Oxidation-responsive, settable bone substitute composites for regenerating critically-sized bone defects

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Polymer Chemistry

Background:

• Critically-sized bone defects pose significant clinical challenges, often requiring implants for healing.
• Current synthetic bone implants like poly(methyl methacrylate) (PMMA) have limitations including poor biodegradability and osseointegration.
• Existing biodegradable polyesters (PCL, PLGA) face challenges in matching degradation rates to bone regeneration.

Purpose of the Study:

• To develop novel, cell-degradable polymer/hydroxyapatite composites for *in situ* bone void filling.
• To engineer implants that resorb in response to biologically produced reactive oxygen species (ROS).
• To evaluate the efficacy of these new bone substitutes in a critically-sized bone defect model.

Main Methods:

• Formulation of a cell-degradable polymer using a thioketal (TK) linker and a tri-functional epoxy for *in situ* curing.
• Investigating the degradation profiles of TK composites in varying concentrations of ROS.
• Assessing the biocompatibility and bone regeneration capacity of TK composites in a rat skull defect model compared to PMMA.

Main Results:

• The developed TK bone substitutes exhibited tunable curing and mechanical properties.
• Implants demonstrated selective degradation in a dose-dependent manner in response to ROS.
• TK composites were non-cytotoxic and significantly enhanced bone regeneration compared to PMMA in a rat model.

Conclusions:

• Cell-degradable TK polymer/hydroxyapatite composites represent a promising advancement in bone void fillers.
• These novel materials offer tunable degradation and enhanced bone regeneration capabilities.
• TK bone substitutes show significant therapeutic potential over conventional polymeric bone implants.