Materials & Design (Mar 2023)

Engineering mussel-inspired multifunctional nanocomposite hydrogels to orchestrate osteoimmune microenvironment and promote bone healing

  • Minhao Wu,
  • Ye Wang,
  • Huifan Liu,
  • Feixiang Chen,
  • Yufeng Zhang,
  • Ping Wu,
  • Zhouming Deng,
  • Lin Cai

Journal volume & issue
Vol. 227
p. 111705

Abstract

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The reconstruction of large bone defects by bioactive materials without exogenous cells, cytokines or growth factors remains a substantial clinical challenge. Herein, we present the rational design of injectable and adhesive (GMAD/LP) hydrogels composed of gelatin-methacryloyl (GelMA), dopamine-grafted alginate (AD), and polydopamine-functionalized Laponite (Lap@PDA) nanosheets that can act as osteoimmune regulators to engineer the pro-regenerative microenvironment for personalized bone regeneration. The as-fabricated GMAD/LP hydrogel with excellent tissue adhesion, self-healing, injectability, and improved mechanical strength can fill irregular bone defects in a minimally invasive manner. Moreover, the hydrogel exhibited outstanding osteogenic potential and osteoimmunomodulatory functions in vitro, significantly promoting the adhesion, proliferation, spreading, and osteogenic differentiation of bone mesenchymal stem cells (BMSCs), which was further augmented by hydrogel-induced macrophage M2-phenotype polarization and effective M2 macrophage-BMSC crosstalk. In vivo experiments in a cranial defect model demonstrated that the GMAD/LP hydrogel induced a reparative microenvironment similar to that in normal cranium, as characterized by an increased percentage of anti-inflammatory M2 macrophages and endogenous stem cells and high-level neovascularization, consequently accelerating bone healing. This strategy not only achieves a bioactive hydrogel for bone defect reconstruction but also provides a feasible methodology to recover injured bone tissue through integrated design with diverse functions.

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