Spatially engineering tri-layer nanofiber dressings featuring asymmetric wettability for wound healing

Inspired by the skin structure,an asymmetric wettability tri-layer nanofiber membrane(TNM)consisting of hydrophilic inner layer loaded with lidocaine hydrochloride(LID),hydrophobic middle layer with ciprofloxacin(CIP)and hydrophobic outer layer has been created.The hydrophobic outer layer endows the TNM with waterproof function and anti-adhesion from contaminants.The hydrophobic middle layer with CIP preserves long-term inhibition of bacteria growth and the hydrophilic inner layer with LID possesses optimal waterabsorbing capacity and air permeability.The TNM dramatically elevates the water contact angles from 10°(inner layer)to 120(outer layer),indicating an asymmetric wettability,which could directionally transport wound exudate within the materials and meanwhile maintain a comfortable and moist environment to promote wound healing.Furthermore,the sequential release of LID and CIP could relieve pain rapidly and achieve antibacterial effect in the long run,respectively.In addition,the TNM shows superior biocompatibility towards L929 cells.The in vivo results show the TNM could prevent infection,accelerate epithelial regeneration and significantly accelerate wound healing.This study indicates the developed TNM with asymmetrical wettability and synergetic drug release shows great potential as a wound dressing in clinical application.

Machine learning-guided accelerated discovery of structure-property correlations in lean magnesium alloys for biomedical applications

Magnesium alloys are emerging as promising alternatives to traditional orthopedic implant materials thanks to their biodegradability,biocompatibility,and impressive mechanical characteristics.However,their rapid in-vivo degradation presents challenges,notably in upholding mechanical integrity over time.This study investigates the impact of high-temperature thermal processing on the mechanical and degradation attributes of a lean Mg-Zn-Ca-Mn alloy,ZX10.Utilizing rapid,cost-efficient characterization methods like X-ray diffraction and optical microscopy,we swiftly examine microstructural changes post-thermal treatment.Employing Pearson correlation coefficient analysis,we unveil the relationship between microstructural properties and critical targets(properties):hardness and corrosion resistance.Additionally,leveraging the least absolute shrinkage and selection operator(LASSO),we pinpoint the dominant microstructural factors among closely correlated variables.Our findings underscore the significant role of grain size refinement in strengthening and the predominance of the ternary Ca_(2)Mg_(6)Zn_(3)phase in corrosion behavior.This suggests that achieving an optimal blend of strength and corrosion resistance is attainable through fine grains and reduced concentration of ternary phases.This thorough investigation furnishes valuable insights into the intricate interplay of processing,structure,and properties in magnesium alloys,thereby advancing the development of superior biodegradable implant materials.

Multilevel analysis of the central-peripheral-target organ pathway:contributing to recovery after peripheral nerve injury

Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.

Development and Characterization of Calcium Based Biocomposites Using Waste Material (Calcite Stones) for Biomedical Applications

Calcium-based biocomposite materials have a pivotal role in the biomedical field with their diverse properties and applications in combating challenging medical problems. The study states the development and characterization of Calcium-based biocomposites: Hydroxyapatite (HAP), and PVA-Gelatin-HAP films. For the preparation of Calcium-based biocomposites, an unconventional source, the waste material calcite stone, was used as calcium raw material, and by the process of calcination, calcium oxide was synthesized. From calcium oxide, HAP was prepared by chemical precipitation method, which was later added in different proportions to PVA-Gelatin solution and finally dried to form biocomposite films. Then the different properties of PVA/Gelatin/HAP composite, for instance, chemical, mechanical, thermal, and swelling properties due to the incorporation of various proportions of HAP in PVA-Gelatin solution, were investigated. The characterization of the HAP was conducted by X-ray Diffraction Analysis, and the characterization of HAP-PVA-Gelatin composites was done by Fourier Transform Infrared Spectroscopy, Thermomechanical Analysis, Tensile test, Thermogravimetric Differential Thermal Analysis, and Swelling Test. The produced biocomposite films might have applications in orthopedic implants, drug delivery, bone tissue engineering, and wound healing.

Bioinspired Ultrasensitive Flexible Strain Sensors for Real‑Time Wireless Detection of Liquid Leakage

Liquid leakage of pipeline networks not only results in considerableresource wastage but also leads to environmental pollution and ecological imbalance.In response to this global issue, a bioinspired superhydrophobic thermoplastic polyurethane/carbon nanotubes/graphene nanosheets flexible strain sensor (TCGS) hasbeen developed using a combination of micro-extrusion compression molding andsurface modification for real-time wireless detection of liquid leakage. The TCGSutilizes the synergistic effects of Archimedean spiral crack arrays and micropores,which are inspired by the remarkable sensory capabilities of scorpions. This designachieves a sensitivity of 218.13 at a strain of 2%, which is an increase of 4300%. Additionally, it demonstrates exceptional durability bywithstanding over 5000 usage cycles. The robust superhydrophobicity of the TCGS significantly enhances sensitivity and stability indetecting small-scale liquid leakage, enabling precise monitoring of liquid leakage across a wide range of sizes, velocities, and compositionswhile issuing prompt alerts. This provides critical early warnings for both industrial pipelines and potential liquid leakage scenariosin everyday life. The development and utilization of bioinspired ultrasensitive flexible strain sensors offer an innovative and effectivesolution for the early wireless detection of liquid leakage.

Activation of adult endogenous neurogenesis by a hyaluronic acid collagen gel containing basic fibroblast growth factor promotes remodeling and functional recovery of the injured cerebral cortex

The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.

Medical colleges summary of biomedical engineering profession<br>—Luzhou Medical College in the perspective of biomedical engineering profession<br>

This paper expounds professional characteristics of biomedical engineering in our school, and analyses some problems lying in it, emphatically discusses advantages and the problems combining biomedical engineering with the medical courses in order to offer targeted solutions. It summarizes the results and problems so as to provide reference value to a new major.

Biomimetic delivery of signals for bone tissue engineering

Bone tissue engineering is an exciting approach to directly repair bone defects or engineer bone tissue for transplantation.Biomaterials play a pivotal role in providing a template and extracellular environment to support regenerative cells and promote tissue regeneration. A variety of signaling cues have been identified to regulate cellular activity, tissue development, and the healing process. Numerous studies and trials have shown the promise of tissue engineering, but successful translations of bone tissue engineering research into clinical applications have been limited, due in part to a lack of optimal delivery systems for these signals. Biomedical engineers are therefore highly motivated to develop biomimetic drug delivery systems, which benefit from mimicking signaling molecule release or presentation by the native extracellular matrix during development or the natural healing process. Engineered biomimetic drug delivery systems aim to provide control over the location, timing, and release kinetics of the signal molecules according to the drug's physiochemical properties and specific biological mechanisms. This article reviews biomimetic strategies in signaling delivery for bone tissue engineering, with a focus on delivery systems rather than specific molecules. Both fundamental considerations and specific design strategies are discussed with examples of recent research progress, demonstrating the significance and potential of biomimetic delivery systems for bone tissue engineering.

Engineering mesenchymal stromal/stem cell-derived extracellular vesicles with improved targeting and therapeutic efficiency for the treatment of central nervous system disorders

Treatment for central nervous system(CNS)disorders is known to be limited by the low regenerative potential of neurons,and thus neurodegenerative insults became known as nearly irreversible ailments.Functional recovery for acquired CNS disorders,such as spinal cord injury(SCI),traumatic brain injury,ischemic stroke,Alzheimer’s disease,Parkinson’s disease,multiple sclerosis(MS),and for congenital CNS abnormalities,such as spina bifida,is not spontaneous and effective treatments are limited to non-existent.Research in the past decades has proven the regenerative potential of stem cells,especially that of mesenchymal stromal/stem cells(MSCs)from various origins,such as bone marrow,placenta,and adipose tissue.

BME 2.0: Engineering the Future of Medicine

If the 20th century was the age of mapping and controlling the external world,the 21st century is the biomedical age of mapping and controlling the biological internal world.The biomedical age is bringing new technological breakthroughs for sensing and controlling human biomolecules,cells,tissues,and organs,which underpin new frontiers in the biomedical discovery,data,biomanufacturing,and translational sciences.This article reviews what we believe will be the next wave of biomedical engineering(BME)education in support of the biomedical age,what we have termed BME 2.0.BME 2.0 was announced on October 122017 at BMES 49(https://www.bme.jhu.edu/news-events/news/miller-opens-2017-bmes-annual-meeting-with-vision-for-new-bme-era/).We present several principles upon which we believe the BME 2.0 curriculum should be constructed,and from these principles,we describe what view as the foundations that form the next generations of curricula in support of the BME enterprise.The core principles of BME 2.0 education are(a)educate students bilingually,from day 1,in the languages of modern molecular biology and the analytical modeling of complex biological systems;(b)prepare every student to be a biomedical data scientist;(c)build a unique BME community for discovery and innovation via a vertically integrated and convergent learning environment spanning the university and hospital systems;(d)champion an educational culture of inclusive excellence;and(e)codify in the curriculum ongoing discoveries at the frontiers of the discipline,thus ensuring BME 2.0 as a launchpad for training the future leaders of the biotechnology marketplaces.We envision that the BME 2.0 education is the path for providing every student with the training to lead in this new era of engineering the future of medicine in the 21st century.

3D biofabrication for tubular tissue engineering

The therapeutic replacement of diseased tubular tissue is hindered by the availability and suitability of current donor, autologous and synthetically derived protheses. Artificially created, tissue engineered, constructs have the potential to alleviate these concerns with reduced autoimmune response, high anatomical accuracy, long-term patency and growth potential. The advent of 3D bioprinting technology has further supplemented the technological toolbox, opening up new biofabrication research opportunities and expanding the therapeutic potential of the field. In this review, we highlight the challenges facing those seeking to create artificial tubular tissue with its associated complex macro- and microscopic architecture. Current biofabrication approaches, including 3D printing techniques, are reviewed and future directions suggested.

The secondary injury cascade after spinal cord injury:an analysis of local cytokine/chemokine regulation

After spinal cord injury,there is an extensive infiltration of immune cells,which exacerbates the injury and leads to further neural degeneration.Therefore,a major aim of current research involves targeting the immune response as a treatment for spinal cord injury.Although much research has been performed analyzing the complex inflammatory process following spinal cord injury,there remain major discrepancies within previous literature regarding the timeline of local cytokine regulation.The objectives of this study were to establish an overview of the timeline of cytokine regulation for 2 weeks after spinal cord injury,identify sexual dimorphisms in terms of cytokine levels,and determine local cytokines that significantly change based on the severity of spinal cord injury.Rats were inflicted with either a mild contusion,moderate contusion,severe contusion,or complete transection,7 mm of spinal cord centered on the injury was harvested at varying times post-injury,and tissue homogenates were analyzed with a Cytokine/Chemokine 27-Plex assay.Results demonstrated pro-inflammatory cytokines including tumor necrosis factorα,interleukin-1β,and interleukin-6 were all upregulated after spinal cord injury,but returned to uninjured levels within approximately 24 hours post-injury,while chemokines including monocyte chemoattractant protein-1 remained upregulated for days post-injury.In contrast,several anti-inflammatory cytokines and growth factors including interleukin-10 and vascular endothelial growth factor were downregulated by 7 days post-injury.After spinal cord injury,tissue inhibitor of metalloproteinase-1,which specifically affects astrocytes involved in glial scar development,increased more than all other cytokines tested,reaching 26.9-fold higher than uninjured rats.After a mild injury,11 cytokines demonstrated sexual dimorphisms;however,after a severe contusion only leptin levels were different between female and male rats.In conclusion,pro-inflammatory cytokines initiate the inflammatory process and return to baseline within hours post-injury,chemokines continue to recruit immune cells for days post-injury,while anti-inflammatory cytokines are downregulated by a week post-injury,and sexual dimorphisms observed after mild injury subsided with more severe injuries.Results from this work define critical chemokines that influence immune cell infiltration and important cytokines involved in glial scar development after spinal cord injury,which are essential for researchers developing treatments targeting secondary damage after spinal cord injury.

Activation of endogenous neurogenesis and angiogenesis by basic fibroblast growth factor-chitosan gel in an adult rat model of ischemic stroke

Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.

Local dose-dense chemotherapy for triple-negative breast cancer via minimally invasive implantation of 3D printed devices

Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer(TNBC),a highly aggressive disease with a poor prognosis.This treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals,allowing for promising clinical outcomes with intensive treatment.However,the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance,limiting therapeutic efficacy and clinical benefit.Here,we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with timeprogrammed pulsatile release profiles.The implantable device can control the time between drug releases based on its internal microstructure design,which can be used to control dose density.The device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a trocar.Dose density variation of local chemotherapy using programmable release enhances anti-cancer effects in vitro and in vivo.Under the same dose density conditions,device-based chemotherapy shows a higher anticancer effect and less toxic response than intratumoral injection.We demonstrate local chemotherapy utilizing the implantable device that simulates the drug dose,number of releases,and treatment duration of the dose-dense AC(doxorubicin and cyclophosphamide)regimen preferred for TNBC treatment.Dose density modulation inhibits tumor growth,metastasis,and the expression of drug resistance-related proteins,including p-glycoprotein and breast cancer resistance protein.To the best of our knowledge,local dose-dense chemotherapy has not been reported,and our strategy can be expected to be utilized as a novel alternative to conventional therapies and improve anti-cancer efficiency.

Soft,body conformable electronics for thermoregulation enabled by kirigami

The application of thermoelectric devices(TEDs)for personalized thermoregulation is attractive for saving energy while balancing the quality of life.TEDs that directly attach to human skin remarkably minimized the energy wasted for cooling the entire environment.However,facing the extreme dynamic geometry change and strain of human skin,conventional TEDs cannot align with the contour of our bodies for the best thermoregulation effect.Hence,we designed a kirigami-based wearable TED with excellent water vapor permeability,flexibility,and conformability.Numerical analysis and experimental results reveal that our product can withstand various types of large mechanical deformation without circuit rupture.The stated outcome and proposed facile approach not only reinforce the development of wearable TEDs but also offer an innovative opportunity for different electronics that require high conformability.

Brain regulates weight bearing bone through PGE2 skeletal interoception: implication of ankle osteoarthritis and pain

Bone is a mechanosensitive tissue and undergoes constant remodeling to adapt to the mechanical loading environment.However,it is unclear whether the signals of bone cells in response to mechanical stress are processed and interpreted in the brain.In this study,we found that the hypothalamus of the brain regulates bone remodeling and structure by perceiving bone prostaglandin E2(PGE2)concentration in response to mechanical loading.Bone PGE2 levels are in proportion to their weight bearing.When weight bearing changes in the tail-suspension mice,the PGE2 concentrations in bones change in line with their weight bearing changes.Deletion of cyclooxygenase-2(COX2)in the osteoblast lineage cells or knockout of receptor 4(EP4)in sensory nerve blunts bone formation in response to mechanical loading.Moreover,knockout of TrkA in sensory nerve also significantly reduces mechanical load-induced bone formation.Moreover,mechanical loading induces cAMP-response element binding protein(CREB)phosphorylation in the hypothalamic arcuate nucleus(ARC)to inhibit sympathetic tyrosine hydroxylase(TH)expression in the paraventricular nucleus(PVN)for osteogenesis.Finally,we show that elevated PGE2 is associated with ankle osteoarthritis(AOA)and pain.Together,our data demonstrate that in response to mechanical loading,skeletal interoception occurs in the form of hypothalamic processing of PGE2-driven peripheral signaling to maintain physiologic bone homeostasis,while chronically elevated PGE2 can be sensed as pain during AOA and implication of potential treatment.

Morphological Evaluation of PLA/Soybean Oil Epoxidized Acrylate Three-Dimensional Scaffold in Bone Tissue Engineering

Tissue engineering’s main goal is to regenerate or replace tissues or organs that have been destroyed by disease,injury,or congenital disabilities.Tissue engineering now uses artificial supporting structures called scaffolds to restore damaged tissues and organs.These are utilized to attach the right cells and then grow them.Rapid prototyping appears to be the most promising technology due to its high level of precision and control.Bone tissue replacement“scaffolding”is a common theme discussed in this article.The fused deposition technique was used to construct our scaffold,and a polymer called polylactic acids and soybean oil resin were used to construct our samples.The samples were then divided into two groups;the first group was left without immersion in the simulated body fluid and served as a control for comparison.The second group was immersed in the simulated body fluid.The results of the Field Emission Scanning Electron Microscope(FESEM),Energy Dispersive X-ray Spectroscopy(EDX)and X-ray diffraction(XRD)were utilized to interpret the surface attachment to ions,elements,and compounds,giving us a new perspective on scaffold architecture.In this study,an innovative method has been used to print therapeutic scaffold that combines fused deposition three-dimensional printing with ultraviolet curing to create a high-quality biodegradable polymeric scaffold.Finally,the results demonstrate that adding soybean oil resin to the PLA increased ion attachment to the surface while also attracting tricalcium phosphate formation on the surface of the scaffold,which is highly promising in bone tissue replacement.In conclusion,the soybean oil resin,which is new in the field of bone tissue engineering,shows magnificent characteristics and is a good replacement biopolymer that replaces many ceramic and polymeric materials used in this field that have poor morphological characteristics.

Mechanism Interpretation of the Biological Brain Cooling and Its Inspiration on Bionic Engineering

The brain is one of the most important organs in a biological body which can only work in a relatively stable temperature range. However, many environmental factors in biosphere would cause cerebral temperature fluctuations. To sustain and regulate the brain temperature, many mechanisms of biological brain cooling have been evolved, including Selective Brain Cooling （SBC）, cooling through surface water evaporation, respiration, behavior response and using special anatomical ap- pendages. This article is dedicated to present a summarization and systematic interpretation on brain cooling strategies devel- oped in animals by classifying and comparatively analyzing each typical biological brain cooling mechanism from the per- spective of bio-heat transfer. Meanwhile, inspirations from such cooling in nature were proposed for developing advanced bionic engineering technologies especially with two focuses on therapeutic hypothermia and computer chip cooling areas. It is expected that many innovations can be achieved along this way to find out new cooling methodologies for a wide variety of industrial applications which will be highly efficient, energy saving, flexible or even intelligent.

Robust adaptive leaderless consensus of unknown non-minimum phase linear multi-agent systems subject to disturbances and/or unmodeled dynamics

This article investigates the problem of robust adaptive leaderless consensus for heterogeneous uncertain nonminimumphase linear multi-agent systems over directed communication graphs. Each agent is assumed tobe of unknown nominal dynamics and also subject to external disturbances and/or unmodeled dynamics. Anovel distributed robust adaptive control strategy is proposed. It is shown that the robust adaptive leaderlessconsensus problem is solved with the proposed control strategy under some sufficient conditions. Two examplesare provided to demonstrate the efficacy of the proposed control strategy.

Estradiol increases cortical and trabecular bone accrual and bone strength in an adolescent male-to-female mouse model of gender-affirming hormone therapy

The effects of gender-affirming hormone therapy on the skeletal integrity and fracture risk in transitioning adolescent trans girls are unknown.To address this knowledge gap,we developed a mouse model to simulate male-to-female transition in human adolescents in whom puberty is first arrested by using gonadotrophin-releasing hormone analogs with subsequent estradiol treatment.Puberty was suppressed by orchidectomy in male mice at 5 weeks of age.At 3 weeks post-surgery,male-to-female mice were treated with a high dose of estradiol(~0.85 mg)by intraperitoneal silastic implantation for 12 weeks.Controls included intact and orchidectomized males at 3 weeks post-surgery,vehicle-treated intact males,intact females and orchidectomized males at 12 weeks post-treatment.Compared to male controls,orchidectomized males exhibited decreased peak bone mass accrual and a decreased maximal force the bone could withstand prior to fracture.Estradiol treatment in orchidectomized male-to-female mice compared to mice in all control groups was associated with an increased cortical thickness in the mid-diaphysis,while the periosteal circumference increased to a level that was intermediate between intact male and female controls,resulting in increased maximal force and stiffness.In trabecular bone,estradiol treatment increased newly formed trabeculae arising from the growth plate as well as mineralizing surface/bone surface and bone formation rate,consistent with the anabolic action of estradiol on osteoblast proliferation.These data support the concept that skeletal integrity can be preserved and that long-term fractures may be prevented in trans girls treated with GnRHa and a sufficiently high dose of GAHT.Further study is needed to identify an optimal dose of estradiol that protects the bone without adverse side effects.