Hemostatic biomaterials show great promise in wound control for the treatment of uncontrolled bleeding associated with damaged tissues, traumatic wounds, and surgical incisions. A surge of interest has been directed at boosting hemostatic properties of bioactive materials via mechanisms triggering the coagulation cascade. A wide variety of biocompatible and biodegradable materials has been applied to the design of hemostatic platforms for rapid blood coagulation. Recent trends in the design of hemostatic agents emphasize chemical conjugation of charged moieties to biomacromolecules, physical incorporation of blood-coagulating agents in biomaterials systems, and superabsorbing materials in either dry (foams) or wet (hydrogel) states. In addition, tough bioadhesives are emerging for efficient and physical sealing of incisions. In this Review, we highlight the biomacromolecular design approaches adopted to develop hemostatic bioactive materials. We discuss the mechanistic pathways of hemostasis along with the current standard experimental procedures for characterization of the hemostasis efficacy. Finally, we discuss the potential for clinical translation of hemostatic technologies, future trends, and research opportunities for the development of next-generation surgical materials with hemostatic properties for wound management.

Controlling bleeding from a raptured tissue, especially during the surgeries, is essentially important. Particularly for soft and dynamic internal organs where use of sutures, staples, or wires is limited, treatments with hemostatic adhesives have proven to be beneficial. However, major drawbacks with clinically used hemostats include lack of adhesion to wet tissue and poor mechanics. In view of these, herein, we engineered a double-crosslinked sealant which showed excellent hemostasis (comparable to existing commercial hemostat) without compromising its wet tissue adhesion. Mechanistically, the engineered hydrogel controlled the bleeding through its wound-sealing capability and inherent chemical activity. This mussel-inspired hemostatic adhesive hydrogel, named gelatin methacryloyl-catechol (GelMAC), contained covalently functionalized catechol and methacrylate moieties and showed excellent biocompatibility both in vitro and in vivo . Hemostatic property of GelMAC hydrogel was initially demonstrated with an in vitro blood clotting assay, which showed significantly reduced clotting time compared to the clinically used hemostat, Surgicel®. This was further assessed with an in vivo liver bleeding test in rats where GelMAC hydrogel closed the incision rapidly and initiated blood coagulation even faster than Surgicel®. The engineered GelMAC hydrogel-based seaalant with excellent hemostatic property and tissue adhesion can be utilized for controlling bleeding and sealing of soft internal organs.

Injured tissues often require immediate closure to restore the normal functionality of the organ. In most cases, injuries are associated with trauma or various physical surgeries where different adhesive hydrogel materials are applied to close the wounds. However, these materials are typically toxic, have low elasticity, and lack strong adhesion especially to the wet tissues. In this study, a stretchable composite hydrogel consisting of gelatin methacrylol catechol (GelMAC) with ferric ions, and poly(ethylene glycol) diacrylate (PEGDA) was developed. The engineered material could adhere to the wet tissue surfaces through the chemical conjugation of catechol and methacrylate groups to the gelatin backbone. Moreover, the incorporation of PEGDA enhanced the elasticity of the bioadhesives. Our results showed that the physical properties and adhesion of the hydrogels could be tuned by changing the ratio of GelMAC/PEGDA. In addition, the in vitro toxicity tests confirmed the biocompatibility of the engineered bioadhesives.Finally, using an ex vivo lung incision model, we showed the potential application of the developed bioadhesives for sealing elastic tissues.

Cerebrovascular ischemia from intracranial atherosclerosis remains difficult to treat. Although current revascularization procedures, including intraluminal stents and extracranial to intracranial bypass, have shown some benefit, they suffer from peri-and postoperative morbidity. To address these limitations, here we developed a novel approach that involves gluing of arteries and subsequent transmural anastomosis from the healthy donor into the ischemic recipient. This approach required an elastic vascular sealant with distinct This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as

New vaccine platforms that properly activate humoral immunity and generate neutralizing antibodies are required to combat emerging and re-emerging pathogens, including influenza virus. Biomaterial scaffolds with macroscale porosity have demonstrated tremendous promise in regenerative medicine where they have been shown to allow immune cell infiltration and subsequent activation, but whether these types of materials can serve as an immunization platform is unknown. We developed an injectable immunization platform that uses a slurry of antigen-loaded hydrogel microparticles that anneal to form a porous scaffold with high surface area for antigen uptake by infiltrating immune cells as the biomaterial degrades to maximize humoral immunity. Antigen-loaded-microgels elicited a robust cellular humoral immune response, with increased CD4+ T follicular helper (Tfh) cells and prolonged germinal center (GC) B cells comparable to the commonly used adjuvant, aluminum hydroxide (Alum). By simply increasing the weight fraction of polymer material, we enhanced material stiffness and further increased antigen-specific antibody titers superior to Alum. Vaccinating mice with inactivated influenza virus loaded into this more highly crosslinked formulation elicited a strong antibody response and provided better protection against a high dose viral challenge than Alum. Thus, we demonstrate that by tuning physical and chemical properties alone, we can enhance adjuvanticity and promote humoral immunity and protection against a pathogen, leveraging two different types of antigenic material: individual protein antigen and inactivated virus. The flexibility of the platform may enable design of new vaccines to enhance innate and adaptive immune cell programming to generate and tune high affinity antibodies, a promising approach to generate long-lasting immunity against specific pathogens.