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Surgical adhesives are an attractive alternative to traditional mechanical tissue fixation methods of sutures and staples. Ease of application, biocompatibility, enhanced functionality (drug delivery) are known advantages but weak adhesion strength in the wet environment and lack of tissue compliant behavior still pose a challenge. In order to address these issues, non-aqueous bioadhesive based on blends of polyamidoamine (PAMAM) dendrimer, conjugated with 4-[3-(trifluoromethyl)-3H-diazirin-3-yl] benzyl bromide (PAMAM-g-diazirine) and liquid polyethylene glycol (PEG 400) has been developed. PEG 400 biocompatible solvent reduces the viscosity of PAMAM-g-diazirine dendrimer without incorporating aqueous solvents or plasticizers, allowing application by syringe or spray. Upon UV activation, diazirine-generated reactive intermediates lead to intermolecular dendrimer crosslinking. The properties of the crosslinked matrix are tissue compliant, with anisotropic material properties dependent on the PEG 400 wt%, UV dose, pressure and uncured adhesive thickness. The hygroscopic PAMAM-g-diazirine/PEG 400 blend was hypothesized to absorb water at the tissue interface, leading to high interfacial adhesion, however porous matrices led to cohesive failure. The hydrophilic nature of the polyether backbone (PEG 400) shielded cationic PAMAM dendrimers with cured bioadhesive film displaying significantly less platelet activation than neat PAMAM-g-diazirine or PLGA thin films., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Bioadhesives are a current unmet clinical need for mending of blood contacting soft tissues without inducing thrombosis. Recent development of carbene precursor bioadhesives with the advantages of on-demand curing, tuneable modulus, and wet adhesion have been synthesized by grafting diazirine onto poly (amidoamine) (PAMAM-G5) dendrimers. Herein, the structure activity relationships of platelet adhesion and activation is evaluated for the first time on the cured PAMAM-g-diazirine bioadhesives. Three strategies were employed to prevent healthy human donor platelets from adhering and activating on light-cured bioadhesive surfaces: (1) Attenuation of cationic surface charge, (2) antifouling composites by incorporating heparin and alginate in uncured formulation, and (3) heparin wash of cured bioadhesive surface. Topographical imaging of cured and ethanol dehydrated bioadhesive surfaces was used to quantify the adhered and activated platelets with scanning electron microscopy, whose resolution allowed identification of round senescent, short dendritic, and long dendritic platelets. Cured surfaces of PAMAM-g-diazirine (15%) had 10300 ± 500 adhered platelets mm -2 with 99.7% activation into short/long dendritic cells. Reduction of primary amines by higher degree of diazirine grafting or capping of free amines by acetylation reduces platelet adherence (2400 ± 200 vs 3000 ± 300, respectively). Physical incorporation of heparin and alginate in the formulations reduced the activated platelet; 1300 ± 300 and 300 ± 50, activated platelets mm -2 , in comparison with additive free adhesive formulation. Similarly, heparin rinse of the surface of additive free bioadhesive reduced the activated platelet to platelets of heparin composites at 600 ± 100 platelets mm -2 . PAMAM-g-diazirine (15%) bioadhesive retained the photocured mechanical properties and lap shear adhesion despite the addition of heparin and alginate additives.