Photoinduced Porcine Gelatin Cross-Linking by Homobi- and Homotrifunctional Tetrazoles

Abstract

Gelatin is a costless polypeptide material of natural origin, able to form hydrogels that are potentially useful in biomaterial scaffold design for drug delivery, cell cultures, and tissue engineering. However, gelatin hydrogels are unstable at physiological conditions, losing their features only after a few minutes at 37 °C. Accordingly, treatments to address this issue are of great interest. In the present work, we propose for the first time the use of bi- and trifunctional tetrazoles, most of them unknown to date, for photoinduced gelatin cross-linking towards the production of physiologically stable hydrogels. Indeed, after UV-B irradiation, aryl tetrazoles generate a nitrilimine intermediate that is reactive towards different functionalities, some of them constitutively present in the amino acid side chains of gelatin. The efficacy of the treatment strictly depends on the structure of the cross-linking agent used, and substantial improved stability was observed by switching from bifunctional to trifunctional cross-linkers.

Biomaterials for Regenerative Medicine in Italy: Brief State of the Art of the Principal Research Centers

“…The Department of Biotechnology and Biosciences (Milan University) and the Milan-Bicocca University have functionalized the gelatin polymer to improve mechanical stability at physiological temperatures. Cross-linked gelatin has been generated by homobifunctional triazolinediones [ 43 ], and homobi- and homotri-functional tetrazoles in order to obtain more stable hydrogels [ 44 ]. Instead, the Polytechnic of Milan studied pectin hydrogel for tissue engineering applications.…”

“… Materials Characteristics Applications Ref. Alginate Micro-structured hydrogel Bioprintable Accelerate wound closure Drug delivery Cancer model (neuroblastoma) Wound healing [ 1 , 2 , 9 , 12 ] Chitosan Chitin derivative Bioprintable Soft tissue engineering Mechano-responsive biomaterial Wound healing [ 3 , 4 , 13 , 14 , 21 , 22 , 23 ] dECM hydrogels Contains growth and differentiative factors Myogenic potential Organoid culture Skeletal muscle tissue engineering [ 37 , 38 , 39 , 40 ] Gelatin Collagen derivative Mechanically stable Drug delivery Cell culture Tissue engineering [ 43 , 44 ] Hyaluronic acid Component of connective tissue Injectable Cell culture Treatment of meniscal lesions Intervertebral disc regeneration Wound healing [ …”

Engineering biomolecular systems: Controlling the self-assembly of gelatin to form ultra-small bioactive nanomaterials

“…Researchers have altered pH, temperature, and crosslinker to synthesize smaller GNPs. But these attempts thus far have generated GNPs larger than 100 nm, and particles smaller than that have not been obtained [ [25] , [26] , [27] ]. In an interesting study, researchers tried to shrink GNPs to 100 nm using a freeze-thaw method [ 28 ].…”

Thermally Activable Bistetrazoles for Elastomers Crosslinking

“…Addition of molecular species able to covalently cross-link the elastomers at the right stage of the process could be the solution of the aforementioned problems. We were attracted by tetrazole moiety, that can be thermally activated to form a nitrilimine intermediate displaying high reactivity toward several functional groups ( Scheme 1 ) [ 14 , 15 , 16 , 17 , 18 ], including 3+2 cycloaddition to pyrazoline in presence of C-C double bonds, which are abundant in polymers used for tires. Moreover, with the same type of substituents, the less the double bond is substituted, the better the reactivity of the cycloaddition [ 19 , 20 , 21 , 22 ], assuming a selectivity toward the vinyl bonds of elastomers.…”