.tec.2014.0643.pd

The role of PPARy in carbon nanotube-elicited granulomatous lung inflammation

"BACKGROUND: Although granulomatous inflammation is a central feature of many disease processes, cellular mechanisms of granuloma formation and persistence are poorly understood. Carbon nanoparticles, which can be products of manufacture or the environment, have been associated with granulomatous disease. This paper utilizes a previously described carbon nanoparticle granuloma model to address the issue of whether peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear transcription factor and negative regulator of inflammatory cytokines might play a role in granulomatous lung disease. PPARγ is constitutively expressed in alveolar macrophages from healthy individuals but is depressed in alveolar macrophages of patients with sarcoidosis, a prototypical granulomatous disease. Our previous study of macrophage-specific PPARγ KO mice had revealed an intrinsically inflammatory pulmonary environment with an elevated pro-inflammatory cytokines profile as compared to wild-type mice. Based on such observations we hypothesized that PPARγ expression would be repressed in alveolar macrophages from animals bearing granulomas induced by MWCNT instillation. METHODS: Wild-type C57Bl/6 and macrophage-specific PPARγ KO mice received oropharyngeal instillations of multiwall carbon nanotubes (MWCNT) (100 μg). Bronchoalveolar lavage (BAL) cells, BAL fluids, and lung tissues were obtained 60 days post-instillation for analysis of granuloma histology and pro-inflammatory cytokines (osteopontin, CCL2, and interferon gamma [IFN-γ] mRNA and protein expression. RESULTS: In wild-type mice, alveolar macrophage PPARγ expression and activity were significantly reduced in granuloma-bearing animals 60 days after MWCNT instillation. In macrophage-specific PPARγ KO mice, granuloma formation was more extensive than in wild-type at 60 days after MWCNT instillation. PPARγ KO mice also demonstrated elevated pro-inflammatory cytokine expression in lung tissue, laser-microdissected lung granulomas, and BAL cells/fluids, at 60 days post MWCNT exposure. CONCLUSIONS: Overall, data indicate that PPARγ deficiency promotes inflammation and granuloma formation, suggesting that PPARγ functions as a negative regulator of chronic granulomatous inflammation.

Management of oral and maxillofacial trauma during the first wave of the COVID-19 pandemic in the United Kingdom

We assess the effect of coronavirus disease 2019 (COVID-19) on UK oral and maxillofacial (OMF) trauma services and patient treatment during the first wave of the pandemic. From 1 April 2020 until 31 July 2020, OMF surgery units in the UK were invited to prospectively record all patients presenting with OMF trauma. Information included clinical presentation, mechanism of injury, how it was managed, and whether or not treatment included surgery. Participants were also asked to compare the patient’s care with the treatment that would normally have been given before the crisis. Twenty-nine units across the UK contributed with 2,229 entries. The most common aetiology was mechanical fall (39%). The most common injuries were soft tissue wounds (52%) and, for hard tissues, mandibular fractures (13%). Of 876 facial fractures, 79 patients’ treatment differed from what would have been normal pre-COVID, and 33 had their treatment deferred. Therefore the care of 112 (14%) patients was at variance with normal practice because of COVID restrictions. The pattern of OMFS injuries changed during the first COVID-19 lockdown. For the majority, best practice and delivery of quality trauma care continued despite the on-going operational challenges, and only a small proportion of patients had changes to their treatment. The lessons learnt from the first wave, combined with adequate resources and preoperative testing of patients, should allow those facial injuries in the second wave to receive best-practice care