Wound healing is a complex tissue regeneration process that promotes the growth of new tissue to provide the body with the necessary barrier from the outside environment. In the class of non-healing wounds, diabetic wounds, and ulcers, dressing materials that are available clinically (e.g., gels and creams) have demonstrated only a slow improvement with current available technologies. Among all available current technologies, electrospun fibers exhibit several characteristics that may provide novel replacement dressing materials for the above-mentioned wounds. Therefore, in this review, we focus on recent achievements in electrospun drug-eluting fibers for wound healing applications. In particular, we review drug release, including small molecule drugs, proteins and peptides, and gene vectors from electrospun fibers with respect to wound healing. Furthermore, we provide an overview on multifunctional dressing materials based on electrospun fibers, including those that are capable of achieving wound debridement and wound healing simultaneously as well as multi-drugs loading/types suitable for various stages of the healing process. Our review provides important and sufficient information to inform the field in development of fiber-based dressing materials for clinical treatment of non-healing wounds.

Hemocompatibility remains a challenge for injectable and/or implantable medical devices, and thromboresistant coatings appear to be one of the most attractive methods to down-regulate the unwanted enzymatic reactions that promote the formation of blood clots. Among all polymeric materials, polyurethanes (PUs) are a class of biomaterials with excellent biocompatibility and bioinertness that are suitable for the use of thromboresistant coatings. In this work, we investigated the thermal and physico-mechanical behaviors of ester-based and ether-based PU films for potential uses in thromboresistant coatings. Our results show that poly(ester urethane) and poly(ether urethane) films exhibited characteristic peaks corresponding to their molecular configurations. Thermal characterizations suggest a two-step decomposition process for the poly(ether urethane) films. Physico-mechanical characterizations show that the surfaces of the PU films were hydrophobic with minimal weight changes in physiological conditions over 14 days. All PU films exhibited high tensile strength and large elongation to failure, attributed to their semi-crystalline structure. Finally, the in vitro clotting assays confirmed their thromboresistance with approximately 1000-fold increase in contact time with human blood plasma as compared to the glass control. Our work correlates the structure-property relationships of PU films with their excellent thromboresistant ability.

Advances in nanotechnology and nanomaterials have enabled the development of functional biomaterials with surface properties that reduce the rate of the device rejection in injectable and implantable biomaterials. In addition, the surface of biomaterials can be functionalized with macromolecules for stimuli-responsive purposes to improve the efficacy and effectiveness in drug release applications. Furthermore, macromolecule-grafted surfaces exhibit a hierarchical nanostructure that mimics nanotextured surfaces for the promotion of cellular responses in tissue engineering. Owing to these unique properties, this review focuses on the grafting of macromolecules on the surfaces of various biomaterials (e.g., films, fibers, hydrogels, and etc.) to create nanostructure-enabled and macromolecule-grafted surfaces for biomedical applications, such as thrombosis prevention and wound healing. The macromolecule-modified surfaces can be treated as a functional device that either passively inhibits adverse effects from injectable and implantable devices or actively delivers biological agents that are locally based on proper stimulation. In this review, several methods are discussed to enable the surface of biomaterials to be used for further grafting of macromolecules. In addition, we review surface-modified films (coatings) and fibers with respect to several biomedical applications. Our review provides a scientific update on the current achievements and future trends of nanostructure-enabled and macromolecule-grafted surfaces in biomedical applications.

Reactivity of factor IXa with basic pancreatic trypsin inhibitor is enhanced by low molecular weight heparin (enoxaparin). Previous studies by us have suggested that this effect involves allosteric modulation of factor IXa. We examined the reactivity of factor IXa with several isolated Kunitz-type inhibitor domains: basic pancreatic trypsin inhibitor, the Kunitz inhibitor domain of protease Nexin-2, and the first two inhibitor domains of tissue factor pathway inhibitor. We find that enhancement of factor IXa reactivity by enoxaparin is greatest for basic pancreatic trypsin inhibitor (>10-fold), followed by the second tissue factor pathway inhibitor domain (1.7-fold) and the Kunitz inhibitor domain of protease Nexin-2 (1.4-fold). Modeling studies of factor IXa with basic pancreatic trypsin inhibitor suggest that binding of this inhibitor is sterically hindered by the 99-loop of factor IXa, specifically residue Lys⁹⁸. Slow-binding kinetic studies support the formation of a weak initial enzyme-inhibitor complex between factor IXa and basic pancreatic trypsin inhibitor that is facilitated by enoxaparin binding. Mutation of Lys⁹⁸ to Ala in factor IXa results in enhanced reactivity with all inhibitors examined, whereas almost completely abrogating the enhancing effects of enoxaparin. The results implicate Lys⁹⁸ and the 99-loop of factor IXa in defining enzyme inhibitor specificity. More importantly, these results demonstrate the ability of factor IXa to be allosterically modulated by occupation of the heparin-binding exosite.