Sutures, wires, and staples constitute the conventional standard of care for reconnecting tissues after surgical procedures to restore their structure and function. These methods generally have several limitations. For example, they are time-consuming and may cause further tissue damage and lead to infection. In addition, they may not provide immediate and adequate sealing to stop body fluid and air leakages. Using adhesive biomaterials is a suitable alternative for wound closure due to their characteristics, such as simple and painless application, and short implementation time. In this regard, various types of surgical materials have been used for sealing, reconnecting tissues, or attaching devices to the tissues. Based on the final application and the anatomical parts involved in the medical intervention, it is important to design these tissue adhesives with some specific characteristics such as: i) high biocompatibility, ii) easy and rapid application, iii) strong adhesion to the target tissue, iv) biomimetic mechanical properties, v) permeability to nutrients and gases, vi) supporting tissue regeneration, and vii) antimicrobial properties in the case of infected wounds. However, commercially available surgical adhesives have many drawbacks and generally only possess one of the properties mentioned above. In this project, we aimed to combine different types of highly biocompatible biopolymers (e.g. gelatin, elastin like polypeptides, and hyaluronic acid) with different nanomaterials to engineer novel bioadhesives with the combined properties mentioned above. These biopolymers were first chemically modified to form photocrosslinakble hydrogels through a short exposure to visible light in the presence of a highly biocompatible photoinitiator (Eosin Y). The engineered adhesives exhibited tunable physical properties and could be tailored for a variety of surgical and tissue engineering applications. As the first step of the project, a flexible and transparent gelatin-based adhesive was designed for corneal tissue sealing and repair. The mechanical properties of the engineered hydrogel adhesive were optimized to mimic the stiffness of the native cornea. In addition, the formulation of the adhesive was modified to obtain high adhesion to the cornea, while retaining appropriate biodegradability and high cytocompatibility in vitro. Our data showed that the engineered hydrogel adhesives had higher adhesive strength than commercially available adhesives used for cornea such as ReSure� (Ocular Therapeutix, Inc., USA), based on standard adhesion tests by the American Society for Testing and Materials (ASTM). In addition, ex vivo tests on explanted rabbit eyes demonstrated that the adhesives possessed high retention and were resistant to burst pressure. Furthermore, in vivo tests were conducted using a rabbit stromal cornea defect model to test the biocompatibility and retention of the biomaterial, as well as corneal regeneration after the application. In the second part of this proposal, we modified our engineered hydrogels to fabricate multifunctional adhesives through incorporation of different drugs and nanomaterials. In particular, we engineered antimicrobial adhesives by incorporating ZnO nanoparticles (NPs) or antimicrobial peptides (Tet213) to the structure of the biopolymer prior to photopolymerization. In addition, we showed that the incorporation of laponite (disc shaped silicate NPs) could lead to the formation of osteoinductive adhesives that can be used for a wide range of applications, such as bone and dental tissue engineering. These multifunctional adhesive hydrogels exhibited high biocompatibility, mechanical stability and tissue integration in different animal models such as subcutaneous implantation in rats, and a mouse calvarial defect model. Our engineered multifunctional adhesives with tunable physical and adhesive properties can be used as a platform for sealing and repair of various tissues such as bone, lung, skin, and arteries.
