The peripheral nervous system (PNS) is an attractive target for modulation of afferent input (e.g., nociceptive input signaling tissue damage) to the central nervous system. To advance mechanistic understanding of PNS neural encoding and modulation requires single-unit recordings from individual peripheral neurons or axons. This is challenged by multiple connective tissue layers surrounding peripheral nerve fibers that prevent electrical recordings by existing electrodes or electrode arrays. In this study, we developed a novel microelectrode array (MEA) via silicon-based microfabrication that consists of 5 parallel hydrophilic gold electrodes surrounded by silanized hydrophobic surfaces. This novel hydrophilic/hydrophobic surface pattern guides the peripheral nerve filaments to self-align towards the hydrophilic electrodes, which dramatically reduces the technical challenges in conducting single-unit recordings. We validated our MEA by recording simultaneous single-unit action potentials from individual axons in mouse sciatic nerves, including both myelinated A-fibers and unmyelinated C-fibers. We confirmed that our recordings were single units from individual axons by increasing nerve trunk electrical stimulus intensity, which did not alter the spike shape or amplitude. By reducing the technical challenges, our novel MEA will likely allow peripheral single-unit recordings to be adopted by a larger research community and thus expedite our mechanistic understanding of peripheral neural encoding and modulation.

With a global prevalence of more than 2 million graft procedures per year, bone grafts are one of the most common transplants. [1][2][3][4][5] Small bone defects can be restored naturally, while large defects created by severe trauma, accidents, or tissue resection are unable to heal on their own. [6] As a rigid organ in humans and live animals, bone supports and protects different organs, tissues, and facilitates the mobility of the body. [7,8] These unique applications of bone are mainly attributed to the hierarchical architecture of bone, which mainly consists of the soft collagen protein and stiffer apatite mineral. [9] The overall stiffness of bone is primarily controlled by the natural mineral content as well as collagen to mineral ratio. [7,10] The mechanism of bone regeneration can be categorized as direct or indirect healing. [11] The size of fracture is one of the important factors that affects the bone healing mechanism. Direct bone healing mainly starts when a small and narrow (≤0.1 mm) fracture occurs, and the site of a fracture is rigidly stabilized. During direct bone healing, the small gap is covered directly by continuous ossification, following Haversian remodeling in a serial order. [12] Larger defects mostly heal by the indirect bone healing via various parallel events, such as blood clotting, inflammatory response, fibrocartilage callus formation, intramembranous and endochondral ossification, and results in bone remodeling. [11,12] A critical size defect is defined as the minimum defect dimension which is incapable of repairing without intervention. Per Food and Drug Administration (FDA) recognized standard ASTM F2721, in a critical size defect, the length of defect is at least 1.5-2 times the diameter of the selected bone. Critically sized defects can overwhelm the tissue regeneration capacity and lead to permanent disabilities. [13,14] Thus, surgical interventions are needed for the treatment of critically sized defects (Figure 1).Bone mimetic grafts, with hierarchical structure, and effective functionality could be engineered by merging suitable biomaterials, [7] cells, [15] and bioactive agents. [16] To design biomimetic bone scaffolds, a combination of nano-/microtechnologies with macrotechnologies is required. [17] Although many technologies have been developed for bone tissue engineering incorporating

In this research, we first performed a computational fluid dynamics (CFD) study of the effects of the inlet solution's concentration and channel height to produce microfibres in a microfluidic system by COMSOL 5.3 to find the optimum ratio of sheath to core flow rate. It proved that the ratio of sheath to core flow rate should considered more than 1 to have jet regime in the microchannel. The results show that the level of Ca2+ diffusion in an alginate inlet solution has a direct and reverse correlation with the initial sheath solution's concentration and initial core solution's concentration, respectively. Secondly, the response surface methodology (RSM) in Design Expert 7.0.0, was used to investigate the effects of alginate and calcium chloride flow rates on the average microfibres' diameter. We found that the best value of Ca2+ concentration in the core flow to produce fine appropriate microfibres is 150 mol/m3. Then, we developed a microchip using lithography, in which a silicon wafer was etched vertically instead of using a SU‐8 photo resist on glass, causing a significant improvement in the quality of channels and mould. The SEM images revealed low roughness of fabricated micro‐channels, which was eye‐catching. Eventually, the possibility of using the microfibres as polymeric carriers for hydrophobic drugs was investigated, and then fluorescent microscopic images of the loaded fibres indicated that the drug is well‐loaded onto the fibres: the results are promising.

Microneedles have recently emerged as a powerful tool for minimally invasive drug delivery and body fluid sampling. To date, high‐resolution fabrication of microneedle arrays (MNAs) is mostly achieved by the utilization of sophisticated facilities and expertise. Particularly, hollow microneedles have usually been manufactured in cleanrooms out of silicon, resin, or metallic materials. Such strategies do not support the fabrication of microneedles from biocompatible/biodegradable materials and limit the capability of multimodal drug delivery for the controlled release of different therapeutics through a combination of injection and sustained diffusion. This study implements low‐cost 3D printers to fabricate relatively large needle arrays, followed by repeatable shrink‐molding of hydrogels to form high‐resolution molds for solid and hollow MNAs with controllable sizes. The developed strategy further enables modulating surface topography of MNAs to tailor their surface area and instantaneous wettability for controllable drug delivery and body fluid sampling. Hybrid gelatin methacryloyl (GelMA)/polyethylene glycol diacrylate (PEGDA) MNAs are fabricated using the developed strategy that can easily penetrate the skin and enable multimodal drug delivery. The proposed method holds promise for affordable, controllable, and scalable fabrication of MNAs by researchers and clinicians for controlled spatiotemporal administration of therapeutics and sample collection.