Going below and beyond the surface: Microneedle structure, materials, drugs, fabrication, and applications for wound healing and tissue regeneration.

Microneedle, as a novel drug delivery system, has attracted widespread attention due to its non-invasiveness, painless and simple administration, controllable drug delivery, and diverse cargo loading capacity. Although microneedles are initially designed to penetrate stratum corneum of skin for transdermal drug delivery, they, recently, have been used to promote wound healing and regeneration of diverse tissues and organs and the results are promising. Despite there are reviews about microneedles, few of them focus on wound healing and tissue regeneration. Here, we review the recent advances of microneedles in this field. We first give an overview of microneedle system in terms of its potential cargos (e.g., small molecules, macromolecules, nucleic acids, nanoparticles, extracellular vesicle, cells), structural designs (e.g., multidrug structures, adhesive structures), material selection, and drug release mechanisms. Then we briefly summarize different microneedle fabrication methods, including their advantages and limitations. We finally summarize the recent progress of microneedle-assisted wound healing and tissue regeneration (e.g., skin, cardiac, bone, tendon, ocular, vascular, oral, hair, spinal cord, and uterine tissues). We expect that our article would serve as a guideline for readers to design their microneedle systems according to different applications, including material selection, drug selection, and structure design, for achieving better healing and regeneration efficacy.

Biomimicking design of artificial periosteum for promoting bone healing.

Background: Periosteum is a vascularized tissue membrane covering the bone surface and plays a decisive role in bone reconstruction process after fracture. Various artificial periosteum has been developed to assist the allografts or bionic bone scaffolds in accelerating bone healing. Recently, the biomimicking design of artificial periosteum has attracted increasing attention due to the recapitulation of the natural extracellular microenvironment of the periosteum and has presented unique capacity to modulate the cell fates and ultimately enhance the bone formation and improve neovascularization. Methods: A systematic literature search is performed and relevant findings in biomimicking design of artificial periosteum have been reviewed and cited. Results: We give a systematical overview of current development of biomimicking design of artificial periosteum. We first summarize the universal strategies for designing biomimicking artificial periosteum including biochemical biomimicry and biophysical biomimicry aspects. We then discuss three types of novel versatile biomimicking artificial periosteum including physical-chemical combined artificial periosteum, heterogeneous structured biomimicking periosteum, and healing phase-targeting biomimicking periosteum. Finally, we comment on the potential implications and prospects in the future design of biomimicking artificial periosteum. Conclusion: This review summarizes the preparation strategies of biomimicking artificial periosteum in recent years with a discussion of material selection, animal model adoption, biophysical and biochemical cues to regulate the cell fates as well as three types of latest developed versatile biomimicking artificial periosteum. In future, integration of innervation, osteochondral regeneration, and osteoimmunomodulation, should be taken into consideration when fabricating multifunctional artificial periosteum.The Translational Potential of this Article: This study provides a holistic view on the design strategy and the therapeutic potential of biomimicking artificial periosteum to promote bone healing. It is hoped to open a new avenue of artificial periosteum design with biomimicking considerations and reposition of the current strategy for accelerated bone healing.

Shedding light on 3D printing: Printing photo-crosslinkable constructs for tissue engineering.

3D printing has emerged as a pivotal fabrication technique for preparing scaffolds for engineering tissues and tissue models. Among different 3D printing platforms, photo-crosslinking-based 3D printing techniques like digital light processing and stereolithography have become most popular as they enable the construction of complex architecture with improved spatial resolution, reliable pattern fidelity, and high printing speed. In addition, by selecting appropriate ink combinations or modulating the photo-crosslinking printing parameters (e.g., the types or concentrations of photoinitiators and crosslinkers, light exposure time or intensity, as well as the 3D printing techniques used), the structures and properties (e.g., swelling and mechanical properties) of the resultant printed scaffolds can be finely tailored to meet the practical application requirements. Here, recent advances on the promising development of photo-crosslinkable materials for 3D printing with a focus on their biomedical applications for repairing damaged organs and developing in vitro tissue models are reviewed. Firstly, an overview of commonly used photo-crosslinkable materials, as well as insights on how the printing outcomes of these materials can be improved are provided. Then, the diverse regulation strategies of the photo-polymerization process and the 3D printing parameters to improve the performances of the printed structures are summarized. The existing challenges and future directions are finally discussed from the technical and application perspectives of photo-crosslinking-based 3D printing.

Fabrication of Glass Diaphragm Based Fiber-Optic Microphone for Sensitive Detection of Airborne and Waterborne Sounds.

A glass-diaphragm microphone was developed based on fiber-optic Fabry-Perot (FP) interferometry. The glass diaphragm was shaped into a wheel-like structure on a 150-µm-thick glass sheet by laser cutting, which consists of a glass disc connected to an outer glass ring by four identical glass beams. Such a structural diaphragm offers the microphone an open air chamber that reduces air damping and increases sensitivity and results in a cardioid direction pattern for the microphone response. The prepared microphone operates at 1550 nm wavelength, showing high stability in a range of temperature from 10 to 40 °C. The microphone has a resonance peak at 1152 Hz with a quality factor of 21, and its 3-dB cut-off frequency is 32 Hz. At normal incidence of 500 Hz sound, the pressure sensitivity of the microphone is 755 mV/Pa and the corresponding minimum detectable pressure is 251 µPa/Hz1/2. In addition to the above characteristics of the microphone in air, a preliminary investigation reveals that the microphone can also work stably under water for a long time due to the combination of the open-chamber and fiber-optic structures, and it has a large signal-to-noise ratio in response to waterborne sounds. The microphone prepared in this work is simple, inexpensive, and electromagnetically robust, showing great potential for low-frequency acoustic detection in air and under water.

Assessing and managing design storm variability and projection uncertainty in a changing coastal environment.

Coastal urban infrastructure and water management programs are vulnerable to the impacts of long-term hydroclimatic changes and to the flooding and physical destruction of disruptive hurricanes and storm surge. Water resilience or, inversely, vulnerability depends on design specifications of the storm and inundation, against which water infrastructure and environmental assets are planned and operated. These design attributes are commonly derived from statistical modeling of historical measurements. Here we argue for the need to carefully examine the approach and associated design vulnerability in coastal areas because of the future hydroclimatic changes and large variability at local coastal watersheds. This study first shows significant spatiotemporal variations of design storm in the Chesapeake Bay of the eastern U.S. Atlantic coast, where the low-frequency high-intensity precipitations vary differently to the tropical cyclones and local orographic effects. Average and gust wind speed exhibited much greater spatial but far less temporal variability than the precipitation. It is noteworthy that these local variabilities are not fully described by the regional gridded precipitation used in CMIP5 climate downscaling and by NOAA's regional design guide Atlas-14. Up to 46.4% error in the gridded precipitation for the calibration period 1950-1999 is further exacerbated in the future design values by the ensemble of 132 CMIP5 projections. The total model projection error (δM) up to -61.8% primarily comes from the precipitation regionalization (δ1), climate downscaling (δ2), and a fraction from empirical data modeling (δE). Thus, a post-bias correction technique is necessary. The bias-corrected design wind speed for 10-yr to 30-yr storms has small changes <20% by the year 2100, but contains large spatial variations even for stations of close proximity. Bias-corrected design precipitations are characteristic of large spatial variability and a notable increase of 2-5 year precipitation in the future along western shores of the Lower and Middle Chesapeake Bay. All these accounts point to the potential vulnerability of water infrastructure and water program in coastal areas, when the hydrological design basis using regional values fails to account for significant spatiotemporal precipitation variations in local coastal watersheds.