Transglutaminase as a Tissue Glue (Pradeep Panengad)

The clinical caseload of surgical wounds is very high and physicians have long sought an efficient biological tissue glue which will replace surgical sutures and minimizes the discomfort for their patients, yet produces a good cosmetic outcome. Transglutaminases (TGases) constitute a family of 7 isoenzymes that stabilize protein assemblies by γ-glutamyl-ε-lysine crosslinks.

Fig1. Schematic diagram of transglutaminase-reaction cross linking peptide chains

Our aim is to develop biological tissue glue based on extra cellular matrix stabilizing enzyme transglutaminase 2 to covalently bond tissue layers to promote suture-less closure of surgical wounds (Fig. 2).

Fig 2. The idea of applying transglutaminase as biological glue

Transglutaminase as biological tissue adhesive

Enzyme Transglutaminase is naturally expressed in skin, helping supra-molecular assembly of ECM proteins in dermis as well as epithelial proteins in superficial layers of epidermis (Fig 3). Applying a native enzyme as tissue glue could be more biocompatible than currently used polymer based tissue adhesives.

Fig.3. Assay of TGase activity on human skin. (A) Endogenous TGase activity in skin incorporates tagged substrate peptides in the presence of calcium at pH 8.4. Preferential activity is seen as zone of green fluorescence in both dermis (TGase2) (white triangle) and epidermis (TGase1) (white arrow). (A’): Calcium chelation with EGTA abolished enzymatic activity.