Biomaterials for immunomodulation in wound healing.

The substantial economic impact of non-healing wounds, scarring, and burns stemming from skin injuries is evident, resulting in a financial burden on both patients and the healthcare system. This review paper provides an overview of the skin's vital role in guarding against various environmental challenges as the body's largest protective organ and associated developments in biomaterials for wound healing. We first introduce the composition of skin tissue and the intricate processes of wound healing, with special attention to the crucial role of immunomodulation in both acute and chronic wounds. This highlights how the imbalance in the immune response, particularly in chronic wounds associated with underlying health conditions such as diabetes and immunosuppression, hinders normal healing stages. Then, this review distinguishes between traditional wound-healing strategies that create an optimal microenvironment and recent peptide-based biomaterials that modulate cellular processes and immune responses to facilitate wound closure. Additionally, we highlight the importance of considering the stages of wounds in the healing process. By integrating advanced materials engineering with an in-depth understanding of wound biology, this approach holds promise for reshaping the field of wound management and ultimately offering improved outcomes for patients with acute and chronic wounds.

Comprehensive fluorescence profiles of contamination-prone foods applied to the design of microcontact-printed in situ functional oligonucleotide sensors.

With both foodborne illness and food spoilage detrimentally impacting human health and the economy, there is growing interest in the development of in situ sensors that offer real-time monitoring of food quality within enclosed food packages. While oligonucleotide-based fluorescent sensors have illustrated significant promise, the development of such on-food sensors requires consideration towards sensing-relevant fluorescence properties of target food products-information that has not yet been reported. To address this need, comprehensive fluorescence profiles for various contamination-prone food products are established in this study across several wavelengths and timepoints. The intensity of these food backgrounds is further contextualized to biomolecule-mediated sensing using overlaid fluorescent oligonucleotide arrays, which offer perspective towards the viability of distinct wavelengths and fluorophores for in situ food monitoring. Results show that biosensing in the Cyanine3 range is optimal for all tested foods, with the Cyanine5 range offering comparable performance with meat products specifically. Moreover, recognizing that mass fabrication of on-food sensors requires rapid and simple deposition of sensing agents onto packaging substrates, RNA-cleaving fluorescent nucleic acid probes are successfully deposited via microcontact printing for the first time. Direct incorporation onto food packaging yields cost-effective sensors with performance comparable to ones produced using conventional deposition strategies.

Advances in cardiac tissue engineering and heart-on-a-chip.

Recent advances in both cardiac tissue engineering and hearts-on-a-chip are grounded in new biomaterial development as well as the employment of innovative fabrication techniques that enable precise control of the mechanical, electrical, and structural properties of the cardiac tissues being modelled. The elongated structure of cardiomyocytes requires tuning of substrate properties and application of biophysical stimuli to drive its mature phenotype. Landmark advances have already been achieved with induced pluripotent stem cell-derived cardiac patches that advanced to human testing. Heart-on-a-chip platforms are now commonly used by a number of pharmaceutical and biotechnology companies. Here, we provide an overview of cardiac physiology in order to better define the requirements for functional tissue recapitulation. We then discuss the biomaterials most commonly used in both cardiac tissue engineering and heart-on-a-chip, followed by the discussion of recent representative studies in both fields. We outline significant challenges common to both fields, specifically: scalable tissue fabrication and platform standardization, improving cellular fidelity through effective tissue vascularization, achieving adult tissue maturation, and ultimately developing cryopreservation protocols so that the tissues are available off the shelf.

Engineering Organ-on-a-Chip Systems for Vascular Diseases.

Vascular diseases, such as atherosclerosis and thrombosis, are major causes of morbidity and mortality worldwide. Traditional in vitro models for studying vascular diseases have limitations, as they do not fully recapitulate the complexity of the in vivo microenvironment. Organ-on-a-chip systems have emerged as a promising approach for modeling vascular diseases by incorporating multiple cell types, mechanical and biochemical cues, and fluid flow in a microscale platform. This review provides an overview of recent advancements in engineering organ-on-a-chip systems for modeling vascular diseases, including the use of microfluidic channels, ECM (extracellular matrix) scaffolds, and patient-specific cells. We also discuss the limitations and future perspectives of organ-on-a-chip for modeling vascular diseases.

Elastomeric Polyesters in Cardiovascular Tissue Engineering and Organs-on-a-Chip.

Cardiovascular tissue constructs provide unique design requirements due to their functional responses to substrate mechanical properties and cyclic stretching behavior of cardiac tissue that requires the use of durable elastic materials. Given the diversity of polyester synthesis approaches, an opportunity exists to develop a new class of biocompatible, elastic, and immunomodulatory cardiovascular polymers. Furthermore, elastomeric polyester materials have the capability to provide tailored biomechanical synergy with native tissue and hence reduce inflammatory response in vivo and better support tissue maturation in vitro. In this review, we highlight underlying chemistry and design strategies of polyester elastomers optimized for cardiac tissue scaffolds. The major advantages of these materials such as their tunable elasticity, desirable biodegradation, and potential for incorporation of bioactive compounds are further expanded. Unique fabrication methods using polyester materials such as micromolding, 3D stamping, electrospinning, laser ablation, and 3D printing are discussed. Moreover, applications of these biomaterials in cardiovascular organ-on-a-chip devices and patches are analyzed. Finally, we outline unaddressed challenges in the field that need further study to enable the impactful translation of soft polyesters to clinical applications.

Advancing In Situ Food Monitoring through a Smart Lab-in-a-Package System Demonstrated by the Detection of Salmonella in Whole Chicken.

With food production shifting away from traditional farm-to-table approaches to efficient multistep supply chains, the incidence of food contamination has increased. Consequently, pathogen testing via inefficient culture-based methods has increased, despite its lack of real-time capabilities and need for centralized facilities. While in situ pathogen detection would address these limitations and enable individual product monitoring, accurate detection within unprocessed, packaged food products without user manipulation has proven elusive. Herein, "Lab-in-a-Package" is presented, a platform capable of sampling, concentrating, and detecting target pathogens within closed food packaging, without intervention. This system consists of a newly designed packaging tray and reagent-infused membrane that can be paired universally with diverse pathogen sensors. The inclined food packaging tray maximizes fluid localization onto the sensing interface, while the membrane acts as a reagent-immobilizing matrix and an antifouling barrier for the sensor. The platform is substantiated using a newly discovered Salmonella-responsive nucleic acid probe, which enables hands-free detection of 103 colony forming units (CFU) g-1 target pathogen in a packaged whole chicken. The platform remains effective when contamination is introduced with toolsand surfaces, ensuring widespread efficacy. Its real-world use for in situ detection is simulated using a handheld fluorescence scanner with smartphone connectivity.

A Bifunctional Spray Coating Reduces Contamination on Surfaces by Repelling and Killing Pathogens.

Surface-mediated transmission of pathogens is a major concern with regard to the spread of infectious diseases. Current pathogen prevention methods on surfaces rely on the use of biocides, which aggravate the emergence of antimicrobial resistance and pose harmful health effects. In response, a bifunctional and substrate-independent spray coating is presented herein. The bifunctional coating relies on wrinkled polydimethylsiloxane microparticles, decorated with biocidal gold nanoparticles to induce a "repel and kill" effect against pathogens. Pathogen repellency is provided by the structural hierarchy of the microparticles and their surface chemistry, whereas the kill mechanism is achieved using functionalized gold nanoparticles embedded on the microparticles. Bacterial tests with methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa reveal a 99.9% reduction in bacterial load on spray-coated surfaces, while antiviral tests with Phi6─a bacterial virus often used as a surrogate to SARS-CoV-2─demonstrate a 98% reduction in virus load on coated surfaces. The newly developed spray coating is versatile, easily applicable to various surfaces, and effective against various pathogens, making it suitable for reducing surface contamination in frequently touched, heavy traffic, and high-risk surfaces.

An Omniphobic Spray Coating Created from Hierarchical Structures Prevents the Contamination of High-Touch Surfaces with Pathogens.

Engineered surfaces that repel pathogens are of great interest due to their role in mitigating the spread of infectious diseases. A robust, universal, and scalable omniphobic spray coating with excellent repellency against water, oil, and pathogens is presented. The coating is substrate-independent and relies on hierarchically structured polydimethylsiloxane (PDMS) microparticles, decorated with gold nanoparticles (AuNPs). Wettability studies reveal the relationship between surface texturing of micro- and/or nano-hierarchical structures and the omniphobicity of the coating. Studies of pathogen transfer with bacteria and viruses reveal that an uncoated contaminated glove transfers pathogens to >50 subsequent surfaces, while a coated glove picks up 104 (over 99.99%) less pathogens upon first contact and transfers zero pathogens after the second touch. The developed coating also provides excellent stability under harsh conditions. The remarkable anti-pathogen properties of this surface combined with its ease of implementation, substantiate its use for the prevention of surface-mediated transmission of pathogens.

The Fabrication and Bonding of Thermoplastic Microfluidics: A Review.

Various fields within biomedical engineering have been afforded rapid scientific advancement through the incorporation of microfluidics. As literature surrounding biological systems become more comprehensive and many microfluidic platforms show potential for commercialization, the development of representative fluidic systems has become more intricate. This has brought increased scrutiny of the material properties of microfluidic substrates. Thermoplastics have been highlighted as a promising material, given their material adaptability and commercial compatibility. This review provides a comprehensive discussion surrounding recent developments pertaining to thermoplastic microfluidic device fabrication. Existing and emerging approaches related to both microchannel fabrication and device assembly are highlighted, with consideration toward how specific approaches induce physical and/or chemical properties that are optimally suited for relevant real-world applications.

Contamination and carryover free handling of complex fluids using lubricant-infused pipette tips.

Cross-contamination of biological samples during handling and preparation, is a major issue in laboratory setups, leading to false-positives or false-negatives. Sample carryover residue in pipette tips contributes greatly to this issue. Most pipette tips on the market are manufactured with hydrophobic polymers that are able to repel high surface tension liquids, yet they lack in performance when low surface tension liquids and viscous fluids are involved. Moreover, hydrophobicity of pipette tips can result in hydrophobic adsorption of biomolecules, causing inaccuracies and loss in precision during pipetting. Here we propose the use of lubricant-infused surface (LIS) technology to achieve omniphobic properties in pipette tips. Using a versatile and simple design, the inner lumen of commercially available pipette tips was coated with a fluorosilane (FS) layer using chemical vapor deposition (CVD). The presence of FS groups on the tips is confirmed by x-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) tests. After lubrication of the tips through a fluorinated lubricant, the omniphobicity and repellent behaviour of the tips drastically enhanced which are revealed via static and hysteresis contact angle measurements. The repellency of the lubricant-infused pipette tips against physical adsorption is investigated through pipetting a food coloring dye as well as human blood samples and are compared to the untreated tips. The results show significantly less amount carryover residue when the lubricant-infused tips are utilized compared to commercially available ones. We also demonstrate the lubricant-infused tips reduce bacteria contamination of the inner lumen by 3 to 6-log (over 99%, depending on the tip size) after pipetting up and down the bacteria solution.

Bio-functionalization of microfluidic platforms made of thermoplastic materials: A review.

As a result of their favorable physical and chemical characteristics, thermoplastics have garnered significant interest in the area of microfluidics. The moldable nature of these inexpensive polymers enables easy fabrication, while their durability and chemical stability allow for resistance to high shear stress conditions and functionalization, respectively. This review provides a comprehensive examination several commonly used thermoplastic polymers in the microfluidics space including poly(methyl methacrylate) (PMMA), cyclic olefin polymer (COP) and copolymer (COC), polycarbonates (PC), poly(ethylene terephthalate) (PET), polystyrene (PS), poly(ethylene glycol) (PEG), polylactic acid (PLA), acrylonitrile butadiene styrene (ABS), and polyester. We describe various biofunctionalization strategies applied within thermoplastic microfluidic platforms and their resultant applications. Lastly, emerging technologies with a focus on applying recently developed microfluidic and biofunctionalization strategies into thermoplastic systems are discussed.

Transparent and Highly Flexible Hierarchically Structured Polydimethylsiloxane Surfaces Suppress Bacterial Attachment and Thrombosis Under Static and Dynamic Conditions.

The surface fouling of biomedical devices has been an ongoing issue in healthcare. Bacterial and blood adhesion in particular, severely impede the performance of such tools, leading to poor patient outcomes. Various structural and chemical modifications have been shown to reduce fouling, but all existing strategies lack the combination of physical, chemical, and economic traits necessary for widespread use. Herein, a lubricant infused, hierarchically micro- and nanostructured polydimethylsiloxane surface is presented. The surface is easy to produce and exhibits the high flexibility and optical transparency necessary for incorporation into various biomedical tools. Tests involving two clinically relevant, priority pathogens show up to a 98.5% reduction in the biofilm formation of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. With blood, the surface reduces staining by 95% and suppresses thrombin generation to background levels. Furthermore, the surface shows applicability within applications such as catheters, extracorporeal circuits, and microfluidic devices, through its effectiveness in dynamic conditions. The perfusion of bacterial media shows up to 96.5% reduction in bacterial adhesion. Similarly, a 95.8% reduction in fibrin networks is observed following whole blood perfusion. This substrate stands to hold high applicability within biomedical systems as a means to prevent fouling, thus improving performance.

Producing Fluorine- and Lubricant-Free Flexible Pathogen- and Blood-Repellent Surfaces Using Polysiloxane-Based Hierarchical Structures.

High-touch surfaces are known to be a major route for the spread of pathogens in healthcare and public settings. Antimicrobial coatings have, therefore, garnered significant attention to help mitigate the transmission of infectious diseases via the surface route. Among antimicrobial coatings, pathogen-repellent surfaces provide unique advantages in terms of safety in public settings such as instant repellency, affordability, biocompatibility, and long-term stability. While there have been many advances in the fabrication of biorepellent surfaces in the past two decades, this area of research continues to suffer challenges in scalability, cost, compatibility with high-touch applications, and performance for pathogen repellency. These features are critical for high-touch surfaces to be used in public settings. Additionally, the environmental impact of manufacturing repellent surfaces remains a challenge, mainly due to the use of fluorinated coatings. Here, we present a flexible hierarchical coating with straightforward and cost-effective manufacturing without the use of fluorine or a lubricant. Hierarchical surfaces were prepared through the growth of polysiloxane nanostructures using n-propyltrichlorosilane (n-PTCS) on activated polyolefin (PO), followed by heat shrinking to induce microscale wrinkles. The developed coatings demonstrated repellency, with contact angles over 153° and sliding angles <1°. In assays mimicking touch, these hierarchical surfaces demonstrated a 97.5% reduction in transmission of Escherichia coli (E.coli), demonstrating their potential as antimicrobial coatings to mitigate the spread of infectious diseases. Additionally, the developed surfaces displayed a 93% reduction in blood staining after incubation with human whole blood, confirming repellent properties that reduce bacterial deposition.

LISzyme Biosensors: DNAzymes Embedded in an Anti-biofouling Platform for Hands-free Real-Time Detection of Bacterial Contamination in Milk.

Nonspecific binding is a significant challenge associated with biosensors in complex food textures. To overcome this, we have developed LISzymes, which are DNAzymes incorporated in lubricant-infused surfaces (LISs). Using milk as a complex background matrix, we show that LISzyme biosensors are significantly more effective in preventing nonspecific binding compared to other commonly used "blocking" methods. The use of lubricant infusion to treat sensing surfaces results in a 4-fold increase in the signal-to-noise ratio obtained with the DNAzyme with respect to untreated surfaces, when detecting the presence of specific bacteria in milk. This is a striking improvement upon previous DNAzyme sensors. We also show that the use of LISs does not affect the DNAzyme's ability to effectively and specifically detect its target─a protein specifically produced by Escherichia coli (E. coli), in a complex sample matrix such as milk. LISzymes drastically improve DNAzyme performance, resulting in target detection associated with E. coli at concentrations as low as 250 CFU/mL in milk in less than an hour, which is currently not possible using other optical platforms. LISzymes are promising tools for the real-time monitoring of food contamination and may prove valuable within many other biosensing applications.

Conventional and emerging strategies for the fabrication and functionalization of PDMS-based microfluidic devices.

Microfluidics is an emerging and multidisciplinary field that is of great interest to manufacturers in medicine, biotechnology, and chemistry, as it provides unique tools for the development of point-of-care diagnostics, organs-on-chip systems, and biosensors. Polymeric microfluidics, unlike glass and silicon, offer several advantages such as low-cost mass manufacturing and a wide range of beneficial material properties, which make them the material of choice for commercial applications and high-throughput systems. Among polymers used for the fabrication of microfluidic devices, polydimethylsiloxane (PDMS) still remains the most widely used material in academia due to its advantageous properties, such as excellent transparency and biocompatibility. However, commercialization of PDMS has been a challenge mostly due to the high cost of the current fabrication strategies. Moreover, specific surface modification and functionalization steps are required to tailor the surface chemistry of PDMS channels (e.g. biomolecule immobilization, surface hydrophobicity and antifouling properties) with respect to the desired application. While significant research has been reported in the field of PDMS microfluidics, functionalization of PDMS surfaces remains a critical step in the fabrication process that is difficult to navigate. This review first offers a thorough illustration of existing fabrication methods for PDMS-based microfluidic devices, providing several recent advancements in this field with the aim of reducing the cost and time for mass production of these devices. Next, various conventional and emerging approaches for engineering the surface chemistry of PDMS are discussed in detail. We provide a wide range of functionalization techniques rendering PDMS microchannels highly biocompatible for physical or covalent immobilization of various biological entities while preventing non-specific interactions.

Hierarchical Structures, with Submillimeter Patterns, Micrometer Wrinkles, and Nanoscale Decorations, Suppress Biofouling and Enable Rapid Droplet Digitization.

Liquid repellant surfaces have been shown to play a vital role for eliminating thrombosis on medical devices, minimizing blood contamination on common surfaces as well as preventing non-specific adhesion. Herein, an all solution-based, easily scalable method for producing liquid repellant flexible films, fabricated through nanoparticle deposition and heat-induced thin film wrinkling that suppress blood adhesion, and clot formation is reported. Furthermore, superhydrophobic and hydrophilic surfaces are combined onto the same substrate using a facile streamlined process. The patterned superhydrophobic/hydrophilic surfaces show selective digitization of droplets from various solutions with a single solution dipping step, which provides a route for rapid compartmentalization of solutions into virtual wells needed for high-throughput assays. This rapid solution digitization approach is demonstrated for detection of Interleukin 6. The developed liquid repellant surfaces are expected to find a wide range of applications in high-throughput assays and blood contacting medical devices.

Antibody Micropatterned Lubricant-Infused Biosensors Enable Sub-Picogram Immunofluorescence Detection of Interleukin 6 in Human Whole Plasma.

Recent studies have shown a correlation between elevated interleukin 6 (IL-6) concentrations and the risk of respiratory failure in COVID-19 patients. Therefore, detection of IL-6 at low concentrations permits early diagnosis of worst-case outcome in viral respiratory infections. Here, a versatile biointerface is presented that eliminates nonspecific adhesion and thus enables immunofluorescence detection of IL-6 in whole human plasma or whole human blood during coagulation, down to a limit of detection of 0.5 pg mL-1 . The sensitivity of the developed lubricant-infused biosensor for immunofluorescence assays in detecting low molecular weight proteins such as IL-6 is facilitated by i) producing a bioink in which the capture antibody is functionalized by an epoxy-based silane for covalent linkage to the fluorosilanized surface and ii) suppressing nonspecific adhesion by patterning the developed bioink into a lubricant-infused coating. The developed biosensor addresses one of the major challenges for biosensing in complex fluids, namely nonspecific adhesion, therefore paving the way for highly sensitive biosensing in complex fluids.

Plasma-induced covalent immobilization and patterning of bioactive species in microfluidic devices.

Here, we present a straightforward technique to create bio-functional microfluidic channels using CO2 plasma to induce both carboxylic and hydroxyl groups onto the channel surface. Consequently, not only does the surface allow for irreversible covalent bonding to an oxygen plasma treated PDMS for microfluidic device fabrication, but it also provides functionality for biomolecular immobilization. Furthermore, we demonstrate integration of this technique with microcontact printing to covalently micropattern functional biomolecules inside microfluidic channels. The bio-functionality and efficacy of the microcontact printed antibodies is demonstrated for both bioassays as well as patterning and culturing different cell lines. Results show that the introduced method can be an excellent candidate for cell culture studies in microfluidics. With the new printing method, full cell confluency (∼400 cells per mm2) was achieved after incubation for only 1 day, which is significantly greater than other conventional cell culture techniques inside microfluidic devices. As a proof of concept, we demonstrated the endothelial cells functionality by stimulating von Willebrand Factor secretion under shear stress. This is done via perfusion of histamine through the channel and performing immunofluorescence labeling to observe the inflammatory response of the cells. The developed method eliminates the need for wet chemistry and significantly simplifies producing bio-functional chips which can be used for biosensing, organs-on-chips and tissue engineering applications.

Micropatterned biofunctional lubricant-infused surfaces promote selective localized cell adhesion and patterning.

Micropatterned biofunctional surfaces provide a wide range of applications in bioengineering. A key characteristic which is sought in these types of bio-interfaces is prevention of non-specific adhesion for enhanced biofunctionality and targeted binding. Lubricant-infused omniphobic coatings have exhibited superior performance in attenuating non-specific adhesion; however, these coatings completely block the surfaces and do not support targeted adhesion or patterning. In this work, we introduce a novel lubricant-infused surface with biofunctional micropatterned domains integrated within an omniphobic layer. This new class of micropatterned lubricant-infused surfaces simultaneously promotes localized and directed binding of desired targets, as well as repellency of undesired species, especially in human whole blood. Furthermore, this modification method is easily translatable to microfluidic devices offering a wider range of applications and improved performance for immunoassays in whole blood and inhibition of clot formation in microfluidic channels. The biofunctional micropatterned lubricant-infused surfaces were created through a bench-top straight forward process by integrating microcontact printing, chemical vapor deposition (CVD) of self-assembled monolayers (SAMs) of fluorosilanes, and further infusion of the SAMs with a bio-compatible fluorocarbon-based lubricant layer. The developed surfaces, patterned with anti-CD34 antibodies, yield enhanced adhesion and controlled localized binding of target biomolecules (e.g. antibodies) and CD34 positive cells (e.g. HUVECs) inside microfluidic devices, outperforming conventional blocking methods (e.g. bovine serum albumin (BSA) or poly(ethylene glycol) (PEG)) in buffer and human whole blood. These surfaces offer a straightforward and effective way to enhance blocking capabilities while preserving the biofunctionality of a micropatterned system in complex biological environments such as whole blood. We anticipate that these micropatterned biofunctional interfaces will find a wide range of applications in microfluidic devices and biosensors for enhanced and localized targeted binding while preventing non-specific adhesion.

Suppression of Biofouling on a Permeable Membrane for Dissolved Oxygen Sensing Using a Lubricant-Infused Coating.

Specific ranges of dissolved oxygen (DO) concentrations must be maintained in a waterbody for it to be hospitable for aquatic animals. DO sensor designs can employ selectively permeable membranes to isolate DO from untargeted compounds or organisms in waterbodies. Hence, the DO concentration can be monitored and the health of the water can be evaluated over time. However, the presence of bacteria in natural waterbodies can lead to the formation of biofilms that can block pores and prevent analyte from permeating the membrane, resulting in inaccurate readings. In this work, we demonstrate the implementation of a fluorosilane-based omniphobic lubricant-infused (OLI) coating on a selectively permeable membrane and investigate the rate of biofilm formation for a commercially available DO sensor. Coated and unmodified membranes were incubated in an environment undergoing accelerated bacterial growth, and the change in sensitivity was evaluated after 40, 100, 250, and 500 h. Our findings show that the OLI membranes attenuate biofouling by 70% and maintain sensitivity after 3 weeks of incubation, further demonstrating that oxygen transfer through the OLI coating is achievable. Meanwhile, unmodified membranes exhibit significant biofouling that results in a 3.35 higher rate of decay in oxygen measurement sensitivity and an over 70% decrease in static contact angle. These results show that the OLI coating can be applied on commercially available membranes to prevent biofouling. Therefore, OLI coatings are a suitable candidate to suppress biofilm formation in the widespread use of selectively permeable membranes for environmental, medical, and fluid separation applications.