An Injectable Hybrid Gelatin Methacryloyl (GelMA)/Phenyl Isothiocyanate-Modified Gelatin (Gel-Phe) Bioadhesive for Oral/Dental Hemostasis Applications.

Wan-Chun Chang,Au-Zou Tai,Nian-Yun Tsai,Yi-Chen Ethan Li

doi:10.3390/polym13142386

Abstract

Biomaterials are widely used for effectively controlling bleeding in oral/dental surgical procedures. Here, gelatin methacryloyl (GelMA) was synthesized by grafting methacrylic anhydride on gelatin backbone, and phenyl isothiocyanate-modified gelatin (Gel-Phe) was synthesized by conjugating different gelatin/phenyl isothiocyanate molar ratios (G/P ratios) (i.e., 1:1, 1:5, 1:10, 1:15, 1:25, 1:50, 1:100, and 1:150) with gelatin polymer chains. Afterward, we combined GelMA and Gel-Phe as an injectable and photo-crosslinkable bioadhesive. This hybrid material system combines photo-crosslinking chemistry and supramolecular interactions for the design of bioadhesives exhibiting a highly porous structure, injectability, and regulable mechanical properties. By simply regulating the G/P ratio (1:1–1:15) and UV exposure times (15–60 s), it was possible to modulate the injectability and mechanical properties of the GelMA/Gel-Phe bioadhesive. Moreover, we demonstrated that the GelMA/Gel-Phe bioadhesive showed low cytotoxicity, a highly porous network, and the phenyl-isothiourea and amine residues on Gel-Phe and GelMA polymers with synergized hemostatic properties towards fast blood absorption and rapid clotting effect. An in vitro porcine skin bleeding and an in vitro dental bleeding model confirmed that the bioadhesive could be directly extruded into the bleeding site, rapidly photo-crosslinked, and reduced blood clotting time by 45%. Moreover, the in situ crosslinked bioadhesive could be easily removed from the bleeding site after clotting, avoiding secondary wound injury. Overall, this injectable GelMA/Gel-Phe bioadhesive stands as a promising hemostatic material in oral/dental surgical procedures.

Highlights

Excessive hemorrhage complicates surgical processes and increases the mortality rate
Bioadhesives have assumed a major role in developing hemostatic agents because of their operable property and rapid in situ gelation behavior, as well as the ability to attach onto irregular wounds, offering an effective alternative to traditional sponges and gauze-type hemostatic substrates in oral/dental surgical procedures [36]
This study developed a hybrid injectable bioadhesive with tunable mechanical properties and supramolecular interactions based on gelatin methacryloyl (GelMA) and Gel-phenyl isothiocyanate (Phe) (Figure 1)

Summary

Introduction

Excessive hemorrhage complicates surgical processes and increases the mortality rate. Shaikh et al reported that controlling continuous blood oozing, the space for blood clots, and blood clot stabilization are highly relative to dental wound healing after surgical procedure [3]. They mentioned that a thick blood clot might induce poor plasmatic circulation and affect the healing between graft and gingival tissues at the initial healing stage [3]. Bone wax is a paraffin-based material used for bone bleeding during tooth extraction, but the non-resorbable property of bone wax may affect osteogenesis [7] These non-resorbable sealants may produce undesired side effects on soft tissues in oral surgery

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Results

Conclusion