Biomineralized Piezoelectrically Active Scaffolds for Inducing Osteogenic Differentiation.

There is an endogenous electric field in living organisms, which plays a vital role in the development and regeneration of bone tissue. Therefore, self-powered piezoelectric material for bone repair has become hot research in recent years. However, the current piezoelectric materials for tissue regeneration still have the shortcomings of lack of biological activity and three-dimensional structure. Here, we proposed a three-dimensional polyurethane foam (PUF) scaffold coated with piezoelectric poly (vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) and modified by a calcium phosphate (CaP) mineralized coating. The preferred scaffold has an open circuit voltage and short circuit current output of 5 V and 200 nA. Combining the physical and chemical properties of the CaP coating, the piezoelectric signal of PVDF-HFP and the three-dimensional structure of PUF, the scaffold exhibits superior promotion of cell osteogenic differentiation and ectopic bone formation in vivo. The mechanism is attributed to an increase in intracellular Ca2+ levels in response to chemical and piezoelectric stimulation with the material. This research not only paves the way for the application of piezoelectric scaffolds to stimulate osteoblasts differentiation in situ, but also lays the foundation for the clinical treatment of long-term osteoporosis.

Shear Flow-Assembled Janus Membrane with Bifunctional Osteogenic and Antibacterial Effects for Guided Bone Regeneration.

Guided bone regeneration (GBR) membranes that reside at the interface between the bone and soft tissues for bone repair attract increasing attention, but currently developed GBR membranes suffer from relatively poor osteogenic and antibacterial effects as well as limited mechanical property and biodegradability. We present here the design and fabrication of a bifunctional Janus GBR membrane based on a shear flow-driven layer by a layer self-assembly approach. The Janus GBR membrane comprises a calcium phosphate-collagen/polyethylene glycol (CaP@COL/PEG) layer and a chitosan/poly(acrylic acid) (CHI/PAA) layer on different sides of a collagen membrane to form a sandwich structure. The membrane exhibits good mechanical stability and tailored biodegradability. It is found that the CaP@COL/PEG layer and CHI/PAA layer contribute to the osteogenic differentiation and antibacterial function, respectively. In comparison with the control group, the Janus GBR membrane displays a 2.52-time and 1.84-time enhancement in respective volume and density of newly generated bone. The greatly improved bone repair ability of the Janus GBR membrane is further confirmed through histological analysis, and it has great potential for practical applications in bone tissue engineering.

A healing promoting wound dressing with tailor-made antibacterial potency employing piezocatalytic processes in multi-functional nanocomposites.

Developing a novel antibiotics-free antibacterial strategy is essential for minimizing bacterial resistance. Materials that not only kill bacteria but also promote tissue healing are especially challenging to achieve. Inspired by chemical conversion processes in living organisms, we develop a piezoelectrically active antibacterial device that converts ambient O2 and H2O to ROS by piezocatalytic processes. The device is achieved by mounting nanoscopic polypyrrole/carbon nanotube catalyst multilayers onto piezoelectric-dielectric films. Under stimuli by a hand-held massage device, the sterilizing rates for S. aureus and E. coli reach 84.11% and 94.85% after 10 minutes of operation, respectively. The antibacterial substrate at the same time preserves and releases drugs and presents negligible cytotoxicity. Animal experiments demonstrate that daily treatment for 10 minutes using the device effectively accelerates the healing of infected wounds on the backs of mice, promoting hair follicle generation and collagen deposition. We believe that this report provides a novel design approach for antibacterial strategies in medical treatment.

Bioactive NAD+ Regeneration Promoted by Multimetallic Nanoparticles Based on Graphene-Polymer Nanolayers.

The concentration of nicotinamide adenine dinucleotide oxidized form (NAD+) changes during aging, and the production of NAD+ can significantly affect both health span and life span. However, it is still of great challenge to regenerate NAD+ from its precursors. Herein, we introduce a method to prepare multimetallic nanoparticles (including Au, Pt, Cu, and MgO) that can efficiently promote the conversion of NADH to NAD+. The nanoparticles are made by mixing reduced graphene oxide-polyethyleneimine-polyacrylic acid nano-films with metallic salts, where four different metal ions are reduced and grow at the surface of the nanolayers. The morphology, size, and growth rate of nanoparticles can be controlled by adding surfactants, applying an electric field, and so forth. Our multimetallic nanoparticles exhibit excellent catalytic performance that a complete conversion of NADH to NAD+ can be finished in 3 min without introducing additional oxygen. This work presents a way for the preparation of multimetallic nanoparticles to promote NAD+ regeneration, which shows great promise for the future design of high-performance materials for antiaging.

Biofriendly molecular and protein release substrate with integrated piezoelectric motivation and anti-oxidative stress capabilities.

Self-powered piezoelectrically active molecular or protein delivery devices have provoked great interest in recent years. However, electric fields used to promote delivery or healing may also induce the redox of water or oxygen to generate reactive oxygen species (ROS) and bring unintended oxidative pressure to the organism and harm biological functions. In addition, protein molecules are easily inactivated in the polymer reservoir matrix due to the pull of strong electrostatic effects. In this study, a multifunctional molecular delivery substrate was fabricated by integrating a piezoelectric-dielectric polymeric substrate, nanoscopic polyelectrolyte films and in-film deposited biomimetic porous CaP coating. The piezoelectric substrate promoted molecular release, and the mineralized coating effectively stored molecules or proteins and simultaneously eliminated ROS, reducing the oxidative stress response generated by oxidative pressure. The present work opens a new way for the development of multifunctional and biofriendly drug delivery devices.

A self-powered delivery substrate boosts active enzyme delivery in response to human movements.

Stimulated drug releases in response to human movements are highly appealing in medical therapy and various daily uses. However, the design of a mechanically responsive substrate that presents high delivery capacities and can also preserve the activities of sensitive molecules such as enzymes is still challenging. Taking advantage of the recent development in effective piezoelectric flexible films and in molecular delivery devices, we propose a composite delivery substrate that preserves enzyme activities and enhances molecular delivery in response to human movements such as finger presses or massages. The substrate is achieved by combining two parts, which are the energy converting unit and the molecular loading and releasing unit. The energy converting unit is a piezoelectric-dielectric flexible composite film that produces enhanced electricity and preserves the electricity longer compared to a pure piezoelectric polymer. The molecular delivery unit is a layer-by-layer multilayer containing mesoporous silica particles that are assembled at pH 9 but used in neutral solutions. The releases of molecules including small molecules, peptides, and proteins are all accelerated in response to finger presses irrespective of the signs or densities of their charges. More importantly, the enzyme CAT preserves its activity after release from the composite substrates, meaning that the CAT-loaded (PAH/MS)n(PAH/DAS)n@rGO-TFB/PVDF-HFP composite substrate holds promise as a self-powered soothing pad that effectively removes residue H2O2.