Design strategies and applications of tissue bioadhesives

Abstract

In the past two decades tissue adhesives and sealants have revolutionized bleeding control and wound healing. This paper focuses on existing tissue adhesive design, their structure, functioning mechanism, and their pros and cons in wound management. It also includes the latest advances in the development of new tissue adhesives as well as the emerging applications in regenerative medicine. We expect that this paper will provide insightful discussion on tissue bioadhesive design and lead to innovations for the development of the next generation of tissue bioadhesives and their related biomedical applications.

Figure 1

Schematic diagram of functioning mechanism of fibrin glue, resembling the last stage of physiological coagulation cascade in the body.

Figure 2

Schematic adhesion and crosslinking mechanisms of GRF/GRFG glue (gelatin resorcinol formaldehyde/glutaraldehyde).

Figure 3

Polymerization (A) and degradation (B) of cyanoacrylate adhesives.

Figure 4

Crosslinking and network formation of sealants based on dual-PEG (poly(ethylene glycol)) comprising two 4-arm PEGs capped with succinimidyl glutarate and thiol.

Figure 5

Tissue adhesion and crosslinking mechanisms of urethane-based adhesives.

Figure 6

Schematic diagram of plausible adhesion and crosslinking mechanisms of catechol-containing polymers, such as mussel adhesives.

Figure 7

Synthesis and plausible adhesion mechanisms of iCMBAs. (A) Schematic diagram of iCMBA synthesis using a condensation polymerization between citric acid, poly(ethylene glycol), and dopamine or L-DOPA. (B) Schematic representation of iCMBA adhesion to tissue and possible mechanisms.^[82]

Figure 8

Animal study of iCMBA in a rat model. Images of wounds created on rat’s dorsum and closed by iCMBA adhesive and suture at (A) 7th, and (B) 28th day post surgery. The sections of skin tissue of sacrificed rats at the site of wounds, which were treated by iCMBA and suture: (A) 7 days, and (B) 28 days post operation. (C) The opposite side of (B). iCMBA exhibited better hemostasis and wound treatment properties than suture. ^[82]

Figure 9

Bioadhesive in tissue engineering. Schematic illustration of adhesion between biomaterial hydrogel (dark blue) to cartilage tissue (light blue) by means of a functionalized chondroitin sulphate (CS), which covalently binds biomaterial to cartilage tissue surface. Using modified CS adhesive resulted in improved integration between CS, the biomaterial hydrogel, and the native tissue (Reprinted by permission from Macmillan Publishers Ltd: NATURE MATERIALS ^[87], copyright (2007)).