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

Clostridium Difficile-Associated Infection in Trauma Patients: Development of the Clostridium Difficile Influencing Factors (CDIF) Score

CONTEXT: Clostridium difficile-associated infection (CDAI) can result in longer hospitalization, increased morbidity, and higher mortality rates for surgical patients. The impact on trauma patients is unknown, however. OBJECTIVE: To assess the effect of CDAI on trauma patients and develop a scoring system to predict CDAI in that population. METHODS: Records of all trauma patients admitted to a Level I Trauma Center from 2001 to 2014 were retrospectively reviewed. Presence of CDAI was defined as evidence of positive toxin or polymerase chain reaction. Patients with CDAI were matched to patients without CDAI using propensity score matching on a ratio of 1:3. MAIN OUTCOME MEASURES: Primary outcome was inhospital mortality. Secondary outcomes included length of stay and need for mechanical ventilation. A decision-tree analysis was performed to develop a predicting model for CDAI in the study population. RESULTS: During the study period, 11,016 patients were identified. Of these, 50 patients with CDAI were matched to 150 patients without CDAI. There were no differences in admission characteristics and demographics. Patients in whom CDAI developed had significantly higher mortality (12% vs 4%, p \u3c 0.01), need for mechanical ventilation (57% vs 23%, p \u3c 0.01), and mean hospital length of stay (15.3 [standard deviation 1.4]) days vs 2.1 [0.6] days, p \u3c 0.0). CONCLUSION: In trauma patients, CDAI results in significant morbidity and mortality. The C difficile influencing factor score is a useful tool in identifying patients at increased risk of CDAI

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

Bone repair with a form of BMP-2 engineered for incorporation into fibrin cell ingrowth matrices.

Most growth factors naturally involved in development and regeneration demonstrate strong binding to the extracellular matrix and are retained there until being locally mobilized by cells. In spite of this feedback between cell activity and growth factor mobilization in the extracellular matrix, this approach has not been extensively explored in therapeutic situations. We present an engineered bone morphogenetic protein-2 (BMP-2) fusion protein that mimics such function in a surgically relevant matrix, fibrin, incorporated into the matrix until it is locally liberated by cell surface-associated proteases. A tripartite fusion protein, denoted TG-pl-BMP-2, was designed and produced recombinantly. An N-terminal transglutaminase substrate (TG) domain provides covalent attachment to fibrin during coagulation under the influence of the blood transglutaminase factor XIIIa. A central plasmin substrate (pl) domain provides a cleavage site for local release of the attached growth factor from the fibrin matrix under the influence of cell-activated plasmin. A C-terminal human BMP-2 domain provides osteogenic activity. TG-pl-BMP-2 in fibrin was evaluated in vivo in critical-size craniotomy defects in rats, where it induced 76% more defect healing with bone at 3 weeks with a dose of 1 mug/defect than wildtype BMP-2 in fibrin. After a dosing study in rabbits, the engineered growth factor in fibrin was evaluated in a prospective clinical study for pancarpal fusion in dogs, where it induced statistically faster and more extensive bone bridging than equivalent treatment with cancellous bone autograft. The strong healing response shown by fibrin including a bound BMP-2 variant suggests that with the combination of bound growth factor and ingrowth matrix, it may be possible to improve upon the natural growth factor and even upon tissue autograft

Psoas Muscle Area Predicts Acute Respiratory Distress Syndrome in Acute Pancreatitis

Introduction: Acute Respiratory Distress Syndrome (ARDS) is a serious complication of acute pancreatitis. However, limited literature exists pertaining to patient characteristics that can help predict the development of ARDS among patients with acute pancreatitis. Sarcopenia, based on psoas muscle area on imaging, has been predictive of outcomes after surgery. We hypothesized that sarcopenia would correlate with development of ARDS in patients admitted for acute pancreatitis. Methods: We performed a retrospective study of patients that were admitted to the ICU for acute pancreatitis at our institution. Patients that did not have a CT of their abdomen were excluded from the study. Patient characteristics including demographics, medical history, BMI, labs at admission, and functional status were collected. An average psoas muscle area for each patient was calculated at the level of L3 and standardized to their height. Sarcopenia was determined by gender-based cutoffs of the psoas areas. We then performed both univariate and multivariate analysis to determine significant covariates in the development of ARDS. Results: We included 218 patients in the study. Of these patients, 32 (14.7%) developed ARDS. In univariate analysis, there was no significant difference in the proportion of patients with ARDS that were sarcopenic (50.0% vs 35.7%, p = 0.12). The mean age was significantly higher in those that developed ARDS (58.0 vs 47.3, p\u3c0.01). There was no difference in gender (59.4% male vs 55.9%, p = 0.72), mean BMI (30.1 vs 29.1, p = 0.52), mean albumin (2.71 vs 2.85, p = 0.48), and mean serum creatinine (2.01 vs 1.52, p = 0.14). Patients with ARDS had a higher proportion of biliary etiology (38.7% vs 14.9%, p \u3c 0.01), history of coronary artery disease (21.9% vs 11.4%, p = 0.01) and COPD (25.0% vs 10.3%, p = 0.02). Patients that developed ARDS also had a lower proportion of independent patients (54.2% vs 80.9%, p\u3c0.01). In multivariate analysis, the only significant predictors for ARDS were the presence of sarcopenia (OR = 5.15, 95% CI: 1.23-21.49) and a history of COPD (OR = 6.60, 95% CI: 1.46-29.96). Conclusion: In our single institute retrospective study, we have found a significant relationship between the presence of sarcopenia based on psoas muscle area and the development of ARDS. Further research on utilizing this simple measurement to risk-stratify patients with acute pancreatitis is warranted.https://scholarlycommons.henryford.com/merf2019clinres/1017/thumbnail.jp