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.

A high-strength biodegradable thermoset polymer for internal fixation bone screws: Preparation, in vitro and in vivo evaluation.

Thermoset polymers synthesized from the polycondensation of glycerol with biocompatible diacids represent a promising class of absorbable materials for biomedical applications. However, the utility of these polymers for bone fixation devices is hampered due to the lack of mechanical strength. Herein we synthesized a high-strength thermoset polymer, poly(glycerol-succinate) (PGS), via a catalyst-free and solvent-free reaction. The bending strength of PGS reaches 122.01 ±â€¯8.82 MPa, signifying its great potential for fixation devices. The degradation property of the polymer can be tuned by adjusting the monomer ratio and reaction time. Bone screws based on the PGS polymer were successfully manufactured using a lathe. In vitro evaluation showed the PGS polymer was able to well support cell adhesion and proliferation. In vivo evaluation using a rat subcutaneous implantation model showed that the inflammatory response to the polymer was mild. After the PGS screws were implanted in the rabbit femoral condyle for 12 weeks, micro-computed tomography (micro-CT) and histological analysis revealed that the screws achieved good osseointegration. Consequently, the polymer developed in current study can serve as internal fixation devices due to the proper mechanical strength, excellent biocompatibility, and feasibility of manufacturing screws.

In Vitro and in Vivo Mechanism of Bone Tumor Inhibition by Selenium-Doped Bone Mineral Nanoparticles.

Biocompatible tissue-borne crystalline nanoparticles releasing anticancer therapeutic inorganic elements are intriguing therapeutics holding the promise for both tissue repair and cancer therapy. However, how the therapeutic inorganic elements released from the lattice of such nanoparticles induce tumor inhibition remains unclear. Here we use selenium-doped hydroxyapatite nanoparticles (Se-HANs), which could potentially fill the bone defect generated from bone tumor removal while killing residual tumor cells, as an example to study the mechanism by which selenium released from the lattice of Se-HANs induces apoptosis of bone cancer cells in vitro and inhibits the growth of bone tumors in vivo. We found that Se-HANs induced apoptosis of tumor cells by an inherent caspase-dependent apoptosis pathway synergistically orchestrated with the generation of reactive oxygen species. Such mechanism was further validated by in vivo animal evaluation in which Se-HANs tremendously induced tumor apoptosis to inhibit tumor growth while reducing systemic toxicity. Our work proposes a feasible paradigm toward the design of tissue-repairing inorganic nanoparticles that bear therapeutic ions in the lattice and can release them in vivo for inhibiting tumor formation.

Shaping functional nano-objects by 3D confined supramolecular assembly.

Nano-objects are generated through 3D confined supramolecular assembly, followed by a sequential disintegration by rupturing the hydrogen bonding. The shape of the nano-objects is tunable, ranging from nano-disc, nano-cup, to nano-toroid. The nano-objects are pH-responsive. Functional materials for example inorganic or metal nanoparticles are easily complexed onto the external surface, to extend both composition and microstructure of the nano-objects.