In the past two decades tissue adhesives and sealants have revolutionized hemostasis and wound management in traumatic and surgical injuries. Various biological-driven glues and synthetic adhesives are clinically utilized either as an adjunct to conventional hemostats and wound closure techniques, such as suturing, or as a replacement to them. The ability to effectively and promptly control bleeding, thus, reducing the risk of complications due to severe blood loss, in addition to convenience of use render medical adhesive a highly suitable tool for wound management. This review focuses on existing tissue adhesive systems, their structure, functioning mechanism, indicated and off-label applications, and limitations. 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 review 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.

The existing surgical adhesives are not ideal for wet tissue adhesion required in many surgeries such as those for internal organs. Developing surgical adhesives with strong wet tissue adhesion, controlled degradability and mechanical properties, and excellent biocompatibility has been a significant challenge. Herein, learning from nature, we report a one-step synthesis of a family of injectable citrate-based mussel-inspired bioadhesives (iCMBAs) for surgical use. Within the formulations investigated, iCMBAs showed 2.5–8.0 folds stronger wet tissue adhesion strength over the clinically used fibrin glue, demonstrated controlled degradability and tissue-like elastomeric mechanical properties, and exhibited excellent cyto/tissue-compatibility both in vitro and in vivo. iCMBAs were able to stop bleeding instantly and suturelessly, and close wounds (2 cm long × 0.5 cm deep) created on the back of Sprague-Dawley rats, which is impossible when using existing gold standard, fibrin glue, due to its weak wet tissue adhesion strength. Equally important, the new bioadhesives facilitate wound healing, and are completely degraded and absorbed without eliciting significant inflammatory response. Our results support that iCMBA technology is highly translational and could have broad impact on surgeries where surgical tissue adhesives, sealants, and hemostatic agents are used.

Injectable bone implants have been widely used in bone tissue repairs including the treatment of comminuted bone fractures (CBF). However, most injectable bone implants are not suitable for the treatment of CBF due to their weak tissue adhesion strengths and minimal osteoinduction. Citrate has been recently reported to promote bone formation through enhanced bioceramic integration and osteoinductivity. Herein, a novel injectable citrate-based mussel-inspired bioadhesive hydroxyapatite (iCMBA/HA) bone substitute was developed for CBF treatment. iCMBA/HA can be set within 2–4 minutes and the as-prepared (wet) iCMBA/HA possess low swelling ratios, compressive mechanical strengths of up to 3.2±0.27 MPa, complete degradation in 30 days, suitable biocompatibility, and osteoinductivity. This is also the first time to demonstrate that citrate supplementation in osteogenic medium and citrate released from iCMBA/HA degradation can promote the mineralization of osteoblastic committed human mesenchymal stem cells (hMSCs). In vivo evaluation of iCMBA/HA in a rabbit comminuted radial fracture model showed significantly increased bone formation with markedly enhanced three-point bending strength compared to the negative control. Neovascularization and bone ingrowth as well as highly organized bone formation were also observed showing the potential of iCMBA/HA in treating CBF.

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With the growing potential applications of nanoparticles in biomedicine especially the increasing concerns of nanotoxicity of gold nanoparticles, the interaction between protein and nanoparticles is proving to be of fundamental interest for bio-functionalization of materials. The interaction of glycine (Gly) amino acid with Au32 fullerene was first investigated with B3LYP-D3/TZVP model. Several forms of glycine were selected to better understand the trends in binding nature of glycine interacting with the nanocage. We have evaluated various stable configurations of the Gly/Au32 complexes and the calculated adsorption energies and AIM analysis indicate that non-Gly, z-Gly and also tripeptide glycine can form stable bindings with Au32 at aqueous solution via their amino nitrogen (N) and/or carbonyl/carboxyl oxygen (O) active sites. Furthermore, cysteine, tyrosine, histidine and phenylalanine amino acids bound also strongly to the Au32 nanocage. Electronic structures and quantum molecular descriptors calculations also demonstrate the significant changes in the electronic properties of the nanocage due to the attachment of selected amino acids. DFT based MD simulation for the most stable complex demonstrate that Gly/Au32 complex is quite stable at ambient condition. Our first-principles findings offer fundamental insights into the functionalization of Au32 nanocage and envisage its applicability as novel carrier of the drugs.

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Condensation of isonicotinic hydrazide and acetylacetone resulted in the formation of novel V-shape organic ligand (L) that consists of a six-membered pyridine and five-membered hydroxyl, dimethylsubstituted diazole cycles joined via carbonyl bridge [1]. The metathesis reaction between [Co(DfgH) 2 Br(H 2 O)] (DfgH 2 =diphenylglyoxime) and L resulted in mononuclear octahedral complex [Co(DfgH) 2 BrL] (1) with the substitution of water molecule in apical position by L ligand (Fig. 1). The dihedral angle between the cycle units is equal 49.5° in L in 1. The reaction starting from [Co(DmgH) 2 Cl(H 2 O)] (DmgH=dimethylglyoxime) and L resulted in the mononuclear octahedral Co(III) complex again with the composition [Co(DmgH) 2 ClL´] (2), were unexpectedly L´ represent the dehydrated derivative of L (Fig. 2). The dihedral angle between pyridine and diazole rings is equal 88.8° in L´ in 2. While the organic molecules L/L´ have several donor centers, both ligands act as monodentate ligands and coordinate with metal atom by nitrogen atom of pyridine fragment.