There is a growing clinical need to address high failure rates of small diameter (< 6 mm) synthetic vascular grafts. Although there is a strong empirical correlation between low patency rates and low compliance of synthetic grafts, the mechanism by which compliance mismatch leads to intimal hyperplasia is poorly understood. To elucidate this relationship, synthetic vascular grafts were fabricated that varied compliance independent of other graft variables. A computational model was then used to estimate changes in fluid flow and wall shear stress as a function of graft compliance. The effect of compliance on arterial remodeling in an ex vivo organ culture model was then examined to identify early markers of intimal hyperplasia. The computational model prediction of low wall shear stress of low compliance grafts and clinical control correlated well with alterations in arterial smooth muscle cell marker, extracellular matrix, and inflammatory marker staining patterns at the distal anastomoses. Conversely, high compliance grafts displayed minimal changes in fluid flow and arterial remodeling, similar to the sham control. Overall, this work supports the intrinsic link between compliance mismatch and intimal hyperplasia and highlights the utility of this ex vivo organ culture model for rapid screening of small diameter vascular grafts.

Central nervous system (CNS) injuries persist for years, and currently there are no therapeutics that can address the complex injury cascade that develops over this time-scale. 17β-estradiol (E2) has broad tropism within the CNS, targeting and inducing beneficial phenotypic changes in myriad cells following injury. To address the unmet need for vastly prolonged E2 release, we report first-generation poly(pro-E2) biomaterial scaffolds that release E2 at nanomolar concentrations over the course of 1–10 years via slow hydrolysis in vitro. As a result of their finely tuned properties, these scaffolds demonstrate the ability to promote and guide neurite extension ex vivo and protect neurons from oxidative stress in vitro. The design and testing of these materials reported herein demonstrate the first step towards next-generation implantable biomaterials with prolonged release and excellent regenerative potential.

Nervous system damage caused by physical trauma or degenerative diseases can result in loss of sensory and motor function for patients. Biomaterial interventions have shown promise in animal studies, providing contact guidance for extending neurites or sustained release of various drugs and growth factors; however, these approaches often target only one aspect of the regeneration process. More recent studies investigate hybrid approaches, creating complex materials that can reduce inflammation or provide neuroprotection in addition to stimulating growth and regeneration. Magnetic materials have shown promise in this field, as they can be manipulated non-invasively, are easily functionalized, and can be used to mechanically stimulate cells. By combining different types of biomaterials (hydrogels, nanoparticles, electrospun fibers) and incorporating magnetic elements, magnetic materials can provide multiple physical and chemical cues to promote regeneration. This review, for the first time, will provide an overview of design strategies for promoting regeneration after neural injury with magnetic biomaterials.

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The development and maintenance of cocaine addiction depend heavily on learned reward-environment associations that can induce drug-seeking behavior and relapse. Understanding the mechanisms underlying these cue-induced conditioned responses is important for relapse prevention. To test whether intracellular responses measured after cocaine conditioned place preference (CPP) expression are context-dependent, we re-exposed cocaine-treated rats (drug-free) to an environment previously paired with cocaine or saline, 24 h after the CPP test. After 8 days of cocaine CPP training with one of two cocaine doses (5 mg/kg or 20 mg/kg, i.p.), CPP was expressed only after conditioning with the higher cocaine dose. In CPP expressing rats, locomotor responses after re-exposure to the cocaine-chamber were greater than in rats re-exposed to the saline-paired chamber. Nucleus Accumbens (NAc) phosphorylated ERK (pERK) levels were increased after re-exposure to the cocaine-paired, but not the saline-paired chamber, regardless of whether or not CPP behavior was expressed. Caudate Putamen (CPu) pERK and FosB protein levels increased after re-exposure to the cocaine chamber only after conditioning with the higher cocaine dose. Conversely, the higher cocaine dose, independent of environment, resulted in increased NAc FosB, ΔFosB and phosphorylated CREB (pCREB) protein levels compared to those conditioned with 5 mg/kg cocaine (non-CPP-expressing). Our results suggest that NAc ERK phosphorylation may be involved with retrieving the contextual information of a cocaine-association, without necessarily motivating the expression of CPP behavior. Additionally, we show distinct patterns of intracellular responses in the NAc and CPu indicating a region-specific role for pERK/pCREB/FosB intracellular signaling in the retrieval of cocaine-context associations.

The aim of this study was to investigate the intracellular responses associated with the acquisition and expression of cocaine-context associations. ERK (extracellular regulated kinase), CREB (cAMP responsive element binding protein), FosB and ΔFosB proteins were of particular interest due to their involvement in cocaine reward and in synaptic plasticity underlying learning and memory. We used the conditioned place preference (CPP) paradigm, which employs a Pavlovian conditioning procedure to establish an association between a drug-paired environment and the drug’s rewarding effects, to study the role of these signaling pathways in cocaine-context associations. N-methyl-D-aspartate receptor (NMDAR) antagonism prior to cocaine administration during conditioning blocked the acquisition of cocaine CPP and reduced Nucleus Accumbens (NAc) phosphorylated-ERK (pERK) and phosphorylated CREB (pCREB) levels following the CPP test (drug-free). We also show that cocaine-induced increases in Caudate Putamen (CPu) FosB and ΔFosB levels are decreased after MK-801 pre-treatment during conditioning. In addition, our results provide evidence for the involvement of striatal SIRT (Silent Information Regulator of Transcription) proteins in cocaine-CPP. These results will aid in the advancement of general knowledge about the molecular formation and retrieval of cocaine-associated memories that can be used in the future when designing treatments for cocaine addiction that target both prevention and relapse.

The hydrophobicity of electrospun poly-Llactic acid (PLLA) fibers hinders their integration with surrounding tissue for a variety of applications. In this study, we increased PLLA fiber hydrophilicity by incorporating the natural surfactant, lactonic sophorolipid (LSL). PLLA+LSL fibers had similar fiber morphology but significantly greater surface wettability, which suggested LSL accumulation on the fiber surface. Differential scanning calorimetry results also suggested that LSL was phase separated from PLLA. Despite the altered surface wettability of these fibers, there was no change in fibroblast adhesion. Future studies may explore the use of this natural surfactant to deliver bioactive factors to enhance fibroblast adhesion.

Achieving graft endothelialization following implantation continues to be a challenge in the development of “off-the-shelf,” small-caliber, arterial prostheses. Coating grafts with biomolecules to support the retention, migration, and differentiation of adherent endothelial precursor cells (EPCs) is a promising approach toward improving graft endothelialization. Designer Collagen Scl2-2 with 1 integrin binding site per strand (DC2-1X) is a Streptococcus pyogenes-derived, collagen-like protein that has previously been evaluated as a graft coating due to its ability to resist platelet aggregation and to promote attachment and migration of “late outgrowth” EPCs (EOCs). However, these prior assessments were performed in the absence of physiological shear. In addition, although DC2-1X coatings supported increased migration rates relative to native collagen coatings, EOC attachment and spreading remained inferior to collagen controls at all DC2-1X concentrations assayed. Thus, the objectives of the present work were the following: (1) to improve EOC attachment on DC2 coatings by modulating the number and spacing of DC2 integrin binding sites (IBS) and (2) to evaluate the retention, migration, and differentiation of adherent EOCs under physiological shear stress. Using single point mutations, three novel DC2 variants were generated containing either two IBS (DC2-2X) or three IBS (DC2-3X1 and DC2-3X2) per strand. After initial evaluation of the potential of each DC2 variant to support increased EOC attachment relative to DC2-1X, DC2-2X and DC2-3X1 coatings were further assessed under physiological shear for their capacity to promote EOC retention, migration, and differentiation relative to DC2-1X and collagen controls. An increase in the number of IBS from 1 to 3 significantly improved EOC retention on DC2 coatings while also supporting increased average migration rates. Moreover, EOCs on DC2-3X1 coatings showed increased gene-level expression of intermediate endothelial cell differentiation markers relative to collagen. Overall, the current results suggest that DC2-3X1 warrants further investigation as a vascular graft coating.