Metabolically activated energetic materials mediate cellular anabolism for bone regeneration.

Area of Science:

• Biomaterials Science
• Cellular Metabolism
• Regenerative Medicine

Background:

• Cellular energy metabolism activation by scaffolds is crucial for tissue regeneration but poorly understood.
• Engineered scaffolds that modulate cellular metabolism can address challenges in therapeutic bone regeneration.

Purpose of the Study:

• To investigate the role of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] and its degradation product 3-hydroxybutyrate (3HB) in cellular anabolism and osteogenesis.
• To evaluate the efficacy of P(3HB-co-4HB) scaffolds and 3HB in promoting bone regeneration in vitro and in vivo.

Main Methods:

• Biosynthesis of P(3HB-co-4HB) and assessment of its degradation product 3HB.
• In vitro studies on human bone marrow-derived mesenchymal stem cells (hBMSCs) measuring ATP production, mitochondrial membrane potential, and capillary-like tube formation.
• Analysis of tricarboxylic acid (TCA) cycle metabolites and citrate levels.
• In vivo studies using ovariectomized rats to assess bone mass and rat cranial defect models for bone regeneration.

Main Results:

• 3HB significantly increased in vitro ATP production, mitochondrial membrane potential, and capillary-like tube formation in hBMSCs.
• 3HB elevated TCA cycle citrate levels, facilitating citrate-containing apatite synthesis during osteogenesis.
• In vivo, 3HB administration increased bone mass in osteoporotic rats, and P(3HB-co-4HB) scaffolds enhanced vascularized bone regeneration in cranial defects.

Conclusions:

• 3HB acts as an endogenous bioenergetic fuel promoting hBMSC osteogenesis through metabolic activation.
• P(3HB-co-4HB) scaffolds offer a promising strategy for enhancing bone regeneration via metabolic modulation.
• These findings reveal a novel role for 3HB in osteogenesis and highlight the potential of metabolically active scaffolds in regenerative medicine.