Integrating Porous Silicon Nanoneedles within Medical Devices for Nucleic Acid Nanoinjection.

Porous silicon nanoneedles can interface with cells and tissues with minimal perturbation for high-throughput intracellular delivery and biosensing. Typically, nanoneedle devices are rigid, flat, and opaque, which limits their use for topical applications in the clinic. We have developed a robust, rapid, and precise substrate transfer approach to incorporate nanoneedles within diverse substrates of arbitrary composition, flexibility, curvature, transparency, and biodegradability. With this approach, we integrated nanoneedles on medically relevant elastomers, hydrogels, plastics, medical bandages, catheter tubes, and contact lenses. The integration retains the mechanical properties and transfection efficiency of the nanoneedles. Transparent devices enable the live monitoring of cell-nanoneedle interactions. Flexible devices interface with tissues for efficient, uniform, and sustained topical delivery of nucleic acids ex vivo and in vivo. The versatility of this approach highlights the opportunity to integrate nanoneedles within existing medical devices to develop advanced platforms for topical delivery and biosensing.

Quantifying error introduced by iterative closest point image registration.

OBJECTIVES: The aim of this paper was to quantify the analysis error introduced by iterative closest point (ICP) image registration. We also investigated whether a subsequent subtraction process can reduce process error. METHODS: We tested metrology and two 3D inspection software using calibration standards at 0.39 µm, and 2.64 µm and mathematically perfect defects (softgauges) at 2 and 20 µm, on free form surfaces of increasing complexity and area, both with and without registration. Errors were calculated in percentage relative to the size of the defect being measured. Data were analysed in GraphPad Prism 9, normal and two-way ANOVA with post-hoc Tukey's was applied. Significance was inferred at p < 0.05. RESULTS: Using ICP registration introduced errors from 0 % to 15.63 % of the defect size depending on the surface complexity and size of the defect. Significant differences were observed in analysis measurements between metrology and 3D inspection software and within different 3D inspection software, however, one did not show clear superiority over another. Even in the absence of registration, defects at 0.39 µm, and 2.64 µm produced substantial measurement error (13.39-77.50 % of defect size) when using 3D inspection software. Adding an additional data subtraction process reduced registration error to negligible levels (<1 % independent of surface complexity or area). CONCLUSIONS: Commercial 3D inspection software introduces error during direct measurements below 3 µm. When using an ICP registration, errors over 15 % of the defect size can be introduced regardless of the accuracy of adjacent registration surfaces. Analysis output between software are not consistently repeatable or comparable and do not utilise ISO standards. Subtracting the datasets and analysing the residual difference reduced error to negligible levels. CLINICAL SIGNIFICANCE: This paper quantifies the significant errors and inconsistencies introduced during the registration process even when 3D datasets are true and precise. This may impact on research diagnostics and clinical performance. An additional data processing step of scan subtraction can reduce this error but increases computational complexity.

A rapidly magnetically assembled stem cell microtissue with "hamburger" architecture and enhanced vascularization capacity.

With the development of magnetic manipulation technology based on magnetic nanoparticles (MNPs), scaffold-free microtissues can be constructed utilizing the magnetic attraction of MNP-labeled cells. The rapid in vitro construction and in vivo vascularization of microtissues with complex hierarchical architectures are of great importance to the viability and function of stem cell microtissues. Endothelial cells are indispensable for the formation of blood vessels and can be used in the prevascularization of engineered tissue constructs. Herein, safe and rapid magnetic labeling of cells was achieved by incubation with MNPs for 1 h, and ultrathick scaffold-free microtissues with different sophisticated architectures were rapidly assembled, layer by layer, in 5 min intervals. The in vivo transplantation results showed that in a stem cell microtissue with trisection architecture, the two separated human umbilical vein endothelial cell (HUVEC) layers would spontaneously extend to the stem cell layers and connect with each other to form a spatial network of functional blood vessels, which anastomosed with the host vasculature. The "hamburger" architecture of stem cell microtissues with separated HUVEC layers could promote vascularization and stem cell survival. This study will contribute to the construction and application of structural and functional tissues or organs in the future.

The Translation from In Vitro Bioactive Ion Concentration Screening to In Vivo Application for Preventing Peri-implantitis.

Peri-implantitis is a typical pathological condition characterized by the destructive inflammation in the soft tissue and the progressive loss of supporting bones. As the current effective treatments and preventive measures are inconsistent and unpredictable, the use of biomaterials as carriers of bioactive ion coatings is a promising approach. However, the translation from lab to large-scale production and clinical applications is difficult due to a technology barrier. Determining the effective dosage of each ion to achieve an in vivo application of the in vitro screening is challenging. Here, we selected zinc and strontium ions to provide multiple effects on antibacterial activity and osteogenesis. The optimal coating with effective release concentrations of the two ions was obtained after the two-step screening from in vitro testing. The results showed that this type of in vivo bioactive ion usage leads to an enhanced osseointegration during the immediate implantation in a periodontitis-affected environment and prevents soft tissue inflammation and bone resorption in an inflammatory environment. The new biologically active ion screening method could verify the effectiveness of this clinical translation and its potential for large-scale production and could determine the effective dosage of each ion for a specific application.

Graphene oxide-coated porous titanium for pulp sealing: an antibacterial and dentino-inductive restorative material.

Pulp treatment techniques such as pulp capping, pulpotomy and pulp regeneration are all based on the principle of preserving vital pulp. However, specific dental restorative materials that can simultaneously protect pulp vitality and repair occlusal morphology have not been developed thus far. Traditional pulp capping materials cannot be used as dental restorative materials due to their long-term solubility and poor mechanical behavior. Titanium (Ti) is used extensively in dentistry and is regarded as a promising material for pulp sealing because of its favorable biocompatibility, processability and mechanical properties. Originally, we proposed the concept of "odontointegration", which represents direct dentin-like mineralization contact between pulp and the surface of the pulp sealing material; herein, we report the fabrication of a novel antibacterial and dentino-inductive material via micro-arc oxidation (MAO), incorporating self-assembled graphene oxide (GO) for Ti surface modification. The hierarchical micro/nanoporous structure of the MAO coating provides a suitable microenvironment for odontogenic differentiation of human dental pulp stem cells, and GO loading contributes to antibacterial activity. Scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy and Raman spectroscopy were employed for structure and elemental analysis. In vitro studies, including cell adhesion, Live/Dead and CCK-8 assays, alkaline phosphatase activity and calcium deposition assay, real-time polymerase chain reaction, western blot analysis and immunofluorescence staining were used to examine cell adhesion, viability, proliferation, mineralization, and odontogenic differentiation ability. Antibacterial properties against Streptococcus mutans were analyzed by SEM, spread plate, Live/Dead and Alamar blue tests. The Ti-MAO-1.0 mg mL-1 GO group exhibited excellent cell adhesion, odontoblast differentiation, mineralization, and antibacterial ability, which are beneficial to odontointegration.

In situ gas foaming based on magnesium particle degradation: A novel approach to fabricate injectable macroporous hydrogels.

Injectable hydrogels are attractive biomaterials for cell delivery in tissue engineering. However, the in vivo viability of transplanted cells remains limited. Typically, macroporous structures constructed in hydrogels are utilized to enhance oxygen and nutrients diffusion for cell survival and to promote integration between the material and host tissue. A new gas-foaming method to generate pores was proposed by directly adding Mg particles into cell-laden hydrogel solutions, taking advantage of the H2 gas formed during the degradation of Mg. The optimization design of the size and amount of Mg particles added into the hydrogels was investigated. Improved cell viability and proliferation were demonstrated in the group with Mg particles. Additionally, Mg2+ ions generated during Mg degradation facilitated the osteogenic differentiation of stem cells encapsulated in hydrogels. Extensive vascularized bone regeneration in the femoral defects of rats revealed that the use of Mg particles as the foaming agent is feasible, endowing injectable hydrogels with optimized porosity and enhanced bioactivity, and providing a new strategy for future designs of porous hydrogels in tissue engineering.