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

Abstract

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.

Biodegradable hollow mesoporous organosilica nanotheranostics (HMON) for multi-mode imaging and mild photo-therapeutic-induced mitochondrial damage on gastric cancer

“…The as-prepared HMON showed speci c strong and broad peaks at 2927.32 cm -1 and 2855.28 cm -1 (attributed to -CH 2 ) [29], which represented the covalent grafting of C18PMH-mPEG chains onto the surface of HMON, compared to non-PEGylation HMON. Meanwhile, new peak at 627.03 cm -1 (attributed to Cu-S) was also observed in HMON@CuS and HMON@CuS/Gd [30].…”

A review of biomimetic scaffolds for bone regeneration: Toward a cell‐free strategy

“…Through a series of experiments, both in vitro and in vivo results demonstrated that the degradation products instead of retaining the chemical or physical features of the scaffold materials may enhance bone regeneration via bioenergetic metabolism pathways. Moreover, the underlying mechanism of the promotion of repair by BAM may be that the elevated content of extracellular ATP can lead to a signaling cascade for enhanced bone repair, referring to the upregulation of purine receptors and the transduction of downstream signals via c‐Jun at the level of the gene 28 . In conclusion, the development of bioenergetic materials described here offer an uncomplicated and highly effective way to regulate the energetic demands at the early stages of bone repair.…”

“…Lastly, energy-driven, photothermally modified, thermodynamically controlled, and photoluminescent biodegradable materials have been prepared by researchers [28][29][30]. Tissue regeneration is dependent upon cellular bioenergetics (CBE) which, within bioenergetic-active material (BAM) scaffolds, promote mitochondrial membrane potential (ΔΨm) to provide elevated bioenergetic levels and further accelerate bone repair [28].…”

“…Lastly, energy-driven, photothermally modified, thermodynamically controlled, and photoluminescent biodegradable materials have been prepared by researchers [28][29][30]. Tissue regeneration is dependent upon cellular bioenergetics (CBE) which, within bioenergetic-active material (BAM) scaffolds, promote mitochondrial membrane potential (ΔΨm) to provide elevated bioenergetic levels and further accelerate bone repair [28]. For the simultaneous treatment of osteosarcoma and tissue regeneration in clinical terms, an innovative multifunctional scaffold with temperature-controlled characteristics has been reported which can efficiently eliminate human osteosarcoma cells at 48℃, while enhancing osteogenesis of BMSCs at a temperature of 42 ± 0.5℃ using 808-nm near-infrared (NIR) light irradiation [30].…”

Biodegradable hollow mesoporous organosilica nanotheranostics (HMON) for multi-mode imaging and mild photo-therapeutic-induced mitochondrial damage on gastric cancer

“…The as-prepared HMON showed specific strong and broad peaks at 2927.32 cm −1 and 2855.28 cm −1 (attributed to -CH 2 ) [29], which represented the covalent grafting of C18PMH-mPEG chains onto the surface of HMON, compared to non-PEGylation HMON. Meanwhile, new peak at 627.03 cm −1 (attributed to Cu-S) was also observed in HMON@CuS and HMON@ CuS/Gd [30].…”