Macrophage Phenotypic Changes on FN-Coated Physical Gradient Hydrogels.

The chemical and physical properties are two crucial cues when designing tissue engineering scaffold to mimic living tissue. Macrophages, the major players in the immune response, react rapidly to microenvironmental signals, including gradients of physical or chemical cues. Spatiotemporal gradients can modulate cell behavior, such as polarization, proliferation, and adhesion.

Soft materials as biological and artificial membranes.

The past few decades have seen emerging growth in the field of soft materials for synthetic biology. This review focuses on soft materials involved in biological and artificial membranes. The biological membranes discussed here are mainly those involved in the structure and function of cells and organelles.

Gellan gum-gelatin viscoelastic hydrogels as scaffolds to promote fibroblast differentiation.

Fabricating hydrogel scaffolds that are both bioreactive toward fibroblasts while still mechanically compatible with surrounding tissue is a major challenge in tissue engineering. This is because the outcome of scaffold implantation is largely determined by fibroblasts differentiating toward myofibroblasts, which is characterized by the expression of α-smooth muscle actin (α-SMA). Previous studies promoted fibroblasts differentiation by increasing scaffold substrate stiffness.

Effect of RGD functionalization and stiffness of gellan gum hydrogels on macrophage polarization and function.

Macrophages, the primary effector cells in the immune response, respond rapidly to the physical or chemical properties of biomaterial implants. Balanced macrophage polarization, phagocytosis, and migration would be beneficial for implant success and tissue regeneration. Here, we investigated macrophage phenotypic changes, phagocytosis, and migration in response to RGD functionalized surfaces and changes in stiffness of gellan gum hydrogels.

Improving selective targeting to cancer-associated fibroblasts by modifying liposomes with arginine based materials.

A library of arginine-like surface modifiers was tested to improve the targetability of DOPE:DOPC liposomes towards myofibroblasts in a tumour microenvironment. Liposomes were characterised using zeta potential and dynamic light scattering. Cell viability remained unchanged for all liposomes.

The Influence of Polysaccharides-Based Material on Macrophage Phenotypes.

Macrophage polarization is a key factor in determining the success of implanted tissue engineering scaffolds. Polysaccharides (derived from plants, animals, and microorganisms) are known to modulate macrophage phenotypes by recognizing cell membrane receptors. Numerous studies have developed polysaccharide-based materials into functional biomaterial substrates for tissue regeneration and pharmaceutical application due to their immunostimulatory activities and anti-inflammatory response.

Fibroblasts treated with macrophage conditioned medium results in phenotypic shifts and changes in collagen organization.

In tissue regeneration, the goal is to regenerate tissue similar to what was damaged or missing while preventing fibrotic scarring, which may lead to decreased mechanical strength and dissimilar tissue characteristics compared to native tissue. We believe collagen orientation plays a critical role in wound contraction and scarring and that it is modulated by myofibroblasts. We used macrophage conditioned medium to simulate complex events that can influence the fibroblast phenotype during the wound healing process.

Manipulate intestinal organoids with niobium carbide nanosheets.

Multifunctional two-dimensional nanosheet materials have attracted attention in biomedical fields due to their unique physiochemical and biological properties. Interactions between intestinal stem cells and Engineered Nanomaterials (ENMs) are an essential area in research with the growing diagnosis of gastrointestinal (GI) diseases. One unique type of two-dimensional metal carbide nanomaterial, niobium carbide (Nb C), has shown promising properties for potential applications in this field, such as biocompatibility, stability, and high photothermal conversion efficiency.

Poly-l-arginine modifications alter the organization and secretion of collagen in SKH1-E mice.

Functionalized biomaterials interface with tissue upon implantation. There is a growing need to understand how materials properties influence this interaction so that efficient tissue engineering systems can be developed. In this study, we characterize collagen organization in response to functionalized glass beads implanted in SKH1-E mice.

Vitamin C and B as new biomaterials to alter intestinal stem cells.

Vitamin C (ascorbic acid) and vitamin B (niacin) have been extensively studied since the 20th century. In the area of stem cell biology, vitamin C has shown its direct impact toward homeostasis and epigenetic changes (D'Aniello et al., Stem Cells International, 2017, 1-16).

Degradation and Remodeling of Epitaxially Grown Collagen Fibrils.

Introduction—: The extracellular matrix (ECM) in the tumor microenvironment contains high densities of collagen that are highly aligned, resulting in directional migration called contact guidance that facilitates efficient migration out of the tumor. Cancer cells can remodel the ECM through traction force controlled by myosin contractility or proteolytic activity controlled by matrix metalloproteinase (MMP) activity, leading to either enhanced or diminished contact guidance.

Methods—: Recently, we have leveraged the ability of mica to epitaxially grow aligned collagen fibrils in order to assess contact guidance.

How Cross-Linking Mechanisms of Methacrylated Gellan Gum Hydrogels Alter Macrophage Phenotype.

In tissue engineering scaffolds, macrophages play a critical role in determining the host response to implanted biomaterials. Macrophage phenotype is dynamic throughout the host response, and a balance of phenotypes is essential for timely progression from injury to proper wound healing. Therefore, it is important to predict how materials will modulate the response of macrophages.

Second harmonic generation microscopy of collagen organization in tunable, environmentally responsive alginate hydrogels.

We fabricated photocrosslinked, environmentally responsive alginate hydrogels for tissue engineering applications. Methacrylated alginate (ALGMA) hydrogels were prepared across a variety and combination of ionic and covalent (chain growth, step growth, and mixed mode) crosslinking strategies to obtain a range of compressive moduli from 9.3 ± 0.

Transfer of assembled collagen fibrils to flexible substrates for mechanically tunable contact guidance cues.

Contact guidance or bidirectional migration along aligned fibers modulates many physiological and pathological processes such as wound healing and cancer invasion. Aligned 2D collagen fibrils epitaxially grown on mica substrates replicate many features of contact guidance seen in aligned 3D collagen fiber networks. However, these 2D collagen self-assembled substrates are difficult to image through, do not have known or tunable mechanical properties and cells degrade and mechanically detach collagen fibrils from the surface, leading to an inability to assess contact guidance over long times.

Collagen organization deposited by fibroblasts encapsulated in pH responsive methacrylated alginate hydrogels.

The pH of dermal wounds shifts from neutral during the inflammatory phase to slightly basic in the tissue remodeling phase. Stage specific wound treatment can be developed using environmentally responsive alginate hydrogels. The chemistry of these networks dictates swelling behavior.

Chemically Modified Gellan Gum Hydrogels with Tunable Properties for Use as Tissue Engineering Scaffolds.

Gellan gum is a naturally occurring polymer that can cross-link in the presence of divalent cations to form biocompatible hydrogels. However, physically cross-linked gellan gum hydrogels lose their stability under physiological conditions, thus restricting the applications of these hydrogels in vivo. To improve the mechanical strength of the gels, we incorporated methacrylate into the gellan gum and chemically cross-linked the hydrogel through three polymerization methods: step growth through thiol-ene photoclick chemistry, chain-growth via photopolymerization, and mixed model in which both mechanisms were employed.

Click Chemistry and Material Selection for Fabrication of Hydrogels in Tissue Engineering Applications.

This Review gives a brief introduction to hydrogels formed through click chemistry for applications in tissue engineering. Specifically, we focus on three representative click chemistry mechanisms: Diels-Alder reactions, azide-alkyne cycloaddition, and thiol-ene chemistry. Apart from that, we also discuss photoinitiated chain growth polymerization, which also has fast kinetics.

The effect of polarized light on the organization of collagen secreted by fibroblasts.

Recent studies have demonstrated the beneficial effect of low-power lasers and polarized light on wound healing, inflammation, and the treatment of rheumatologic and neurologic disorders. The overall effect of laser irradiation treatment is still controversial due to the lack of studies on the biochemical mechanisms and the optimal parameters for the incident light that should be chosen for particular applications. Here, we study how NIH/3T3 fibroblasts respond to irradiation with linearly polarized light at different polarization angles.

Supramolecular assemblies of alkane functionalized polyethylene glycol copolymers for drug delivery.

Surfactants are commonly used drug carriers, however, there is a lack of understanding regarding the relationship between drug loading, drug release kinetics, and cell internalization with the physicochemical properties of the drug carriers, preventing rational design. The effects of altering hydrophobic and hydrophilic chain lengths on a poly[poly-(oxyethylene)-oxy-5-hydroxyisophthaloyl] (Ppeg) platform for delivering hydrophobic drugs was examined. The synthesized polymers were characterized by nuclear magnetic resonance spectroscopy (NMR), dynamic light scattering (DLS), and zeta potential.

Physicochemical properties of liposomal modifiers that shift macrophage phenotype.

Liposomes are one of the most widely studied drug carriers due to their relative biocompatibility, lack of immune system stimulation, ability to be cell specific, and serve as a protective drug carrier. Due to several physicochemical properties such as size and charge, liposomes naturally target the phagocytic capabilities of macrophages. In the tumor microenvironment, macrophages strongly influence growth and progression, making them an appealing target for drug delivery.

Investigating the Synergistic Effects of Combined Modified Alginates on Macrophage Phenotype.

Understanding macrophage responses to biomaterials is crucial to the success of implanted medical devices, tissue engineering scaffolds, and drug delivery vehicles. Cellular responses to materials may depend synergistically on multiple surface chemistries, due to the polyvalent nature of cell⁻ligand interactions. Previous work in our lab found that different surface functionalities of chemically modified alginate could sway macrophage phenotype toward either the pro-inflammatory or pro-angiogenic phenotype.

Improving selective targeting to macrophage subpopulations through modifying liposomes with arginine based materials.

The effects of surface modifications on liposomes using a library of arginine derivatives for improved drug delivery were examined. Both unmodified and modified liposomes were tested for their drug delivery properties and propensity for internalization by macrophages. All materials were characterized by dynamic light scattering (DLS) and zeta potential.

Methods for Implant Acceptance and Wound Healing: Material Selection and Implant Location Modulate Macrophage and Fibroblast Phenotypes.

This review focuses on materials and methods used to induce phenotypic changes in macrophages and fibroblasts. Herein, we give a brief overview on how changes in macrophages and fibroblasts phenotypes are critical biomarkers for identification of implant acceptance, wound healing effectiveness, and are also essential for evaluating the regenerative capabilities of some hybrid strategies that involve the combination of natural and synthetic materials. The different types of cells present during the host response have been extensively studied for evaluating the reaction to different materials and there are varied material approaches towards fabrication of biocompatible substrates.

Identifying Factors of Microparticles Modified with Arginine Derivatives That Induce Phenotypic Shifts in Macrophages.

Macrophages are key players in the progression of many diseases, ranging from rheumatoid arthritis to cancer. Drug delivery systems have the potential not only to transport payloads to diseased tissue but also to influence cell behavior. Here, poly(-isopropylacrylamide--acrylic acid) (pNIPAm--AAc) microparticles were modified with 14 different arginine derivatives.

The effect of chemically modified alginates on macrophage phenotype and biomolecule transport.

Macrophage (MΦ) reprogramming has received significant attention in applications such as cancer therapeutics and tissue engineering where the host immune response to biomaterials is crucial in determining the success or failure of an implanted device. Polymeric systems can potentially be used to redirect infiltrating M1 MΦs toward a proangiogenic phenotype. This work exploits the concept of MΦ reprogramming in the engineering of materials for improving the longevity of tissue engineering scaffolds.