Injectable mineralized Sr-hydroxyapatite nanoparticles-loaded ɛ-polylysine-hyaluronic acid composite hydrogels for bone regeneration
A. Yu. Rubina, Artemijs Ščeglovs, Anna Ramata‐Stunda, I Pugajeva, Ingus Skadiņš, Adrian Boyd, Anastasija Tumilovica, Līga Stīpniece, Kristīne Šalma-Ancāne
Abstract
In this study, multifunctional injectable mineralized antibacterial nanocomposite hydrogels were prepared by a homogenous distribution of high content of (up to 60 wt%) Sr-substituted hydroxyapatite (Sr-HAp) nanoparticles into covalently cross-linked ɛ-polylysine (ɛ-PL) and hyaluronic acid (HA) hydrogel network. The developed bone-targeted nanocomposite hydrogels were to synergistically combine the functional properties of bioactive Sr-HAp nanoparticles and antibacterial ɛ-PL-HA hydrogels for bone tissue regeneration. Viscoelasticity, injectability, structural parameters, degradation, antibacterial activity, and in vitro biocompatibility of the fabricated nanocomposite hydrogels were characterized. Physical performances of the ɛ-PL-HA hydrogels can be tailored by altering the mass ratio of Sr-HAp. The nanocomposite hydrogels revealed good stability against enzymatic degradation, which increased from 5 to 19 weeks with increasing the mass ratio of Sr-HAp from 40 % to 60 %. The loading of the Sr-HAp at relatively high mass ratios did not suppress the fast-acting and long-term antibacterial activity of the ɛ-PL-HA hydrogels against S. aureus and E. coli . The cell studies confirmed the cytocompatibility and pre-collagen I synthesis-promoting activity of the fabricated nanocomposite hydrogels. • Multifunctional Sr-HAp-loaded ɛ-PL-HA nanocomposite hydrogels were prepared. • The hydrogels possess injectability, self-healing ability, and structural integrity. • The hydrogels show long-term antibacterial activity against S. aureus and E. coli . • The hydrogels are effective against clinically isolated antibiotic-resistant bacteria. • The fabricated hydrogels exhibit cell viability and promote bone ECM production.