A Novel Multifunctional Injectable Polyxylitol Succinate-Based Bioadhesive for Periodontal Regeneration

Abstract

<p><strong>Objectives</strong>: To formulate a novel injectable adhesive hydrogel with antibacterial and osteogenic properties to promote periodontal regeneration.<br><strong>Methods</strong>: A novel polyxylitol succinate(PXS) polymer was prepared by esterifying xylitol with succinyl chloride. Adhesive properties were subsequently incorporated into the prepolymer by combining biocompatible catechol via caffeic acid (CFA). The PXS and CFA were subjected to citric acid in a one-pot synthesis. The final injectable caffeic acid/PXS/citric acid composite polymer(iCPC) hydrogel was fabricated by cross-linking the pre-polymer solution with MgO. PXS and iCPC polymers were characterized by proton nuclear magnetic resonance (¹H NMR) spectra; adhesiveness, biocompatibility, and biodegradation were optimized; intrinsic anti-bacterial effects and osteogenic properties were studied. The rat periodontitis model was used to assess the iCPC <em>in vivo</em>. Micro-CT (radiographic bone loss) and immunohistochemistry (IL-1b, IL-6, TNF-a) were utilized to examine the healing and regeneration of periodontal tissue. Statistical analysis was performed using one-way ANOVA and Tukey multiple comparison tests.<br><strong>Results</strong>: In iCPC polymer, specific peaks (¹H NMR) in the chemical shifts, which can be ascribed to CFA, confirmed the successful conjugation of CFA to the polymer backbone. Lap shear adhesion test results showed superior adhesive properties of iCPC compared to fibrin glue(P<0.05). Optimal swelling ratios and degradation rates observed in iCPC over 48 hours. CCK-8 and live/dead staining results indicated that iCPC hydrogels could enhance the proliferation of human periodontal ligament cells. The intrinsic antimicrobial effect of iCPC was demonstrated by inhibiting the growth of <em>A.actinomycetemcomitans</em> and <em>P.gingivalis</em> responsible for periodontitis (P<0.05). hPDLCs demonstrate superior osteogenic properties when grown in iCPC hydrogel (P<0.05) and showed enhanced Runx2 expression via western blotting (P<0.05). Micro-CT and IHC staining showed that iCPC could reduce radiographic bone loss (P<0.05) and promote periodontal tissue regeneration in rats.<br><strong>Conclusions</strong>: iCPC hydrogel possesses excellent tissue-adhesive, antibacterial, and osteogenic properties and stimulates periodontal regeneration in vivo.<br></p>