Development of Multilayer Vascular Grafts Based on Collagen-Mimetic Hydrogels

Current synthetic vascular grafts have high failure rates in small-diameter (<6 mm) applications due to inadequate cell-material interactions and poor matching of arterial biomechanical properties. To address this, we have developed a multilayer vascular graft design with a non-thrombogenic inner layer that promotes endothelial cell (EC) interactions and a reinforcing layer with tunable biomechanical properties. The blood-contacting layer of the graft is based on a Streptococcal collagen-like protein (Scl2-1). Scl2-1 has the triple helical structure of collagen, but it is a non-thrombogenic protein that can be modified to have selective cell adhesion. For this application, Scl2-2 has been modified from Scl2-1 to contain integrin binding sites that promote EC adhesion. We have developed the methodology to incorporate Scl2 proteins into a poly(ethylene glycol) (PEG) hydrogel matrix. PEG-Scl2 hydrogels facilitate optimization of both bioactivity and substrate modulus to offer unique control over graft endothelialization. However, scaffold properties that promote endothelialization may not be consistent with the mechanical properties necessary to withstand physiological loading. To address this issue, we have reinforced PEG-Scl2-2 hydrogels with an electrospun polyurethane mesh. This multilayer vascular graft design decouples requisite mechanical properties from endothelialization processes and permits optimization of both design goals. We have confirmed the thromboresistance of PEG-Scl2-2 hydrogels in a series of whole blood tests in vitro as well as in a porcine carotid artery model. Additionally, we have shown that the electrospun mesh biomechanical properties can be tuned over a wide range to achieve comparable properties to current autologous grafts. Traditional acrylate-derivatized PEG (PEGDA) hydrogels were replaced with PEG diacrylamide hydrogels with similar properties to increase biostability for long-term implantation. These findings indicate that this multilayer design shows promise for vascular graft applications. As vascular graft endothelialization can significantly improve success rates, the ability to alter cell-material interactions through manipulations in PEG-Scl2-2 hydrogel properties was studied extensively. By reducing Scl2-2 functionalization density and utilizing a biostable PEG functionalization linker, Acrylamide-PEG-I, significantly improved initial EC adhesion was achieved that was maintained over 6 weeks of swelling in vitro. Additionally, increases in Scl2-2 concentration and in hydrogel modulus provided increased EC interactions. It was found that PEG-Scl2-2 hydrogels promoted enhanced EC proliferation over 1 week compared to PEG-collagen gels. In summary, we have developed a vascular graft with a biostable, non-thrombogenic intimal layer that promotes EC adhesion and migration while providing biomechanical properties comparable to current autologous grafts. This design demonstrates great potential as an off-the-shelf graft for small diameter arterial prostheses that improves upon current clinically available options

Mini-review antimicrobial smart materials: the future’s defense against wound infections

The overuse of antibiotics to treat bacterial infections along with bacteria’s propensity to form biofilm communities has resulted in an alarming rise in drug-resistant microbes. Current approaches to infection surveillance and biofilm clearance in wounds are severely limited, requiring new biomaterials-based strategies to address this problem. To that end, a range of antimicrobial smart materials have been developed that change their properties in response to bacteria-induced external stimuli, providing tools with an additional level of complexity for defending against microbes. Researchers have tried to tackle this issue using materials that respond to the unique pH, temperature, and enzymatic changes that are induced by bacteria in wounds. These environmental responses are coupled with mechanisms to kill surrounding bacteria and/or to signal infection. For example, bacteria-responsive biomaterial solubilization (transition from non-solubilized solid material to solubilized liquid solution), swelling (volumetric increase due to absorption of surrounding media), de-swelling, degradation, or shape change can be coupled with drug release and/or activation or biofilm disruption, inhibition, or destruction. These materials provide a foundation for future work and improvements related to enhanced infection surveillance, increased specificity of infection response, and effective clearance of biofilms from wound surfaces

On liberalism and its theology in Anglo-America: A linguistic and historical exploration.

On liberalism and its theology in Anglo-America: A linguistic and historical exploration

Shape Memory Polymer Foams with Phenolic Acid-Based Antioxidant Properties

Phenolic acids (PAs) are natural antioxidant agents in the plant kingdom that are part of the human diet. The introduction of naturally occurring PAs into the network of synthetic shape memory polymer (SMP) polyurethane (PU) foams during foam fabrication can impart antioxidant properties to the resulting scaffolds. In previous work, PA-containing SMP foams were synthesized to provide materials that retained the desirable shape memory properties of SMP PU foams with additional antimicrobial properties that were derived from PAs. Here, we explore the impact of PA incorporation on SMP foam antioxidant properties. We investigated the antioxidant effects of PA-containing SMP foams in terms of in vitro oxidative degradation resistance and cellular antioxidant activity. The PA foams showed surprising variability; p-coumaric acid (PCA)-based SMP foams exhibited the most potent antioxidant properties in terms of slowing oxidative degradation in H2O2. However, PCA foams did not effectively reduce reactive oxygen species (ROS) in short-term cellular assays. Vanillic acid (VA)- and ferulic acid (FA)-based SMP foams slowed oxidative degradation in H2O2 to lesser extents than the PCA foams, but they demonstrated higher capabilities for scavenging ROS to alter cellular activity. All PA foams exhibited a continuous release of PAs over two weeks. Based on these results, we hypothesize that PAs must be released from SMP foams to provide adequate antioxidant properties; slower release may enable higher resistance to long-term oxidative degradation, and faster release may result in higher cellular antioxidant effects. Overall, PCA, VA, and FA foams provide a new tool for tuning oxidative degradation rates and extending potential foam lifetime in the wound. VA and FA foams induced cellular antioxidant activity that could help promote wound healing by scavenging ROS and protecting cells. This work could contribute a wound dressing material that safely releases antimicrobial and antioxidant PAs into the wound at a continuous rate to ideally improve healing outcomes. Furthermore, this methodology could be applied to other oxidatively degradable biomaterial systems to enhance control over degradation rates and to provide multifunctional scaffolds for healing

Shape Memory Polymer Foams Synthesized Using Glycerol and Hexanetriol for Enhanced Degradation Resistance

Shape memory polymer foams have been used in a wide range of medical applications, including, but not limited to, vessel occlusion and aneurysm treatment. This unique polymer system has been proven to shape-fill a void, which makes it useful for occlusion applications. While the shape memory polymer foam has superior performance and healing outcomes compared to its leading competitors, some device applications may benefit from longer material degradation times, or degradation-resistant formulations with increased fibrous encapsulation. In this study, biostable shape memory polymer foams were synthesized, and their physical and chemical properties were characterized as an initial evaluation of feasibility for vascular occlusion applications. After characterizing their shape memory behavior in an aqueous environment, degradation of this polymer system was studied in vitro using accelerated oxidative and hydrolytic solutions. Results indicated that the foams did not lose mass under oxidative or hydrolytic conditions, and they maintained high shape recovery in aqueous in vitro models. These degradation-resistant systems have potential for use in vascular occlusion and other wound healing applications that benefit from permanent, space-filling shape memory behavior

Designer collagens and use thereof

The present disclosure provides synthetic collagen and methods of making and using synthetic collagen that include a synthetic collagen that facilitates wound closure comprising an isolated and purified triple helical backbone protein that facilitates wound closure comprising one or more alteration in a triple helical backbone protein sequence, that stabilize the isolated and purified triple helical backbone protein and does not disrupt an additional collagen ligand interaction; and one or more integrin binding motifs, wherein the isolated and purified triple helical backbone protein facilitates wound closure.U

Designer collagens and use thereof

The present disclosure provides synthetic collagen and methods of making and using synthetic collagen that include a synthetic collagen that facilitates wound closure comprising an isolated and purified triple helical backbone protein that facilitates wound closure comprising one or more alteration in a triple helical backbone protein sequence, that stabilize the isolated and purified triple helical backbone protein and does not disrupt an additional collagen ligand interaction; and one or more integrin binding motifs, wherein the isolated and purified triple helical backbone protein facilitates wound closure.U