Directing Stem Cell Differentiation via Electrochemical Reversible Switching between Nanotubes and Nanotips of Polypyrrole Array.

Control of stem cell behaviors at solid biointerfaces is critical for stem-cell-based regeneration and generally achieved by engineering chemical composition, topography, and stiffness. However, the influence of dynamic stimuli at the nanoscale from solid biointerfaces on stem cell fate remains unclear. Herein, we show that electrochemical switching of a polypyrrole (Ppy) array between nanotubes and nanotips can alter surface adhesion, which can strongly influence mechanotransduction activation and guide differentiation of mesenchymal stem cells (MSCs). The Ppy array, prepared via template-free electrochemical polymerization, can be reversibly switched between highly adhesive hydrophobic nanotubes and poorly adhesive hydrophilic nanotips through an electrochemical oxidation/reduction process, resulting in dynamic attachment and detachment to MSCs at the nanoscale. Multicyclic attachment/detachment of the Ppy array to MSCs can activate intracellular mechanotransduction and osteogenic differentiation independent of surface stiffness and chemical induction. This smart surface, permitting transduction of nanoscaled dynamic physical inputs into biological outputs, provides an alternative to classical cell culture substrates for regulating stem cell fate commitment. This study represents a general strategy to explore nanoscaled interactions between stem cells and stimuli-responsive surfaces.

Nanocomposite Membranes Enhance Bone Regeneration Through Restoring Physiological Electric Microenvironment.

Physiological electric potential is well-known for its indispensable role in maintaining bone volume and quality. Although implanted biomaterials simulating structural, morphological, mechanical, and chemical properties of natural tissue or organ has been introduced in the field of bone regeneration, the concept of restoring physiological electric microenvironment remains ignored in biomaterials design. In this work, a flexible nanocomposite membrane mimicking the endogenous electric potential is fabricated to explore its bone defect repair efficiency. BaTiO3 nanoparticles (BTO NPs) were first coated with polydopamine. Then the composite membranes are fabricated with homogeneous distribution of Dopa@BTO NPs in poly(vinylidene fluoridetrifluoroethylene) (P(VDF-TrFE)) matrix. The surface potential of the nanocomposite membranes could be tuned up to -76.8 mV by optimizing the composition ratio and corona poling treatment, which conform to the level of endogenous biopotential. Remarkably, the surface potential of polarized nanocomposite membranes exhibited a dramatic stability with more than half of original surface potential remained up to 12 weeks in the condition of bone defect. In vitro, the membranes encouraged bone marrow mesenchymal stem cells (BM-MSCs) activity and osteogenic differentiation. In vivo, the membranes sustainably maintained the electric microenvironment giving rise to rapid bone regeneration and complete mature bone-structure formation. Our findings evidence that physiological electric potential repair should be paid sufficient attention in biomaterials design, and this concept might provide an innovative and well-suited strategy for bone regenerative therapies.

Effects of deer age on the physicochemical properties of deproteinized antler cancellous bone: an approach to optimize osteoconductivity of bone graft.

Inorganic bone xenograft materials have recently found extensive surgical application in the clinic. Previously we have demonstrated that calcinated antler cancellous bone (CACB) has great potential for bone defect repair, due to the similar structure and composition compared with human bone. However, the effect of intrinsic material characteristics, particularly deer age, on the physicochemical and biological properties of CACB scaffolds has not been clarified. The aim of this study is to investigate the structure, composition and in vitro solubility of CACB scaffolds derived from deer of varying ages, including young (CACB-Y), middle-aged (CACB-M), and old (CACB-O) deer, and to determine subsequent biological performance. Microstructural analyses showed looser crystal arrangement and lower porosity in CACB-M compared to CACB-Y and CACB-O. Phase-structure analysis showed that CACB-M had the largest crystal size. Component characterization results showed that CACB-M had the most carbonated substitute and the highest content of trace elements (Na, Fe). The in vitro solubility test showed that CACB-M had the fastest dissolution and apatite deposition rates with new crystalline phases. In addition, CACB-M could be conducive for attachment, proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells in vitro, as well as conducive for bone regeneration in vivo. These findings indicate that animal age should be seriously considered as a key parameter in optimizing the physicochemical and biological properties of deproteinized antler cancellous bone substitutes for bone regeneration applications.