Development of a modular, biocompatible thiolated gelatin microparticle platform for drug delivery and tissue engineering applications

The field of biomaterials has advanced significantly in the past decade. With the growing need for high-throughput manufacturing and screening, the need for modular materials that enable streamlined fabrication and analysis of tissue engineering and drug delivery schema has emerged. Microparticles are a powerful platform that have demonstrated promise in enabling these technologies without the need to modify a bulk scaffold. This building block paradigm of using microparticles within larger scaffolds to control cell ratios, growth factors and drug release holds promise. Gelatin microparticles (GMPs) are a well-established platform for cell, drug and growth factor delivery. One of the challenges in using GMPs though is the limited ability to modify the gelatin post-fabrication. In the present work, we hypothesized that by thiolating gelatin before microparticle formation, a versatile platform would be created that preserves the cytocompatibility of gelatin, while enabling post-fabrication modification. The thiols were not found to significantly impact the physicochemical properties of the microparticles. Moreover, the thiolated GMPs were demonstrated to be a biocompatible and robust platform for mesenchymal stem cell attachment. Additionally, the thiolated particles were able to be covalently modified with a maleimide-bearing fluorescent dye and a peptide, demonstrating their promise as a modular platform for tissue engineering and drug delivery applications.

Association between Urinary Phthalate Metabolites and Markers of Endothelial Dysfunction in Adolescents and Young Adults

Endothelial function is crucial in the pathogenesis of circulatory and cardiovascular toxicity; epidemiologic research investigating the association between phthalate exposure and endothelial dysfunction remains limited. We examined the associations between exposures to specific phthalates (di-2-ethylhexyl phthalate, DEHP; di-n-butyl phthalate, DnBP) and circulating endothelial and platelet microparticles (EMPs and PMPs) in adolescents and young adults. Of the 697 participants recruited, anthropometric measurements and health-related behaviors relevant to cardiovascular risks were collected and assessed. Urine and serum were collected and analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and flow cytometry. Multiple linear regression indicated that increases in urinary concentrations of ΣDEHP and MnBP (mono-n-butyl phthalate), across quartiles, were positively associated with serum EMPs level (p for trend <0.001 and <0.001; β = 0.798 and 0.007; standard error = 0.189 and 0.001, respectively). Moreover, female and overweight subjects had higher MnBP, and males were more vulnerable to DnBP exposure compared to females. In conclusion, our results demonstrate a dose-response relationship between exposures to phthalates (ΣDEHP and MnBP) and microparticle formation (EMPs and PMPs) in adolescents and young adults. The findings indicate that exposures to phthalates of both low and high-molecular weight are positively associated with microparticle production, and might contribute to endothelial dysfunction; such damage might manifest in the form of atherosclerotic-related vascular diseases. Future in vivo and in vitro studies are warranted to elucidate whether a causal relationship exists between phthalate exposure and EMPs and PMPs.

Device-Induced Hemostatic Disorders in Mechanically Assisted Circulation

Mechanically assisted circulation (MAC) sustains the blood circulation in the body of a patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) or on ventricular assistance with a ventricular assist device (VAD) or on extracorporeal membrane oxygenation (ECMO) with a pump-oxygenator system. While MAC provides short-term (days to weeks) support and long-term (months to years) for the heart and/or lungs, the blood is inevitably exposed to non-physiological shear stress (NPSS) due to mechanical pumping action and in contact with artificial surfaces. NPSS is well known to cause blood damage and functional alterations of blood cells. In this review, we discussed shear-induced platelet adhesion, platelet aggregation, platelet receptor shedding, and platelet apoptosis, shear-induced acquired von Willebrand syndrome (AVWS), shear-induced hemolysis and microparticle formation during MAC. These alterations are associated with perioperative bleeding and thrombotic events, morbidity and mortality, and quality of life in MCS patients. Understanding the mechanism of shear-induce hemostatic disorders will help us develop low-shear-stress devices and select more effective treatments for better clinical outcomes.

Cross-linked coacervates of cashew gum and gelatin in the encapsulation of pequi oil

ABSTRACT: Pequi oil is rich in bioactive compounds which can be encapsulated to increase protection against extrinsic environmental factors. A delayed degradation of pequi oil may occur by using microencapsulation technology, in addition to masking unpleasant flavors and aromas. Complex coacervation is a technique based on the electrostatic interaction between two oppositely charged biopolymers which form a matrix complexed around an agent of interest. However, cross-linking the particles is often necessary in order to make them more rigid. The objective of this research was to produce and characterize pequi oil microparticles in a cashew gum (CG) and gelatin (GE) matrix cross-linked with tannic acid. Cross-linked pequi oil microparticles were produced by varying the concentrations of biopolymers (0.5% to 1.5%) and tannic acid (0.3% to 8.1%) using a rotational central compound design. Ratio of cashew gum, gelatin and oil was 2:1:1 (m/m/m);respectively, at pH 4.5. The cross-linking process was performed with tannic acid for 30 minutes at 40 °C. The optimized formulation by means of the rotational central compound design for microparticle formation was 0.65% biopolymers (CG and GE) and 6.9% tannic acid. Increasing the tannic acid percentage in the cross-linking of the pequi oil particles had a higher yield and encapsulation efficiency. Cross-linking provided an increase in the degradation temperature of material; and consequently, improved the thermal stability of the particles. The cross-linking process was advantageous in producing the microparticles.