Injectable porous nanocomposite microgel assemblies engineered via a triple-dynamic crosslinking strategy for...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Nanotechnology

Background:

• Critical-sized bone defects pose significant clinical challenges.
• Existing microgel assembly strategies have limitations like UV light exposure, slow crosslinking, and poor mechanical strength.
• Organic-inorganic composites for bone regeneration struggle with particle distribution and size control.

Purpose of the Study:

• To develop an injectable, self-healing, porous nanocomposite microgel assembly for enhanced vascularized bone regeneration.
• To address limitations of current bone regenerative materials through a novel triple-dynamic crosslinking strategy.
• To create a multifunctional material with improved mechanical properties and controlled release of therapeutic ions.

Main Methods:

• Fabrication of a bisphosphonate-magnesium/hyaluronic acid-Poly (L-glutamate) (BP-Mg/HA-PLG) nanocomposite microgel assembly.
• Utilized a triple-dynamic crosslinking strategy involving BP-Mg chelation, host-guest interaction, and Schiff base linkage.
• Evaluated the material's properties, including injectability, self-healing, mechanical strength, nanoparticle distribution, and ion release *in vitro* and *in vivo*.

Main Results:

• The developed BP-Mg/HA-PLG microgel assembly demonstrated rapid reassembly, robust mechanics, and excellent self-healing capabilities.
• Achieved uniform in-situ formation of BP-Mg nanoparticles, enhancing mechanical strength and enabling sustained release of bisphosphonate (BP) and magnesium ions (Mg2+).
• *In vitro* studies showed synergistic pro-angiogenic, anti-osteoclastogenic, and pro-osteogenic effects, while *in vivo* studies in a rat model significantly promoted bone regeneration within 8 weeks.

Conclusions:

• The injectable, self-healing BP-Mg/HA-PLG nanocomposite microgel assembly offers a promising multifunctional solution for vascularized bone regeneration.
• The triple-dynamic crosslinking strategy effectively overcomes limitations of previous bone repair materials.
• This novel material presents a translatable approach to address critical challenges in bone defect repair.