Bioenergetic-active materials enhance tissue regeneration by modulating cellular metabolic state


Cellular bioenergetics (CBE) plays a critical role in tissue regeneration. Physiologically, an enhanced metabolic state facilitates anabolic biosynthesis and mitosis to accelerate regeneration. However, the development of approaches to reprogram CBE, toward the treatment of substantial tissue injuries, has been limited thus far.

Here, we show that induced repair in a rabbit model of weight-bearing bone defects is greatly enhanced using a bioenergetic-active material (BAM) scaffold compared to commercialized poly(lactic acid) and calcium phosphate ceramic scaffolds. This material was composed of energy-active units that can be released in a sustained degradation-mediated fashion once implanted.

By establishing an intramitochondrial metabolic bypass, the internalized energy-active units significantly elevate mitochondrial membrane potential (ΔΨm) to supply increased bioenergetic levels and accelerate bone formation. The ready-to-use material developed here represents a highly efficient and easy-to-implement therapeutic approach toward tissue regeneration, with promise for bench-to-bedside translation.

Energy metabolism serves a vital role in tissue repair and regeneration. Adenosine triphosphate (ATP) represents the principal source of cellular energy with roles in numerous biological processes. It has been suggested that engineering the modulation of oxidative metabolism to increase cellular ATP levels could help address the high energetic requirements associated with enhanced anabolic biosynthesis, mitosis, and migration involved in tissue repair/regeneration (5).

Recent progress in cellular bioenergetics (CBE) has highlighted the potential of approaches that allow the delivery of bioenergy for therapeutic purposes (610); however, these applications only provide benefits in in vitro models or relatively thin superficial tissues such as skin when continuously administered. To date, a three-dimensional (3D) scaffold with long-term bioenergetics effects that can stimulate the repair of critical size defects in complex tissues such as bone remains elusive.

This is in large part the result of an inability to improve the stability and associated activity of ATP with the use of existing scaffold fabrication techniques, concurrent with the susceptibility of ATP to the physiological milieu.

Science Advances  25 Mar 2020:
Vol. 6, no. 13, eaay7608
DOI: 10.1126/sciadv.aay7608