Surface of the implantable devices is the root cause of several complications such as infections, implant loosening and chronic inflammation. There is an urgent need for multifunctional coatings that can address these shortcomings simultaneously in a manner similar to the structures of extracellular matrix. Herein, we developed a coating system composed of ECM components and a naturally derived polypeptide. The interactions between the coating components create an environment that enables incorporation of an antimicrobial/angiogenic polypeptide. The film composition is based gelatin and hyaluronic acid modified with aldehyde groups (HA-Ald) that can react with poly (arginine) (PAR) through transient interactions. Nanoplasmon measurements demonstrated a significantly higher loading of PAR in films containing HA-Ald with longer retention of PAR in the structure. The presence of PAR not only provides to the film surface antimicrobial (contact-killing) properties but also increased endothelial cell-cell contacts (PECAM) and VEGFA gene expression and secretion by human vascular endothelial cells. This multifunctional coating can be easily applied to surface of implants where it can enact on several problems simultaneously.
- Klíčová slova
- Antimicrobial coatings, ECM, Implants, Multifunctionality,
- MeSH
- antibakteriální látky farmakologie MeSH
- biokompatibilní potahované materiály farmakologie MeSH
- endoteliální buňky pupečníkové žíly (lidské) účinky léků MeSH
- extracelulární matrix metabolismus MeSH
- kyselina hyaluronová farmakologie MeSH
- lidé MeSH
- peptidy farmakologie MeSH
- polymery farmakologie MeSH
- protézy a implantáty * MeSH
- skot MeSH
- vaskulární endoteliální růstový faktor A metabolismus MeSH
- želatina farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky MeSH
- biokompatibilní potahované materiály MeSH
- kyselina hyaluronová MeSH
- peptidy MeSH
- polyarginine MeSH Prohlížeč
- polymery MeSH
- vaskulární endoteliální růstový faktor A MeSH
- želatina MeSH
Macrophages play a critical role in the initial response to foreign materials in the body. As most biomaterial-based implantable devices would be treated as a foreign body by the immune system, there is a need for systems that can establish a favourable interaction between the implanted biomaterial and the host. Herein, we describe such a system that can be used as an ECM-like microenvironment for macrophage polarization. The hydrogel system was designed to provide a co-crosslinkable microenvironment containing both protein and glycosaminoglycan components, a hydroxyphenyl derivative of gelatine (GTN-HPA) and tyraminated hyaluronic acid (HA-TA). Both polymers can undergo a crosslinking reaction between polymer chains via the same polymerisation initiation system where the polymer network is formed by crosslinks between phenols in GTN-HPA and HA-TA. The mechanical properties and swelling of the hydrogel can be easily controlled as a function of the crosslinking mode and by the ratio of GTN-HPA and HA-TA compounds used. THP-1 monocytes were successfully encapsulated in the gels and cultured for up to 28 days. Cells exhibited higher metabolic activity when encapsulated in softer hydrogels (E ≈ 10 kPa) compared to stiffer (E ≈ 20 kPa) material in which monocytes tended to form large clusters. Encapsulation of monocytes in the material with HA-TA content enhanced the expression of macrophage-related genes. We demonstrated a co-crosslinkable GTN-HPA and HA-TA matrix microenvironment that is suitable for in vitro micro tissue model applications.
- Publikační typ
- časopisecké články MeSH
Delivery of growth factors is an indispensable part of tissue engineering. Here, we describe a detachable membrane-based release system composed of extracellular matrix components that can be attached to hydrogels to achieve directional release of bioactive molecules. This way, the release of cytokines/growth factors can be started at a desired point of tissue maturation or directly in vivo. As a model, we develop thin films of an interpenetrating network of double-cross-linked gelatin and hyaluronic acid derivatives. The use of the auxiliary release system with vascular endothelial growth factor results in extensive sprouting by encapsulated vascular endothelial cells. The presence of the release system with interleukin-4 results in clustering of encapsulated macrophages with a significant decrease in M1 macrophages (proinflammatory). This system can be used in conjunction with three-dimensional structures as an auxiliary system to control artificial tissue maturation and growth.
- Publikační typ
- časopisecké články MeSH
As an Extracellular Matrix (ECM) component, Hyaluronic acid (HA) plays a multi-faceted role in cell migration, proliferation and differentiation at micro level and system level events such as tissue water homeostasis. Among its biological functions, it is known to interact with cytokines and contribute to their retention in ECM microenvironment. In addition to its biological functions, it has advantageous physical properties which result in the industrial endeavors in the synthesis and extraction of HA for variety of applications ranging from medical to cosmetic. Recently, HA and its derivatives have been the focus of active research for applications in biomedical device coatings, drug delivery systems and in the form of scaffolds or cell-laden hydrogels for tissue engineering. A specific reason for the increase in use of HA based structures is their immunomodulatory and regeneration inducing capacities. In this context, this article reviews recent literature on modulation of the implantable biomaterial microenvironment by systems based on HA and its derivatives, particularly hydrogels and microscale coatings that are able to deliver cytokines in order to reduce the adverse immune reactions and promote tissue healing.
- Klíčová slova
- biomedical, coatings, delivery systems, hyaluronic acid, immunomodulation, tissue engineering,
- MeSH
- biokompatibilní materiály aplikace a dávkování MeSH
- hojení ran účinky léků MeSH
- hydrogely aplikace a dávkování MeSH
- imunomodulace účinky léků MeSH
- kyselina hyaluronová aplikace a dávkování MeSH
- lidé MeSH
- regenerativní lékařství metody MeSH
- systémy cílené aplikace léků metody MeSH
- tkáňové inženýrství metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- biokompatibilní materiály MeSH
- hydrogely MeSH
- kyselina hyaluronová MeSH
This study aims to design an optimal polyelectrolyte multilayer film of poly-l-lysine (PLL) and hyaluronic acid (HA) as an anti-inflammatory cytokine release system in order to decrease the implant failure due to any immune reactions. The chemical modification of the HA with aldehyde moieties allows self-cross-linking of the film and an improvement in the mechanical properties of the film. The cross-linking of the film and the release of immunomodulatory cytokine (IL-4) stimulate the differentiation of primary human monocytes seeded on the films into pro-healing macrophages phenotype. This induces the production of anti-inflammatory cytokines (IL1-RA and CCL18) and the decrease of pro-inflammatory cytokines secreted (IL-12, TNF-α, and IL-1β). Moreover, we demonstrate that cross-linking PLL/HA film using HA-aldehyde is already effective by itself to limit inflammatory processes. Finally, this functionalized self-cross-linked PLL/HA-aldehyde films constitutes an innovative and efficient candidate for immunomodulation of any kind of implants of various architecture and properties.
- MeSH
- buněčná adheze účinky léků MeSH
- buněčná diferenciace účinky léků MeSH
- cytokiny aplikace a dávkování chemie MeSH
- imunomodulace účinky léků MeSH
- kultivované buňky MeSH
- kyselina hyaluronová chemie MeSH
- lidé MeSH
- makrofágy cytologie účinky léků metabolismus MeSH
- monocyty cytologie účinky léků metabolismus MeSH
- polyelektrolyty chemie MeSH
- povrchové vlastnosti MeSH
- reagencia zkříženě vázaná chemie MeSH
- zánět farmakoterapie imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cytokiny MeSH
- kyselina hyaluronová MeSH
- polyelektrolyty MeSH
- reagencia zkříženě vázaná MeSH
