Repair of critical size defects in the rat cranium using ceramic-reinforced PLA scaffolds obtained by supercritical gas foaming

Bioresorbable scaffolds made Of poly(L-lactic acid) (PLA) obtained by supercritical gas foaming were recently described as suitable for tissue engineering, portraying biocompatibility with primary osteoblasts in vitro and interesting mechanical properties when reinforced with ceramics. The behavior of such constructs remained to be evaluated in vivo and therefore the present study was undertaken to compare different PLA/ceramic composite scaffolds obtained by supercritical gas foaming in a critical size defect craniotomy model in Sprague-Dawley rats. The host-tissue reaction to the implants was evaluated semiquantitatively and similar tendencies were noted for all graft substitutes: initially highly reactive but decreasing with time implanted. Complete bone-bridging was observed IS weeks after implantation with PLA/ 5 wt % beta-TCP (PLA/TCP) and PLA/5 wt % HA (PLA/HA) scaffolds as assessed by histology and radiography. We show here for the first time that this solvent-free technique provides a promising approach in tissue engineering demonstrating both the biocompatibility and osteoconcluctivity of the processed structures in vivo

Electrospun PLLA Nanofiber Scaffolds and Their Use in Combination with BMP-2 for Reconstruction of Bone Defects

Introduction Adequate migration and differentiation of mesenchymal stem cells is essential for regeneration of large bone defects. To achieve this, modern graft materials are becoming increasingly important. Among them, electrospun nanofiber scaffolds are a promising approach, because of their high physical porosity and potential to mimic the extracellular matrix (ECM). Materials and Methods The objective of the present study was to examine the impact of electrospun PLLA nanofiber scaffolds on bone formation in vivo, using a critical size rat calvarial defect model. In addition we analyzed whether direct incorporation of bone morphogenetic protein 2 (BMP-2) into nanofibers could enhance the osteoinductivity of the scaffolds. Two critical size calvarial defects (5 mm) were created in the parietal bones of adult male Sprague-Dawley rats. Defects were either (1) left unfilled, or treated with (2) bovine spongiosa, (3) PLLA scaffolds alone or (4) PLLA/BMP-2 scaffolds. Cranial CT-scans were taken at fixed intervals in vivo. Specimens obtained after euthanasia were processed for histology, histomorphometry and immunostaining (Osteocalcin, BMP-2 and Smad5). Results PLLA scaffolds were well colonized with cells after implantation, but only showed marginal ossification. PLLA/BMP-2 scaffolds showed much better bone regeneration and several ossification foci were observed throughout the defect. PLLA/BMP-2 scaffolds also stimulated significantly faster bone regeneration during the first eight weeks compared to bovine spongiosa. However, no significant differences between these two scaffolds could be observed after twelve weeks. Expression of osteogenic marker proteins in PLLA/BMP-2 scaffolds continuously increased throughout the observation period. After twelve weeks osteocalcin, BMP-2 and Smad5 were all significantly higher in the PLLA/BMP-2 group than in all other groups. Conclusion Electrospun PLLA nanofibers facilitate colonization of bone defects, while their use in combination with BMP-2 also increases bone regeneration in vivo and thus combines osteoconductivity of the scaffold with the ability to maintain an adequate osteogenic stimulus

Wound dressings for a proteolytic-rich environment

Wound dressings have experienced continuous and significant changes over the years based on the knowledge of the biochemical events associated with chronic wounds. The development goes from natural materials used to just cover and conceal the wound to interactive materials that can facilitate the healing process, addressing specific issues in non-healing wounds. These new types of dressings often relate with the proteolytic wound environment and the bacteria load to enhance the healing. Recently, the wound dressing research is focusing on the replacement of synthetic polymers by natural protein materials to delivery bioactive agents to the wounds. This article provides an overview on the novel protein-based wound dressings such as silk fibroin keratin and elastin. The improved properties of these dressings, like the release of antibiotics and growth factors, are discussed. The different types of wounds and the effective parameters of healing process will be reviewed

Nonoperative Damage Control: The Use of Extracorporeal Membrane Oxygenation in Traumatic Bronchial Avulsion as a Bridge to Definitive Operation

The conventional treatment for an avulsed bronchus is emergent thoracotomy and repair or lobectomy. The principles of damage control thoracic operations include initial hemorrhage control with delayed definite repair after physiologic resuscitation. We report a multiply injured patient with avulsion of the left lower lobe bronchus. Profound acidosis, hypercarbia, and hypoxia precluded an emergent operation, and venovenous extracorporeal membrane oxygenation (V-V ECMO) was used for organ support during physiologic resuscitation. After the achievement of physiologic repletion, a thoracotomy and lobectomy were performed while the patient was supported by V-V ECMO

PADUA score as a predictor for pulmonary embolism: a potential strategy for reducing unnecessary imaging

An objective tool that is easy to integrate with an electronic medical record may help reduce unnecessary imaging for diagnosing a pulmonary embolism (PE). In this study, we assess the PADUA score in stratifying patients based on their risk of a PE. We reviewed charts of patients that underwent a computed tomography pulmonary angiogram (CT-PA) between January 2014 and September 2015 at our institution. Patient demographics including gender, age, race, and variables of the PADUA score were collected. The primary outcome was a positive CT-PA for a PE. Univariate and multivariate analysis was performed to derive predictors for a positive CT-PA. A receiver operator curve was calculated for the PADUA score and an optimal cutoff was calculated. Diagnostic test statistics were performed. Our study included 1067 patients. Of these, 185 (17.3%) had a PE. These patients tended to be older (64.3 SD 15.9 vs. 59.7 years SD 17.4, p \u3c 0.01), have a higher proportion of Black patients (38.9% vs. 31.9%, p = 0.03), have a higher median [IQR] PADUA score (4.0 [3-6] vs. 3.0 [1-4], p \u3c 0.01), and a higher rate of a DVT/PE history (30.3% vs. 5.2%, p \u3c 0.01). Independent predictors included a DVT/PE history (OR: 7.65, 95% CI 4.89-12.0, p \u3c 0.01), limited mobility (OR: 1.47, 95% CI 1.01-2.14, p = 0.046), and age 70 or greater (OR: 1.47, 95% CI 1.03-2.11, p = 0.03). The PADUA score had an AUC of 0.64 (95% CI 0.60-0.69, p = 0.046). The optimal cutoff was 4 and the sensitivity and specificity were 57.3% and 66.8%, respectively. The positive predictive and negative predictive values were 22.6% and 88.2%, respectively. The PADUA is a possible tool to stratify patients prior to performing a CT-PA. By using the score to guide management, we may be able to reduce unnecessary imaging through the implementation of the score in an EMR system. Further prospective research is warranted

In vivo targeting of dendritic cells in lymph nodes with poly(propylene sulfide) nanoparticles

Delivery of biodegradable nanoparticles to antigen-presenting cells (APCs), specifically dendritic cells (DCs), has potential for immunotherapy. This study investigates the delivery of 20, 45, and 100nm diameter poly(ethylene glycol)-stabilized poly(propylene sulfide) (PPS) nanoparticles to DCs in the lymph nodes. These nanoparticles consist of a cross-linked rubbery core of PPS surrounded by a hydrophilic corona of poly(ethylene glycol). The PPS domain is capable of carrying hydrophobic drugs and degrades within oxidative environments. 20 nm particles were most readily taken up into lymphatics following interstitial injection, while both 20 and 45nm nanoparticles showed significant retention in lymph nodes, displaying a consistent and strong presence at 24, 72, 96 and 120h post-injection. Nanoparticles were internalized by up to 40-50% of lymph node DCs (and APCs) without the use of a targeting ligand, and the site of internalization was in the lymph nodes rather than at the injection site. Finally, an increase in nanoparticle-containing DCs (and other APCs) was seen at 96h vs. 24h, suggesting an infiltration of these cells to lymph nodes. Thus, PPS nanoparticles of 20-45nm have the potential for immunotherapeutic applications that specifically target DCs in lymph node

PADUA score as a predictor for pulmonary embolism: a potential strategy for reducing unnecessary imaging

An objective tool that is easy to integrate with an electronic medical record may help reduce unnecessary imaging for diagnosing a pulmonary embolism (PE). In this study, we assess the PADUA score in stratifying patients based on their risk of a PE. We reviewed charts of patients that underwent a computed tomography pulmonary angiogram (CT-PA) between January 2014 and September 2015 at our institution. Patient demographics including gender, age, race, and variables of the PADUA score were collected. The primary outcome was a positive CT-PA for a PE. Univariate and multivariate analysis was performed to derive predictors for a positive CT-PA. A receiver operator curve was calculated for the PADUA score and an optimal cutoff was calculated. Diagnostic test statistics were performed. Our study included 1067 patients. Of these, 185 (17.3%) had a PE. These patients tended to be older (64.3 SD 15.9 vs. 59.7 years SD 17.4, p \u3c 0.01), have a higher proportion of Black patients (38.9% vs. 31.9%, p = 0.03), have a higher median [IQR] PADUA score (4.0 [3-6] vs. 3.0 [1-4], p \u3c 0.01), and a higher rate of a DVT/PE history (30.3% vs. 5.2%, p \u3c 0.01). Independent predictors included a DVT/PE history (OR: 7.65, 95% CI 4.89-12.0, p \u3c 0.01), limited mobility (OR: 1.47, 95% CI 1.01-2.14, p = 0.046), and age 70 or greater (OR: 1.47, 95% CI 1.03-2.11, p = 0.03). The PADUA score had an AUC of 0.64 (95% CI 0.60-0.69, p = 0.046). The optimal cutoff was 4 and the sensitivity and specificity were 57.3% and 66.8%, respectively. The positive predictive and negative predictive values were 22.6% and 88.2%, respectively. The PADUA is a possible tool to stratify patients prior to performing a CT-PA. By using the score to guide management, we may be able to reduce unnecessary imaging through the implementation of the score in an EMR system. Further prospective research is warranted