Elastic sealants for surgical applications

Abstract

Sealants have emerged as promising candidates for replacing sutures and staples to prevent air and liquid leakages during and after the surgeries. Their physical properties and adhesion strength to seal the wound area without limiting the tissue movement and function are key factors in their successful implementation in clinical practice. In this contribution, the advances in the development of elastic sealants formed from synthetic and natural materials are critically reviewed and their shortcomings are pointed out. In addition, we highlight the applications in which elasticity of the sealant is critical and outline the limitations of the currently available sealants. This review will provide insights for the development of novel bioadhesives with advanced functionality for surgical applications.

Keywords: Adhesion; Elasticity; Hydrogel; Surgical applications; Surgical sealants; Tissue adhesives.

Figure 1

Elastic PVA-based bioadhesives. (a) Synthesis of PVA-Ph. (b) Wound was treated by applying the pre-hydrogel solution. (c) Formation of PVA-based hydrogel was achieved via the reactions catalyzed by GOx and HRP with the presence of glucose in the exudate. (d) PVA-based adhesive formed onto a cellulose dialysis membrane. Adapted from Ref [23] with permission from The Royal Society of Chemistry, copyright 2013.

Figure 2

Typical reactions used for crosslinking in polypeptide/protein-based sealants. (A) Ru-catalyzed visible light promoted reaction to chemically crosslink tyrosine-containing proteins and polypeptides via the formation of dityrosine linkages [30]. (B) Crosslinking mechanism of GRF or GRFG sealants, including (i) the reaction between lysine residues and formaldehyde, (ii) Schiff base formation between lysine residues and glutaraldehyde, and (iii) formation of the network structure from formaldehyde and resorcinol [–41]. (C) Reaction between NHS-activated poly(L-glutamic acid) and gelatin [42]. (D) Reaction between the glutamine residue and lysine residue catalyzed by mTG [46].

Figure 3

Representative chemical structures of polysaccharide-based sealants. (A) Deacetylation of chitin generates chitosan with different degrees of acetylation, and various chemically modified chitosan derivatives are obtained by reacting chitosan with (i) lactobionic acid, (ii) 4-azidobenzoic acid, (iii) succinic anhydride, ((iv) PEG oligomers, (v) N-acetylcysteine, and (vi) 3-mercaptopropionic acid at the amine site [–57]. (B) Preparation of aldehyde-containing dextran via selective partial oxidation by periodide [60, 61]. (C) Chemical modification of chondroitin sulfate to introduce (i) methacrylate groups via reacting with glycidyl methacrylate [63], (ii) aldehyde groups via the oxidation reaction by periodide [64], and (iii) NHS-activated ester groups [66].

Figure 4

(A) Schematic diagram showing application of the chondroitin sulfate-based adhesive for hydrogel-tissue integration. The yellow colored layer indicated the chondroitin sulfate layer which served as the bridge between the cartilage tissue and the hydrogel. (B) In vivo subcutaneous implantation of the integrated cartilage-hydrogel constructs in a mice model. (C) Sample explantation after 5 weeks. (D) Safranin-O was found throughout the hydrogel layer and at the interface between the engineered and native cartilage tissues. Adapted from Ref [66] with permission from Nature Publishing Group, copyright 2007.

Figure 5

Highly elastic PGS-based glue for cardiovascular surgeries. (a) Explanted rat heart treated by the engineered glue after 14 days and corresponding H&E staining of the tissue in contact with the glue. (b) H&E and MT staining of the rat cardiac tissue after 1 and 6 months of defect closure with the glue, showing the formation of scarring and accumulation of organized collagen (scale bars: 1mm). (c) H&E staining of Pig carotid artery after treating with glue (scale bars: 1 mm (left) and 50 µm (right). The arrow points to the defect created. (d) Pig carotid artery one hour after incision creation and 24 hours after closure with HLAA. No bleeding was detected at the defects after 24 h of operation, as indicated by arrows. Adapted from Ref [5] with permission from the AAAS, copyright 2014.

Figure 6

Surgical sealants as skin wound closures. (a) Photographs of a dendritic thioester hydrogel adhered to human skin under torsion. (b-c) an injectable iCMBA adhesive for sutureless wound closure; (b) schematic of iCMBA adhesive for wound closure, (c) images from dorsum skin treated by the adhesive and suture 7 days post operation, which shows that the wounds were closed by both methods (red arrows), and (d) H&E images of wounds closed by iCMBA adhesives and suture at day 7 post treatment. Panels a, c, and d are adapted from Ref [112] with permission from Elsevier, copyright 2012; panel b is adapted from Ref [113] with permission from Wiley, copyright 2013.