Wafer-patterned, permeable, and stretchable liquid metal microelectrodes for implantable bioelectronics with chronic biocompatibility.

Implantable bioelectronics provide unprecedented opportunities for real-time and continuous monitoring of physiological signals of living bodies. Most bioelectronics adopt thin-film substrates such as polyimide and polydimethylsiloxane that exhibit high levels of flexibility and stretchability. However, the low permeability and relatively high modulus of these thin films hamper the long-term biocompatibility. In contrast, devices fabricated on porous substrates show the advantages of high permeability but suffer from low patterning density. Here, we report a wafer-scale patternable strategy for the high-resolution fabrication of supersoft, stretchable, and permeable liquid metal microelectrodes (µLMEs). We demonstrate 2-µm patterning capability, or an ultrahigh density of ~75,500 electrodes/cm2, of µLME arrays on a wafer-size (diameter, 100 mm) elastic fiber mat by photolithography. We implant the µLME array as a neural interface for high spatiotemporal mapping and intervention of electrocorticography signals of living rats. The implanted µLMEs have chronic biocompatibility over a period of eight months.

3D Bioprinting Photo-Crosslinkable Hydrogels for Bone and Cartilage Repair.

Three-dimensional (3D) bioprinting has become a promising strategy for bone manufacturing, with excellent control over geometry and microarchitectures of the scaffolds. The bioprinting ink for bone and cartilage engineering has thus become the key to developing 3D constructs for bone and cartilage defect repair. Maintaining the balance of cellular viability, drugs or cytokines' function, and mechanical integrity is critical for constructing 3D bone and/or cartilage scaffolds. Photo-crosslinkable hydrogel is one of the most promising materials in tissue engineering; it can respond to light and induce structural or morphological transition. The biocompatibility, easy fabrication, as well as controllable mechanical and degradation properties of photo-crosslinkable hydrogel can meet various requirements of the bone and cartilage scaffolds, which enable it to serve as an effective bio-ink for 3D bioprinting. Here, in this review, we first introduce commonly used photo-crosslinkable hydrogel materials and additives (such as nanomaterials, functional cells, and drugs/cytokine), and then discuss the applications of the 3D bioprinted photo-crosslinkable hydrogel scaffolds for bone and cartilage engineering. Finally, we conclude the review with future perspectives about the development of 3D bioprinting photo-crosslinkable hydrogels in bone and cartilage engineering.

A comparison of the characteristics of polyurethane-based sealers including various antimicrobial agents.

An obturation biomaterial that possess inherent antibacterial activity has been developed to create a tight seal for the root canal space in treatment. Novel castor oil-based polyurethane sealers composited with different proportions of silver phosphate or zinc oxide nanoparticles were synthesized to investigate the physicochemical properties, antibacterial effect on Enterococcus faecalis, and cytotoxicity on murine fibroblasts compared with commercially available products. The results showed that the physical properties of all of the polyurethane sealers could meet with the standards expected. The microdilatancy character of the polyurethane sealers was particularly preferable for the three dimensional obturation of root canal space. Compared with the silver-loaded polyurethane series, the zinc-loaded polyurethane series showed better antibacterial properties based on the contact mode. Analysis of the kinetics indicated that the setting process of the polyurethane sealers supported a first-order reaction and the setting process was highly effective, with more than 90% of the isocyanate groups participating in the setting reaction within 12 h. This is beneficial for the rapid consumption of monomers, efficiently avoiding inflammation. The in vitro results showed that the polyurethane sealers loaded with zinc oxide nanoparticles or 1 wt% silver phosphate were desirable for cell attachment and proliferation compared with the commercial sealers. In conclusion, the castor oil-based polyurethane-zinc sealers, especially PU-Zn5, present good physicochemical and antibacterial properties and cytocompatibility, and could be a promising candidate for application in the field of root canal treatment.

Effect of Microarc Oxidation-Treated Ti6Al4V Scaffold Following Low-Intensity Pulsed Ultrasound Stimulation on Osteogenic Cells in Vitro.

The porous Ti6Al4V alloy has emerged to solve the biomechanical mismatch between implant and bone as its tunable mechanical properties. Cell-surface interaction is related to numerous factors-the surface's chemical composition, morphological structure, and external effect. The microarc oxidation (MAO) method was employed in this study to improve the surface properties of scaffolds produced by Electron Beam Melting (EBM), and low-intensity pulse ultrasound (LIPUS) provides physical stimulation for cells in vitro. Although MAO-treated and untreated scaffolds shared the same three-dimensional (3D) structures, the former recreated a more affinity surface than the latter in the 3D room, which could stimulate cell adhesion, proliferation, and differentiation. Therefore, MG63 cells were represented with a stereoscopic cytoskeleton structure on the MAO-treated scaffold as numerous cellular filopodia/lamellipodia with rich extracellular matrix secretion, while flat and sheetlike cells were observed on the untreated scaffold. The expression of ALP, OCN, BMP2, Bmpr1a, and Runx2 were up-regulated by the MAO-treated scaffold; in addition, LIPUS stimulation effectively promoted cell proliferation and osteogenesis differentiation. In the future, the EBM-MAO strategy can be applied to prepare 3D hierarchical macro-/microstructure titanium implants for bone grafts, and LIPUS stimulation can be used as a therapeutic method simultaneously.

Elastomeric Polyurethane Foams Incorporated with Nanosized Hydroxyapatite Fillers for Plastic Reconstruction.

Plastic surgeons have long searched for the ideal materials to use in craniomaxillofacial reconstruction. The aim of this study was to obtain a novel porous elastomer based on designed aliphatic polyurethane (PU) and nanosized hydroxyapatite (n-HA) fillers for plastic reconstruction. The physicochemical properties of the prepared composite elastomer were characterized by infrared spectroscopy (IR), X-ray diffraction (XRD), scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX), transmission electron microscopy (TEM), thermal analysis, mechanical tests, and X-ray photoelectron spectroscopy (XPS). The results assessed by the dynamic mechanical analysis (DMA) demonstrated that the n-HA/PU compounded foams had a good elasticity, flexibility, and supporting strength. The homogenous dispersion of the n-HA fillers could be observed throughout the cross-linked PU matrix. The porous elastomer also showed a uniform pore structure and a resilience to hold against general press and tensile stress. In addition, the elastomeric foams showed no evidence of cytotoxicity and exhibited the ability to enhance cell proliferation and attachment when evaluated using rat-bone-marrow-derived mesenchymal stem cells (BMSCs). The animal experiments indicated that the porous elastomers could form a good integration with bone tissue. The presence of n-HA fillers promoted cell infiltration and tissue regeneration. The elastomeric and bioactive n-HA/PU composite foam could be a good candidate for future plastic reconstruction.

Injectable Gel Constructs with Regenerative and Anti-Infective Dual Effects Based on Assembled Chitosan Microspheres.

There is increasing demand for biomaterials that both assist with bone regeneration and have anti-infection qualities in clinical applications. To achieve this goal, chitosan microspheres with either positive or negative charges were fabricated and then assembled as a gel for bone healing. The positively charged chitosan microspheres (CSM; ∼35.5 µm) and negatively charged O-carboxymethyl chitosan microspheres (CMCSM; ∼13.5 µm) were loaded, respectively, with bone morphogenetic protein (BMP-2) and berberine (Bbr) via swollen encapsulation and physical adsorption without a significant change in the electric charges. The release kinetics of BMP-2 and Bbr from the microspheres were also studied in vitro. The results showed that the Bbr/CMCSM microsphere group possessed high antibacterial activity against Staphylococcus aureus; the BMP-2/CSM microsphere group also had excellent cytocompatibility and improved osteoinductivity with the assistance of BMP-2. The assembled gel group consisting of Bbr/CMCSM and BMP-2/CSM had a porous structure that allowed biological signal transfer and tissue infiltration and exhibited significantly enhanced bone reconstruction compared with that of the respective microsphere groups, which should result from the osteoconductivity of the porous structure and the osteoinduction of the BMP-2 growth factor. The oppositely charged microspheres and their assembled gel provide a promising prospect for making injectable tissue-engineered constructs with regenerative and anti-infective dual effects for biomedical applications.

Formulation and in vitro characterization of rifampicin-loaded porous poly (ε-caprolactone) microspheres for sustained skeletal delivery.

PURPOSE: Mycobacterium tuberculosis is a serious public health problem affecting hundreds of millions of elderly people worldwide, which is difficult to be treated by traditional methods because of the peculiarity of skeletal system and liver damage caused by high-dose administration. In this research, a porous drug release system has been attempted to encapsulate rifampicin (RIF) into poly (ε-caprolactone) (PCL) microspheres to improve the efficacy and benefit of anti-tuberculosis drug in skeletal system. MATERIALS AND METHODS: The microspheres prepared by two different methods, oil-in-oil (o/o) emulsion solvent evaporation method and oil-in-water (o/w) method, were characterized in terms of morphology, size, encapsulation efficiency, drug distribution, degradation, and crystallinity. RESULTS: The microspheres exhibited a porous structure with evenly drug distribution prepared by o/o emulsion solvent evaporation method, and their diameter ranged from 50.54 to 57.34 µm. The encapsulation efficiency was up to 61.86% when drug-loading content was only 1.51%, and showed a little decrease with the drug-loading content increasing. In vitro release studies revealed that the drug release from porous microspheres was controlled by non-Fickian diffusion, and almost 80% of the RIF were completely released after 10 days. The results of RIF-loaded microspheres on the antibacterial activity against Staphylococcus aureus proved that the porous microspheres had strong antibacterial ability. In addition, the polymer crystallinity had prominent influence on the degradation rate of microspheres regardless of the morphology. CONCLUSION: It was an efficient way to entrap slightly water-soluble drug like RIF into PCL by o/o emulsion solvent evaporation method with uniform drug distribution. The RIF-loaded porous PCL microspheres showed the combination of good antimicrobial properties and excellent cytocompatibility, and it could generate gentle environment by PCL slow degradation.