Engineering a highly elastic human protein–based sealant for surgical applications

Abstract

Surgical sealants have been used for sealing or reconnecting ruptured tissues but often have low adhesion, inappropriate mechanical strength, cytotoxicity concerns, and poor performance in biological environments. To address these challenges, we engineered a biocompatible and highly elastic hydrogel sealant with tunable adhesion properties by photocrosslinking the recombinant human protein tropoelastin. The subcutaneous implantation of the methacryloyl-substituted tropoelastin (MeTro) sealant in rodents demonstrated low toxicity and controlled degradation. All animals survived surgical procedures with adequate blood circulation by using MeTro in an incisional model of artery sealing in rats, and animals showed normal breathing and lung function in a model of surgically induced rat lung leakage. In vivo experiments in a porcine model demonstrated complete sealing of severely leaking lung tissue in the absence of sutures or staples, with no clinical or sonographic signs of pneumothorax during 14 days of follow-up. The engineered MeTro sealant has high potential for clinical applications because of superior adhesion and mechanical properties compared to commercially available sealants, as well as opportunity for further optimization of the degradation rate to fit desired surgical applications on different tissues.

Synthesis and characterization of osteoinductive visible light‐activated adhesive composites with antimicrobial properties

“…Hydrogels were synthesized using varying concentrations of BG‐5/5 (1, 5, 10, and 20% [w/v]) as described above. The shear strength of the composites was evaluated according to a modified ASTM F2255‐05 standard test (Annabi, Zhang, et al, ). Briefly, composites were formed in situ by pipetting 10 μl of the precursors between two pieces of gelatin‐coated glass slides followed by photocrosslinking via visible light.…”

Engineering a naturally-derived adhesive and conductive cardiopatch

“…We also evaluated the ability of GelMA/Bio-IL cardiopatches to seal tissue defects under applied pressure using collagen sheets based on a standard burst pressure test [37,38] ( Figure S7c-d), as well as ex vivo explanted rat hearts ( Fig. 2d-e).…”

“…While different alternatives such as medical grade cyanoacrylates [32] and other bioadhesives [33][34][35] have been developed to adhere these patches on the heart, many of these approaches are associated with cytotoxicity and high stiffness (e.g cyanoacrylates), low adhesion and structural stability (e.g. fibrin-based bioadhesives), as well as failure to provide a biomimetic environment that allows for tissue regeneration [12,[36][37][38]. Therefore, there is an unmet need for engineering highly biocompatible and electroconductive fibrous scaffolds, which can adhere strongly to the myocardium to facilitate biointegration without the need for suturing.…”

Non-cytotoxic Dityrosine Photocrosslinked Polymeric Materials With Targeted Elastic Moduli

“…Despite the benefits of Ru-mediated dityrosine photocrosslinking, there is disagreement about the possible cytotoxicity of the Ru and persulfate crosslinking reagents (Annabi et al, 2017). In preparation of dityrosine photocrosslinked polymeric materials, persulfate concentrations have ranged from at least 1 to 200 mM, and Ru concentrations from 0.1 to 3 mM (Elvin et al, 2005(Elvin et al, , 2010Fang and Li, 2012;Ding et al, 2013;Jeon et al, 2015;Kim et al, 2017;Zhang et al, 2017;Min et al, 2018;Sakai et al, 2018;Khanmohammadi et al, 2019;Lim et al, 2019).…”