Antibacterial anti-oxidant electroactive injectable hydrogel as self-healing wound dressing with hemostasis and adhesiveness for cutaneous wound healing

Electrospinning of polymeric nanofibers for drug delivery applications

Stem cells and their local microenvironment, or niche, communicate through mechanical cues to regulate cell fate and cell behaviour and to guide developmental processes. During embryonic development, mechanical forces are involved in patterning and organogenesis. The physical environment of pluripotent stem cells regulates their self-renewal and differentiation. Mechanical and physical cues are also important in adult tissues, where adult stem cells require physical interactions with the extracellular matrix to maintain their potency. In vitro, synthetic models of the stem cell niche can be used to precisely control and manipulate the biophysical and biochemical properties of the stem cell microenvironment and to examine how the mode and magnitude of mechanical cues, such as matrix stiffness or applied forces, direct stem cell differentiation and function. Fundamental insights into the mechanobiology of stem cells also inform the design of artificial niches to support stem cells for regenerative therapies.

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Mechanical forces direct stem cell behaviour in development and regeneration

Substantial research over the past two decades has established that extracellular matrix (ECM) elasticity, or stiffness, affects fundamental cellular processes, including spreading, growth, proliferation, migration, differentiation and organoid formation. Linearly elastic polyacrylamide hydrogels and polydimethylsiloxane (PDMS) elastomers coated with ECM proteins are widely used to assess the role of stiffness, and results from such experiments are often assumed to reproduce the effect of the mechanical environment experienced by cells in vivo. However, tissues and ECMs are not linearly elastic materials-they exhibit far more complex mechanical behaviours, including viscoelasticity (a time-dependent response to loading or deformation), as well as mechanical plasticity and nonlinear elasticity. Here we review the complex mechanical behaviours of tissues and ECMs, discuss the effect of ECM viscoelasticity on cells, and describe the potential use of viscoelastic biomaterials in regenerative medicine. Recent work has revealed that matrix viscoelasticity regulates these same fundamental cell processes, and can promote behaviours that are not observed with elastic hydrogels in both two- and three-dimensional culture microenvironments. These findings have provided insights into cell-matrix interactions and how these interactions differentially modulate mechano-sensitive molecular pathways in cells. Moreover, these results suggest design guidelines for the next generation of biomaterials, with the goal of matching tissue and ECM mechanics for in vitro tissue models and applications in regenerative medicine.

Effects of extracellular matrix viscoelasticity on cellular behaviour.

Over centuries, the field of regenerative skin tissue engineering has had several advancements to facilitate faster wound healing and thereby restoration of skin. Skin tissue regeneration is mainly based on the use of suitable scaffold matrices. There are several scaffold types, such as porous, fibrous, microsphere, hydrogel, composite and acellular, etc., with discrete advantages and disadvantages. These scaffolds are either made up of highly biocompatible natural biomaterials, such as collagen, chitosan, etc., or synthetic materials, such as polycaprolactone (PCL), and poly-ethylene-glycol (PEG), etc. Composite scaffolds, which are a combination of natural or synthetic biomaterials, are highly biocompatible with improved tensile strength for effective skin tissue regeneration. Appropriate knowledge of the properties, advantages and disadvantages of various biomaterials and scaffolds will accelerate the production of suitable scaffolds for skin tissue regeneration applications. At the same time, emphasis on some of the leading challenges in the field of skin tissue engineering, such as cell interaction with scaffolds, faster cellular proliferation/differentiation, and vascularization of engineered tissues, is inevitable. In this review, we discuss various types of scaffolding approaches and biomaterials used in the field of skin tissue engineering and more importantly their future prospects in skin tissue regeneration efforts.

https://www.mdpi.com/1422-0067/17/12/1974/pdf

Future Prospects for Scaffolding Methods and Biomaterials in Skin Tissue Engineering: A Review

Current strategies to treat chronic wounds offer limited relief to the 7.75 million patients who suffer from burns or chronic skin ulcers. Thus, as long as chronic wounds remain a global healthcare problem, the development of alternate treatments remain desperately needed. This review explores the recent strategies employed to tailor electrospun nanofiber mats towards accelerating the wound healing process. Porous nanofiber mats readily produced by the electrospinning process offer a promising solution to the management of wounds. The matrix chemistry, surface functionality, and mat degradation rate all can be fine-tuned to govern the interactions that occur at the materials-biology interface. In this review, first we briefly discuss the wound healing process and then highlight recent advances in drug release, biologics encapsulation, and antibacterial activity that have been demonstrated via electrospinning. While this versatile biomaterial has shown much progress, commercializing nanofiber mats that fully address the needs of an individual patient remains an ambitious challenge.

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Designing electrospun nanofiber mats to promote wound healing – a review

The current knowledge of bone marrow mechanics is limited to its viscous properties, neglecting the elastic contribution of the extracellular matrix. To get a more complete view of the mechanics of marrow, we characterized intact yellow porcine bone marrow using three different, but complementary techniques: rheology, indentation, and cavitation. Our analysis shows that bone marrow is elastic, and has a large amount of intra- and inter-sample heterogeneity, with an effective Young׳s modulus ranging from 0.25 to 24.7 kPa at physiological temperature. Each testing method was consistent across matched tissue samples, and each provided unique benefits depending on user needs. We recommend bulk rheology to capture the effects of temperature on tissue elasticity and moduli, indentation for quantifying local tissue heterogeneity, and cavitation rheology for mitigating destructive sample preparation. We anticipate the knowledge of bone marrow elastic properties for building in vitro models will elucidate mechanisms involved in disease progression and regenerative medicine.

https://scholarworks.umass.edu/cgi/viewcontent.cgi?article=1848&context=che_faculty_pubs

Mechanics of intact bone marrow

Chronic wounds continue to be a global healthcare concern. Thus, the development of new nanoparticle-based therapies that treat multiple symptoms of these "non-healing" wounds without encouraging antibiotic resistance is imperative. One potential solution is to use chitosan, a naturally antimicrobial polycation, which can spontaneously form polyelectrolyte complexes when mixed with a polyanion in appropriate aqueous conditions. The requirement of at least two different polymers opens up the opportunity for us to form chitosan complexes with an additional functional polyanion. In this study, chitosan:pectin (CS:Pec) nanoparticles were synthesized using an aqueous spontaneous ionic gelation method. Systematically, a number of parameters, polymer concentration, addition order, mass ratio, and solution pH, were explored and their effect on nanoparticle formation was determined. The size and surface charge of the particles were characterized, as well as their morphology using transmission electron microscopy. The effect of polymer concentration and addition order on the nanoparticles was found to be similar to that of other chitosan:polyanion complexes. The mass ratio was tuned to create nanoparticles with a chitosan shell and a controllable positive zeta potential. The particles were stable in a pH range from 3.5 to 6.0 and lost stability after 14 days of storage in aqueous media. Due to the high positive surface charge of the particles, the innate properties of the polysaccharides used, and the harmless disassociation of the polyelectrolytes, we suggest that the development of these CS:Pec nanoparticles offers great promise as a chronic wound healing platform.

Characterization of self-assembled polyelectrolyte complex nanoparticles formed from chitosan and pectin.

Electrospinning chitosan/poly(ethylene oxide) solutions with essential oils: Correlating solution rheology to nanofiber formation

Published data on the mechanical strength and elasticity of lung tissue is widely variable, primarily due to differences in how testing was conducted across individual studies. This makes it extremely difficult to find a benchmark modulus of lung tissue when designing synthetic extracellular matrices (ECMs). To address this issue, we tested tissues from various areas of the lung using multiple characterization techniques, including micro-indentation, small amplitude oscillatory shear (SAOS), uniaxial tension, and cavitation rheology. We report the sample preparation required and data obtainable across these unique but complimentary methods to quantify the modulus of lung tissue. We highlight cavitation rheology as a new method, which can measure the modulus of intact tissue with precise spatial control, and reports a modulus on the length scale of typical tissue heterogeneities. Shear rheology, uniaxial, and indentation testing require heavy sample manipulation and destruction; however, cavitation rheology can be performed in situ across nearly all areas of the lung with minimal preparation. The Young’s modulus of bulk lung tissue using micro-indentation (1.4±0.4 kPa), SAOS (3.3±0.5 kPa), uniaxial testing (3.4±0.4 kPa), and cavitation rheology (6.1±1.6 kPa) were within the same order of magnitude, with higher values consistently reported from cavitation, likely due to our ability to keep the tissue intact. Although cavitation rheology does not capture the non-linear strains revealed by uniaxial testing and SAOS, it provides an opportunity to measure mechanical characteristics of lung tissue on a microscale level on intact tissues. Overall, our study demonstrates that each technique has independent benefits, and each technique revealed unique mechanical features of lung tissue that can contribute to a deeper understanding of lung tissue mechanics.

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Nathan P. Birch

Papers

Designing electrospun nanofiber mats to promote wound healing – a review

Mechanics of intact bone marrow

Characterization of self-assembled polyelectrolyte complex nanoparticles formed from chitosan and pectin.

Electrospinning chitosan/poly(ethylene oxide) solutions with essential oils: Correlating solution rheology to nanofiber formation

Cross-platform mechanical characterization of lung tissue