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Electrospun nanofibers show great potential in biomedical applications. This mini review article traces the recent advances in electrospun nanofibers for wound management via various approaches. Initially, we provide a short note on the four phases of wound healing, including hemostasis, inflammation, proliferation, and remodeling. Then, we state how the nanofiber dressings can stop bleeding and reduce the pain. Following that, we discuss the delivery of therapeutics and cells using different types of nanofibers for enhancing cell migration, angiogenesis, and re-epithelialization, resulting in the promotion of wound healing. Finally, we present the conclusions and future perspectives regarding the use of electrospun nanofibers for wound management.

Accurate and rapid point-of-care tissue and microbiome sampling is critical for early detection of cancers and infectious diseases and often result in effective early intervention and prevention of disease spread. In particular, the low prevalence of Barrett's and gastric premalignancy in the Western world makes population-based endoscopic screening unfeasible and cost-ineffective. Herein, we report a method that may be useful for prescreening the general population in a minimally invasive way using a swallowable, re-expandable, ultra-absorbable, and retrievable nanofiber cuboid and sphere produced by electrospinning, gas-foaming, coating, and crosslinking. The water absorption capacity of the cuboid- and sphere-shaped nanofiber objects is shown ∼6000% and ∼2000% of their dry mass. In contrast, unexpanded semicircular and square nanofiber membranes showed500% of their dry mass. Moreover, the swallowable sphere and cuboid were able to collect and release more bacteria, viruses, and cells/tissues from solutions as compared with unexpanded scaffolds. In addition to that, an expanded sphere shows higher cell collection capacity from the esophagus inner wall as compared with the unexpanded nanofiber membrane. Taken together, the nanofiber capsules developed in this study could provide a minimally invasive method of collecting biological samples from the duodenal, gastric, esophagus, and oropharyngeal sites, potentially leading to timely and accurate diagnosis of many diseases. STATEMENT OF SIGNIFICANCE: Recently, minimally invasive technologies have gained much attention in tissue engineering and disease diagnosis. In this study, we engineered a swallowable and retrievable electrospun nanofiber capsule serving as collection device to collect specimens from internal organs in a minimally invasive manner. The sample collection device could be an alternative endoscopy to collect the samples from internal organs like jejunum, stomach, esophagus, and oropharynx without any sedation. The newly engineered nanofiber capsule could be used to collect, bacteria, virus, fluids, and cells from the abovementioned internal organs. In addition, the biocompatible and biodegradable nanofiber capsule on a string could exhibit a great sample collection capacity for the primary screening of Barret Esophagus, acid reflux, SARS-COVID-19, Helicobacter pylori, and gastric cancer.

Due to their biomimetic properties, electrospun nanofibers have shown great potential in many biomedical fields. However, traditionally‐produced nanofibers are typically two‐dimensional (2D) membranes limiting their applications. Herein, we report a large‐scale synthesis of compressible and re‐expandable three‐dimensional (3D) nanofiber matrices for potential biomedical applications. The reproducible mass production of such matrices is achieved using a multiple‐emitter electrospinning machine with a controlled environment (e.g., temperature, humidity, and air flow rate) followed by an innovative gas‐foaming expansion. The modified 20‐emitter circular array with 3D‐printed needle caps is capable of maintaining stable Taylor cones under extremely high flow rates. The introduction of such an emitter array allows for the production rate of 3D nanofiber matrices to increase by over 800 times while retaining the desired morphological, mechanical, and absorptive properties when compared to ones generated by a single‐nozzle electrospinning setup. Taken together, a feasible, optimized method has been demonstrated for scaling up production of shape‐recoverable, expansile nanofiber matrices, representing a step towards translating such materials into preclinical, large animal testing, clinical trials, and eventually clinical applications.

Biofilms in chronic wounds, including diabetic foot ulcers, pressure ulcers, and venous leg ulcers, pose a major challenge to wound management. Herein, we report a Janus-type antimicrobial dressing for eradication of biofilms in chronic wounds. The dressing consists of electrospun nanofiber membranes coupled with dissolvable microneedle arrays to enable effective delivery of a database-designed antimicrobial peptide to both inside and outside biofilms. This antimicrobial dressing exhibited high efficacy against a broad spectrum of resistant pathogens in vitro. Importantly, such a dressing was able to eradicate methicillin-resistant Staphylococcus aureus (MRSA) biofilms in both an ex vivo human skin wound infection model and a type II diabetic mouse wound infection model after daily treatment without applying surgical debridement. Most importantly, the dressing can also completely remove the Pseudomonas aeruginosa and MRSA, dual-species biofilm in an ex vivo human skin infection model. In addition, our computational simulations also suggested that microneedles were more effective in the delivery of peptides to the biofilms than free drugs. Our results indicate that the Janus-type antimicrobial dressings may provide an effective treatment and management of chronic wound polymicrobial infections.

The management of diabetic wounds remains a major therapeutic challenge in clinics. Herein, we report a personalized treatment using 3D scaffolds consisting of radially or vertically aligned nanofibers in combination with bone marrow mesenchymal stem cells (BMSCs). The 3D scaffolds have customizable sizes, depths, and shapes, enabling them to fit a variety of type 2 diabetic wounds. In addition, the 3D scaffolds are shape-recoverable in atmosphere and water following compression. The BMSCs-laden 3D scaffolds are capable of enhancing the formation of granulation tissue, promoting angiogenesis, and facilitating collagen deposition. Further, such scaffolds inhibit the formation of M1-type macrophages and the expression of pro-inflammatory cytokines IL-6 and TNF-α and promote the formation of M2-type macrophages and the expression of anti-inflammatory cytokines IL-4 and IL-10. Taken together, BMSCs-laden, 3D nanofiber scaffolds with controlled structure and alignment hold great promise for the treatment of diabetic wounds. Statement of Significance In this study, we developed 3D radially and vertically aligned nanofiber scaffolds to transplant bone marrow mesenchymal stem cells (BMSCs). We personalized 3D scaffolds that could completely match the size, depth, and shape of diabetic wounds. Moreover, both the radially and vertically aligned nanofiber scaffolds could completely recover their shape and maintain structural integrity after repeated loads with compressive stresses. Furthermore, the BMSCs-laden 3D scaffolds are able to promote granulation tissue formation, angiogenesis, and collagen deposition, and switch the immune responses to the pro-regenerative direction. These 3D scaffolds consisting of radially or vertically aligned nanofibers in combination with BMSCs offer a robust, customizable platform potentially for a significant improvement of managing diabetic wounds.

Over the past two decades electrospinning has been emerged as an enabling nanotechnology to produce nanofiber materials for various biomedical applications. In particular, therapeutic/cell loaded nanofiber scaffolds have been widely examined in drug delivery, wound healing, and tissue repair and regeneration. However, due to the insufficient porosity, small pore size, noninjectability, and inaccurate spatial control in nanofibers of scaffolds, many efforts have been devoted to exploring the new forms of nanofiber materials including expanded nanofiber scaffolds, nanofiber aerogels, short nanofibers, and nanofiber microspheres. This short review discusses preparation and potential biomedical applications of new forms of nanofiber materials, and future directions.

Electrostatic flocking immobilizes electrical charges to the surface of microfibers from a high voltage-connected electrode and utilizes Coulombic forces to propel microfibers toward an adhesive-coated substrate, leaving a forest of aligned fibers. This traditional textile engineering technique has been used to modify surfaces or to create standalone anisotropic structures. Notably, a small body of evidence validating the use of electrostatic flocking for biomedical applications has emerged over the past several years. Noting the growing interest in utilizing electrostatic flocking in biomedical research, we aim to provide an overview of electrostatic flocking, including the principle, setups, and general and biomedical considerations, and propose a variety of biomedical applications. We begin with an introduction to the development and general applications of electrostatic flocking. Additionally, we introduce and review some of the flocking physics and mathematical considerations. We then discuss how to select, synthesize, and tune the main components (flocking fibers, adhesives, substrates) of electrostatic flocking for biomedical applications. After reviewing the considerations necessary for applying flocking toward biomedical research, we introduce a variety of proposed use cases including bone and skin tissue engineering, wound healing and wound management, and specimen swabbing. Finally, we presented the industrial comments followed by conclusions and future directions. We hope this review article inspires a broad audience of biomedical, material, and physics researchers to apply electrostatic flocking technology to solve a variety of biomedical and materials science problems.

Drawing inspiration for biomaterials from biological systems has led to many biomedical innovations. One notable bioinspired device, Velcro, consists of two substrates with interlocking ability. Generating reversibly interlocking biomaterials is an area of investigation, as such devices could allow for modular tissue engineering, reversibly interlocking biomaterial interfaces, or friction-based coupling devices. Here, we report a biaxially-interlocking interface generated using electrostatic flocking. Two electrostatically flocked substrates are mechanically and reversibly interlocked with the ability to resist shearing and compression forces. An initial high-throughput screen of polyamide flock fibers with varying diameters and fiber lengths was conducted to elucidate the roles of different fiber parameters on scaffold mechanical properties. After determining the most desirable parameters via weight scoring, polylactic acid (PLA) fibers were used to emulate the ideal scaffold for in vitro use. PLA flocked scaffolds were populated with osteoblasts and interlocked. Interlocked flocked scaffolds improved cell survivorship under mechanical compression and sustained cell viability and proliferation. Additionally, the compression and shearing resistance of cell-seeded interlocking interfaces increased with increasing extracellular matrix deposition. The introduction of extracellular matrix-reinforced interlocking interfaces may serve as binders for modular tissue engineering, act as scaffolds for engineering tissue interfaces, or enable friction-based couplers for biomedical applications. This article is protected by copyright. All rights reserved.

Electrostatic flocking is a textile technology that employs a Coulombic driving force to launch short fibers from a charging source towards an adhesive-covered substrate, resulting in a dense array of aligned fibers perpendicular to the substrate. However, electrostatic flocking of insulative polymeric fibers remains a challenge due to their insufficient charge accumulation. We report a facile method to flock electrostatically insulative poly(ε-caprolactone) (PCL) microfibers (MFs) and electrospun PCL nanofiber yarns (NFYs) by incorporating NaCl during pre-flock processing. Both MF and NFY were evaluated for flock functionality, mechanical properties, and biological responses. To demonstrate this platform's diverse applications, standalone flocked NFY and MF scaffolds were synthesized and evaluated as scaffold for cell growth. Employing the same methodology, scaffolds made from poly(glycolide-co-l-lactide) (PGLA) (90:10) MFs were evaluated for their wound healing capacity in a diabetic mouse model. Further, a flock-reinforced polydimethylsiloxane (PDMS) disc was fabricated to create an anisotropic artificial vertebral disc (AVD) replacement potentially used as a treatment for lumbar degenerative disc disease. Overall, a salt-based flocking method is described with MFs and NFYs, with wound healing and AVD repair applications presented., Graphical abstract This work reports electrostatic flocking of salt-treatment microfibers and nanofiber yarns for applications in wound healing and artificial vertebral disc replacement.Image 1, Highlights • NaCl coatings enable sufficient charge accumulation on electrically insulative polymer fibers during electrostatic flocking. • Flocked nanofiber yarns allow further functionalization of flocked scaffolds. • Flocked fiber scaffolds sustain cell proliferation. • Flocked PGLA (90:10) fiber scaffolds promote modest fiber-density dependent wound healing and angiogenesis. • Flock fibers-reinforced elastomeric artificial vertebral discs are mechanically robust.

Biomaterials without incorporating therapeutic agents and living cells effectively repair critical-sized rat cranial bone defects., Biomaterials without exogenous cells or therapeutic agents often fail to achieve rapid endogenous bone regeneration with high quality. Here, we reported a class of three-dimensional (3D) nanofiber scaffolds with hierarchical structure and controlled alignment for effective endogenous cranial bone regeneration. 3D scaffolds consisting of radially aligned nanofibers guided and promoted the migration of bone marrow stem cells from the surrounding region to the center in vitro. These scaffolds showed the highest new bone volume, surface coverage, and mineral density among the tested groups in vivo. The regenerated bone exhibited a radially aligned fashion, closely recapitulating the scaffold’s architecture. The organic phase in regenerated bone showed an aligned, layered, and densely packed structure, while the inorganic mineral phase showed a uniform distribution with smaller pore size and an even distribution of stress upon the simulated compression. We expect that this study will inspire the design of next-generation biomaterials for effective endogenous bone regeneration with desired quality.

Many measures have been taken since late 2019 to combat the coronavirus disease (COVID-19) pandemic. National, state, and local governments employed precautions, including mask mandates, stay-at-home orders, and social distancing policies, to alleviate the burden on healthcare workers and slow the spread of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) virus until an efficacious vaccine was made widely available. By early spring of 2021, three effective and well-tolerated SARS-CoV-2 vaccines emerged and underwent broad distribution. Throughout the course of the COVID-19 vaccination campaign, several key logistical and psychological issues surfaced. Of these, access to vaccines and vaccination hesitancy are cited as two substantial hindrances towards vaccination. Noting the demand for the SARS-CoV-2 vaccine and its highly sensitive storage requirements, accurate dose allocation is critical for vaccinating the population quickly and successfully. Here, we propose the use of social data as a tool to predict vaccination participation by correlating Google searches with state-level daily vaccination. We identified a temporal and regionally-ubiquitous Google search syntax that broadly captures daily vaccination trends. By correlating trends in the search syntax with daily vaccination rates, we were able to quantify the correlation and identify optimal lag periods between Google searches and daily vaccination. This work highlights the importance of analyzing social data as a metric to effectively arrange vaccination roll-outs, identify voluntary vaccination participation, and identify inflection points in vaccination participation. In addition, social data assessments can help direct dose allocation, identify geographic areas that may seek, but lack, access to the vaccines, and actively prepare for fluctuations in vaccination demands.

Background In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a novel virus and initiated a series of events that culminated in the global coronavinis disease 2019 (COVID-19) pandemic. Throughout 2020 and the first half of 2021, massive investigational efforts towards identifying, treating, preventing, and slowing the spread of COVID-19 were carried out. Several predictors for clinical outcomes relating to metabolic health were identified. Aim and methods This study aimed to investigate how public interest in search terms associated with metabolic health has changed throughout and during the course of the COVID-19 pandemic. Google Trends was utilized as a tool to gather and compare public interest data in a variety of search phrases. The relative search values were plotted over time, compared pre-and post-COVID-19, analyzed for correlation, assessed for trend directionality, and checked for trend inclusion. Results The public interest measured by relative search volume in "metabolic health," "exercise," "home exercise,' "health," and "how to improve fitness" significantly increased from pre- to post-COVID-19 pandemic onset while "diet" and "fitness" significantly decreased. The search terms "COVID" and "coronavints" made up more than 95% of screen queries incorporating COVID-19. During the COVID-19 pandemic, "diabetes" and "weight loss" had the most significant increases in search volume. Conclusions Given the changes in public interest observed throughout the course of the COVID-19 pandemic, it is clear that the association between metabolic health and COVID-19 is being successfully disseminated to the public. However, these changes also warrant increased public education surrounding diet and fitness to align public interest with measures proven to improve the clinical outcomes of COVID-19.

Electrostatic flocking, a textile engineering technique, uses Coulombic driving forces to propel conductive microfibers towards an adhesive-coated substrate, leaving a forest of aligned fibers. Though an easy way to induce anisotropy along a surface, this technique is limited to microfibers capable of charge transfer and accumulation from charging surfaces to microfibers. This study reports a novel method, utilizing principles from the percolation theory, to make electrically-insulative polymeric microfibers flockable. A variety of well-mixed conductive materials are added to multiple insulative and biodegradable polymer microfibers during wet spinning, which enables nearly all types of polymer microfibers to accumulate sufficient charges required for flocking. Biphasic, biodegradable scaffolds are fabricated by flocking silver nanoparticle (AgNP)-filled poly(ε-caprolactone) (PCL) microfibers onto substrates made from three-dimensional (3D) printing, electrospinning, and thin-film casting. The incorporation of AgNP into PCL fibers and use of chitosan-based adhesive enables antimicrobial activity against methicillin-resistant Staphylococcus aureus. The fabricated scaffolds demonstrated both favorable in vitro cell response and new tissue formation after subcutaneous implantation in rats as evidenct by new blood vessels and infiltrated cells. This technology opens many doors for using once unflockable polymer microfibers as surface modifiers or standalone structures in many engineering fields.

Following the COVID-19 outbreak, swabs for biological specimen collection were thrust to the forefront of healthcare materials. Swab sample collection and recovery are vital for reducing false negative diagnostic tests, early detection of pathogens, and harvesting DNA from limited biological samples. In this study, we report a new class of nanofiber swabs tipped with hierarchical 3D nanofiber objects produced by expanding electrospun membranes with a solids-of-revolution-inspired gas foaming technique. Nanofiber swabs significantly improve absorption and release of proteins, cells, bacteria, DNA, and viruses from solutions and surfaces. Implementation of nanofiber swabs in SARS-CoV-2 detection reduces the false negative rates at two viral concentrations and identifies SARS-CoV-2 at a 10× lower viral concentration compared to flocked and cotton swabs. The nanofiber swabs show great promise in improving test sensitivity, potentially leading to timely and accurate diagnosis of many diseases.

New methods are described for converting two-dimensional (2D) electrospun nanofiber membranes to three-dimensional (3D) hierarchical assemblies with structural and compositional gradients. Pore size gradients are generated by tuning the expansion of 2D membranes in different layers with incorporation of various amounts of a surfactant during the gas-foaming process. The gradient in fiber organizations is formed by expanding 2D nanofiber membranes composed of multiple regions collected by varying rotating speeds of mandrel. The compositional gradient on 3D assemblies consisting of radially aligned nanofibers is prepared by dripping, diffusion, and crosslinking. Bone mesenchymal stem cells (BMSCs) on the 3D nanofiber assemblies with smaller pore size show significantly higher expression of hypoxia related markers and enhanced chondrogenic differentiation compared to BMSCs cultured on the assemblies with larger pore size. The basic fibroblast growth factor (bFGF) gradient can accelerate fibroblast migration from the surrounding area to the center in an in vitro wound healing model. Taken together, 3D nanofiber assemblies with gradients in pore sizes, fiber organizations, and contents of signaling molecules can be used to engineer tissue constructs for tissue repair and build biomimetic disease models for studying disease biology and screening drugs, in particular, for interface tissue engineering and modeling.

Biofilms in chronic wounds, including diabetic foot ulcers, pressure ulcers, and venous leg ulcers, pose a major challenge to wound management. Herein, we report a Janus-type antimicrobial dressing for eradication of biofilms in chronic wounds. The dressing consists of electrospun nanofiber membranes coupled with dissolvable microneedle arrays to enable effective delivery of a database designed antimicrobial peptide to both inside and outside biofilms. This antimicrobial dressing exhibited high efficacy against a broad spectrum of resistant pathogens in vitro. Importantly, such a dressing was able to eradicate methicillin-resistant Staphylococcus aureus (MRSA) biofilms in both an ex vivo human skin wound infection model and a type II diabetic mouse wound infection model after daily treatment without applying surgical debridement. Most importantly, the dressing can also completely remove the Pseudomonas aeruginosa and MRSA, dual-species biofilm in an ex vivo human skin infection model. In addition, our computational simulations also suggested that microneedles were more effective in the delivery of peptides to the biofilms than free drugs. Our results indicate that the Janus-type antimicrobial dressings may provide an effective treatment and management of chronic wound polymicrobial infections.

Minimally invasive therapies avoiding surgical complexities evoke great interest in developing injectable biomedical devices. Herein, a versatile approach is reported for engineering injectable and biomimetic nanofiber microspheres (NMs) with tunable sizes, predesigned structures, and desired compositions via gas bubble-mediated coaxial electrospraying. The sizes and structures of NMs are controlled by adjusting processing parameters including air flow rate, applied voltage, distance, and spinneret configuration in the coaxial setup. Importantly, unlike the self-assembly method, this technique can be used to fabricate NMs from any material feasible for electrospinning or other nanofiber fabrication techniques. To demonstrate the versatility, open porous NMs are successfully fabricated that consist of various short nanofibers made of poly(e-caprolactone), poly(lactic-co-glycolic acid), gelatin, methacrylated gelatin, bioglass, and magneto-responsive polymer composites. Open porous NMs support human neural progenitor cell growth in 3D with a larger number and more neurites than nonporous NMs. Additionally, highly open porous NMs show faster cell infiltration and host tissue integration than nonporous NMs after subcutaneous injection to rats. Such a novel class of NMs holds great potential for many biomedical applications such as tissue filling, cell and drug delivery, and minimally invasive tissue regeneration.

Alzheimer’s disease (AD) is a neurodegenerative disorder affecting 35 million people worldwide. A common strategy to improve the well-being of AD patients consists on the inhibition of acetylcholinesterase with the concomitant increase of the neurotransmitter acetylcholine at cholinergic synapses. Two series of unreported N-benzylpiperidines 5(a–h) and thiazolopyrimidines 9(a–q) molecules were synthesized and evaluated in vitro for their acetylcholinesterase (AChE) inhibitory activities. Among the newly synthesized compounds, 5h, 9h, 9j, and 9p displayed higher AChE enzyme inhibitory activities than the standard drug, galantamine, with IC50 values of 0.83, 0.98, and 0.73 μM, respectively. Cytotoxicity studies of 5h, 9h, 9j, 9n and 9p on human neuroblastoma cells SH-SY5Y, showed no toxicity up to 40 μM concentration. Molecular docking simulations of the active compounds 5h and 9p disclosed the crucial role of π-π-stacking in their binding interaction to the active site AChE enzyme. The presented compounds have potential as AChE inhibitors and potential AD drugs.

Repairing large tissue defects often represents a great challenge in clinics due to issues regarding lack of donors, mismatched sizes, irregular shapes, and immune rejection. Three-dimensional (3D) printed scaffolds are attractive for growing cells and producing tissue constructs because of the intricate control over pore size, porosity, and geometric shape, but the lack of biomimetic surface nanotopography and limited biomolecule presenting capacity render them less efficacious in regulating cell responses. Herein, we report, for the first time, a facile method for coating 3D printed scaffolds with electrospun nanofiber segments. The surface morphology of modified 3D scaffolds changes dramatically, displaying a biomimetic nanofibrous structure, while the bulk mechanical property, pore size and porosity are not significantly compromised. The short nanofibers-decorated 3D printed scaffolds significantly promote adhesion and proliferation of pre-osteoblasts and bone marrow mesenchymal stem cells (BMSCs). Further immobilization of bone morphogenetic protein-2 (BMP-2) mimicking peptides to nanofiber segments-decorated 3D printed scaffolds show enhanced mRNA expressions of osteogenic markers Runx2, Alp, OCN, and BSP in BMSCs, indicating the enhancement of BMSCs osteogenic differentiation. Together, the combination of 3D printing and electrospinning is a promising approach to greatly expand the functions of 3D printed scaffolds and enhance the efficacy of 3D printed scaffolds for tissue engineering.

Biomimetic and injectable nanofiber microspheres (NMs) could be ideal candidate for minimally invasive tissue repair. Herein, we report a facile approach to fabricate peptide-tethered NMs by combining electrospinning, electrospraying, and surface conjugation techniques. The composition and size of NMs can be tuned by varying the processing parameters during the fabrication. Further, bone morphogenic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) mimicking peptides have been successfully tethered onto poly(e-caprolactone) (PCL):gelatin:(gelatin-methacryloyl) (GelMA)(1:0.5:0.5) NMs through photocrosslinking of the methacrylic group in GelMA and octenyl alanine (OCTAL) in the modified peptides. The BMP-2-OCTAL peptide-tethered NMs significantly promote osteogenic differentiation of bone marrow-derived stem cells (BMSCs). Moreover, human umbilical vein endothelial cells (HUVECs) seeded on VEGF mimicking peptide QK-OCTAL-tethered NMs significantly up-regulated vascular-specific proteins, leading to microvascularization. The strategy developed in this work holds great potential in developing a biomimetic and injectable carrier to efficiently direct cellular response (Osteogenesis and Angiogenesis) for tissue repair.

Assembling electrospun nanofibers with controlled alignment into three-dimensional (3D), complex, and predesigned shapes has proven to be a difficult task for regenerative medicine. Herein, we report a novel approach inspired by solids of revolution that transforms two-dimensional (2D) nanofiber mats of a controlled thickness into once-inaccessible 3D objects with predesigned shapes. The 3D objects are highly porous, consisting of layers of aligned nanofibers separated by gaps ranging from several micrometers to several millimeters. Upon compression, the objects are able to recover their original shapes. The porous objects can serve as scaffolds, guiding the organization of cells and producing highly ordered 3D tissue constructs. Additionally, subcutaneous implantation in rats demonstrates that the 3D objects enable rapid cell penetration, new blood vessel formation, and collagen matrix deposition. This new class of 3D hierarchical nanofiber architectures offers promising advancements in both in vitro engineering of complex 3D tissue constructs/models or organs and in vivo tissue repair and regeneration.

A new approach is described for fabricating three-dimensional (3D) poly(ε-caprolactone) (PCL)/gelatin (1:1) nanofiber aerogels with patterned macrochannels and anisotropic microchannels by freeze-casting with 3D-printed sacrificial templates. Single layer or multiple layers of macrochannels are formed through an inverse replica of 3D-printed templates. Aligned microchannels formed by partially anisotropic freezing act as interconnected pores between templated macrochannels. The resulting macro/microchannels within nanofiber aerogels significantly increase pre-osteoblast infiltration in vitro. The conjugation of vascular endothelial growth factor (VEGF)-mimicking QK peptide to PCL/gelatin/gelatin methacryloyl (1:0.5:0.5) nanofiber aerogels with patterned macrochannels promote the formation of a microvascular network of seeded human microvascular endothelial cells. Moreover, nanofiber aerogels with patterned macrochannels and anisotropic microchannels show significantly enhanced cellular infiltration rates and host tissue integration compared to aerogels without macrochannels following subcutaneous implantation in rats. Taken together, this novel class of nanofiber aerogels holds great potential in biomedical applications including tissue repair and regeneration, wound healing, and 3D tissue/disease modeling.

Biofilms pose a major challenge to control wound-associated infections. Due to biofilm impenetrability, traditional antimicrobial agents are often ineffective in combating biofilms. Herein, we reported a biphasic scaffold as an antimicrobial delivery system by integrating nanofiber mats with dissolvable microneedle arrays for the effective treatment of bacterial biofilms. Different combinations of antimicrobial agents, including AgNO(3), Ga(NO(3))(3), and vancomycin, were incorporated into nanofiber mats by co-axial electrospinning, which enabled sustained delivery of these drugs. The antimicrobial agents-incorporated dissolvable microneedle arrays allowed direct penetration of drugs into biofilms. By optimizing the administration strategies, drug combinations, and microneedle densities, biphasic scaffolds were able to eradicate both methicillin-resistant Staphylococcus aureus (MRSA) and MRSA/Pseudomonas aeruginosa blend biofilms in an ex vivo human skin wound infection model without necessitating surgical debridement. Taken together, the combinatorial system comprised of nanofiber mats and microneedle arrays can provide an efficacious delivery of multiple antimicrobial agents for the treatment of bacterial biofilms in wounds.

The ability to transform two-dimensional (2D) structures into three-dimensional (3D) structures leads to a variety of applications in fields such as soft electronics, soft robotics, and other biomedical-related fields. Previous reports have focused on using electrospun nanofibers due to their ability to mimic the extracellular matrix. These studies often lead to poor results due to the dense structures and small poor sizes of 2D nanofiber membranes. Using a unique method of combining innovative gas-foaming and molding technologies, we report the rapid transformation of 2D nanofiber membranes into predesigned 3D scaffolds with biomimetic and oriented porous structure. By adding a surfactant (pluronic F-127) to poly(ε-caprolactone) (PCL) nanofibers, the rate of expansion is dramatically enhanced due to the increase in hydrophilicity and subsequent gas bubble stability. Using this novel method together with molding, 3D objects with cylindrical, hollow cylindrical, cuboid, spherical, and irregular shapes are created. Interestingly, these 3D shapes exhibit anisotropy and consistent pore sizes throughout entire object. Through further treatment with gelatin, the scaffolds become superelastic and shape-recoverable. Additionally, gelatin-coated, cube-shaped scaffolds were further functionalized with polypyrrole coatings and exhibited dynamic electrical conductivity during cyclic compression. Cuboid-shaped scaffolds have been demonstrated to be effective for compressible hemorrhage in a porcine liver injury model. In addition, human neural progenitor cells can be uniformly distributed and differentiated into neurons throughout the cylinder-shaped nanofiber scaffolds, forming ordered 3D neural tissue constructs. Taken together, the approach presented in this study is very promising in the production of pre-molded 3D nanofiber scaffolds for many biomedical applications.

Chronic wounds are one of the most devastating complications of diabetes and are the leading cause of nontraumatic limb amputation. Despite the progress in identifying factors and promising in vitro results for the treatment of chronic wounds, their clinical translation is limited. Given the range of disruptive processes necessary for wound healing, different pharmacological agents are needed at different stages of tissue regeneration. This requires the development of wearable devices that can deliver agents to critical layers of the wound bed in a minimally invasive fashion. Here, for the first time, a programmable platform is engineered that is capable of actively delivering a variety of drugs with independent temporal profiles through miniaturized needles into deeper layers of the wound bed. The delivery of vascular endothelial growth factor (VEGF) through the miniaturized needle arrays demonstrates that, in addition to the selection of suitable therapeutics, the delivery method and their spatial distribution within the wound bed is equally important. Administration of VEGF to chronic dermal wounds of diabetic mice using the programmable platform shows a significant increase in wound closure, re-epithelialization, angiogenesis, and hair growth when compared to standard topical delivery of therapeutics.

The logistics of the current Australian and Californian recommendations to harvest avocado below 30 °C and remove field heat within 6 hours of harvest are increasingly being challenged as the Western Australian industry expands. Despite this, there has been little feedback of quality sacrifice in the market as a result. Through factorial experiments, we harvested both shaded and sun-exposed 'Hass' avocado over an ambient air temperature range of 27-34 °C, subjected to a 2, 6 or 24 h pre-cooling delay and a 14 or 28 day cool-storage, before ripening and quality assessment. We found significant temperature correlations to softening, vascular browning, body rots and, when a temperature-by-delay interaction was considered, skin colour. The relationships of temperature to softening and body rot were quadratic: softening increased significantly up to an ambient temperature of about 30 °C but did not change significantly thereafter; body rots did not change significantly up to 30 °C but declined significantly thereafter. The interaction effect of temperature-by-delay on colour was also quadratic when fruit were subjected to a 24 h pre-cooling delay. Fruit colour increased significantly up to about 30 °C but did not change significantly thereafter. The relationship of temperature to vascular browning was negatively linear; showing a significant decline over the range of 27-34 °C. There was no significant main effect of sun-exposure, although there were significant interactions; showing that postharvest behaviour varied between shaded and sun-exposed fruit. However, the average elevation of 6 °C above shaded fruit temperatures was not as large as reported by previous studies and was thus interpreted with caution. In light of the results, experiments have been designed to further explore the main effects and interactions of temperature, sunlight, and postharvest handling on avocado quality and physiology.

The ability to tune supramolecular properties such as size, morphology, or metabolic stability is of paramount importance in the field of supramolecular chemistry. Peptide amphiphiles (PAs) are a family of functional self-assembling biomaterials that have garnered widespread attention due to their broad applicability in medicine. PAs are generally comprised of an amino acid sequence connected to lipid tail(s) allowing them to self-assemble into supramolecular structures with diverse morphologies. Herein, this study describes the synthesis of a new class of polyamine-based "hybrid" PAs (PPAs) as novel self-assembling systems. The described molecules possess diverse polyamine head groups with the goal of tuning physicochemical properties. The findings indicate that small changes in the polyamine head groups result in altered PPA morphologies (nanofibers, micelles, nanoworms). The PPAs present a wide range of physicochemical characteristics, show superior resistance to aggregation, a diverse metabolic profile, and varied assembling kinetics. Most of the PPAs do not show toxicity in the human cells lines evaluated. The PPAs described herein hold promising potential as a safe and nontoxic option for drug delivery, targeting, and tissue engineering applications.