Insights on Chemical Crosslinking Strategies for Proteins

Abstract

Crosslinking of proteins has gained immense significance in the fabrication of biomaterials for various health care applications. Various novel chemical-based strategies are being continuously developed for intra-/inter-molecular crosslinking of proteins to create a network/matrix with desired mechanical/functional properties without imparting toxicity to the host system. Many materials that are used in biomedical and food packaging industries are prepared by chemical means of crosslinking the proteins, besides the physical or enzymatic means of crosslinking. Such chemical methods utilize the chemical compounds or crosslinkers available from natural sources or synthetically generated with the ability to form covalent/non-covalent bonds with proteins. Such linkages are possible with chemicals like carbodiimides/epoxides, while photo-induced novel chemical crosslinkers are also available. In this review, we have discussed different protein crosslinking strategies under chemical methods, along with the corresponding crosslinking reactions/conditions, material properties and significant applications.

Apigenin Self-Assembled Collagen Biomatrix for Reprogramming the Obese Wound Microenvironment for Its Management and Repair

“…Apigenin was found to cross-link collagen molecules by introducing hydrogen bonds between individual protein molecules. Active side chains of collagen proteins interacted with apigenin to form cross-linked polymeric proteins . The addition of cross-linkers initiates the formation of a lateral network of fibrils.…”

Protein‐Based Patterning to Spatially Functionalize Biomimetic Membranes

“…Conversely, to achieve immobile and ATP‐independent patterning of biomolecules after their diffusiophoretic positioning, crosslinking strategies can be applied. In this regard, physical and chemical crosslinking of proteins, [ 43 ] cation‐mediated fixing of DNA origami on membranes, [ 44 ] or the UV crosslinking of Min patterns would allow to utilize systems patterned by Min proteins on diverse buffer conditions and experimental set‐ups.…”

Influence of Natural Crosslinkers on Chitosan Hydrogels for Potential Biomedical Applications

“…In addition, there is a considerable risk involving the unreacted crosslinkers, which might remain inside the scaffolds, causing biocompatibility issues. [24,25] For this reason, the employment of natural crosslinkers is an increasing trend. The main advantages of natural crosslinkers are their low cost in most cases and their lack of cytotoxicity, although most crosslinkers are not as efficient as most synthetic crosslinkers.…”

“…The most frequently used natural crosslinkers are genipin, enzymes, citric and tannic acid, and some sugars such as glucose, sucrose, and fructose. [24,26,27] Genipin (G) is the most frequently used natural crosslinker, despite its high cost, for the development of crosslinked biomaterials, due to its outstanding biocompatibility, biodegradability, and stability of the resulting crosslinked products. [26,28] Hydrolysis with 𝛽-glucosidase of geniposide isolated from the fruits of Gardenia jasminoides Ellis produces the monoterpenoid genipin (methyl 1-hydroxy-7-(hydroxymethyl)−1,4a,5,7atetrahydrocyclopenta [c]pyran-4-carboxylate).…”

“…The most frequently used natural crosslinkers are genipin, enzymes, citric and tannic acid, and some sugars such as glucose, sucrose, and fructose. [ 24,26,27 ]…”