NANOPARTICLES EMBEDDED BIOMATERIALS IN WOUND TREATMENT: A REVIEW

R.Pujitha Lakshmi

K.Sivaranjani

INTRODUCTION•In spite of so many medical advancements, wound healing still remains a challenging clinical problem for which efficient wound management is necessary.•Researchers are developing wound dressing materials using biomaterials like collagen, chitosan, fibrin, gelatin.•In order to improve the efficiency of them, they started incorporating medically important NPs.• Since, the skin provides a route of delivery for local and systemic drugs, it is being efficiently used to deliver therapeutic products like medically important NPs for treating skin diseases, antimicrobial activity in wounds and burns, cancer treatment.•Hence, NPs embedded biomaterials can be delivered through the SKIN for an efficient wound healing.

The classic model of wound healing is divided into three or four sequential, yet overlapping phases:

(1) Haemostasis,(2) Inflammation, (3) Proliferation and (4) Remodelling.

•Fibrin is the first scaffold that the skin encounters after an injury.•Fibrin gels formed from purified plasma proteins have properties similar to a blood clot and it is biodegradable.•Since fibrin can bind to numerous proteins, similar to a blood clot, it can be used as an haemostatic glue to stop bleeding, replace sutures and also in wound healing. •Can be injected injected in situ for wound healing applications and it is biodegradable.

FIBRIN

COLLAGEN

•The most abundant animal protein.•Plays a vital role in pre and postoperative surgical procedure. It can form fibers of great tensile strength and stability via cross linking and self aggregation. •Collagen from various sources (porcine, rat, leather wastes, piscine)-wound dressing material.•Biodegradable, biocompatible, non toxic, thermally stable.•Used to cover burn wounds and treat ulcers.•Collagen supports the growth of supporting new tissue by adhering to the walls of the wound and absorbing the wound fluids .

GELATIN•Derivative of collagen.•Biodegradable, biocompatible, has excellent physical, chemical and mechanical properties and commercially available at low cost. •Possesses good elongation and deformation properties which provide easier opening of spaces for cell penetration to a deeper level of scaffold.•Hence it can be used as a biodegradable scaffold as efficient substitute in case skin loss.

ALGINATE

•A naturally occurring anionic and hydrophilic polysaccharide•possesses excellent biocompatibility, biodegradability, mechanical strength, cell affinity, gelling properties, non-antigenicity, chelating ability.•Readily processable in the form of hydrogels, microspheres, sponges, foams and fibers which can be used as wound dressing materials•Enhance wound healing by stimulating monocytes to produce elevated levels of cytokines. •Possess high levels of bioactivity due to endotoxins.•Used to treat large volume exudation.

CHITOSAN•Natural polymer derived from chitin.(major source : crab shell)•Biodegradable, biocompatible, antibacterial and non toxic linear chain of polysaccharides.•Hydrophilic and haemostatic in nature and hence, used as a hydrogel for wound healing applications.•Pure chitosan hydrogel is fragile but when used in combination with other biomaterials or compounds for an improved strength.

SILVER

•Bactericidal agent-Effective against both Gram positive and Gram negative bacteria (High effectiveness against Gram negative)•Silver ions bind to thiol groups and vital enzymes, thereby inhibiting the bacterial growth.•Size (<10nm) and shape play a major role.•Higher conc. of silver can even destroy the test cells.•Triangular shaped NPs have shown better results than spherical or rod shaped NPs.

SILVER NPs EMBEDDED BIOMATERIALS

•Collagen based silver NPs – Spherical shape, positive zeta potential, antibacterial activity (against E.coli and S.aureus), non toxicity against tested cells.[Antibacterial activity is due to the electrostatic interaction between negatively charged membranes of bacteria and positive potential of particles (Silva et al, 2014)] .

•β-Chitin/nanosilver hydrogel proved to be effective against E.coli and S.aureus, had blood clotting ability, good water uptake, stable in PBS buffer. (Kumar et al, 2010)

GOLD NPs

Have properties like biocompatibility, ROS (reactive Oxygen Species) scavenging, promote cell proliferation and can be used in targeted drug delivery.

GOLD NPs EMBEDDED BIOMATERIALS

•The cross linking of collagen with gold NPs which allowed the easy incorporation of biomolecules like growth factors, peptides, cell adhesion molecules by their immobilization at the Gold surface without additional altering of collagen structure.The properties of both collagen and gold NPs demonstrated properties like biocompatibility, antibacterial, biodegradability (Luciano et al, 1999).

•A gelatin-chitosan combination with gold NPs was found to be safe, haemostatic and also did a good work in wound healing (Rezania i al, 1999).

•Polyelectrolyte multilayer coated gold nanorods in combination with collagen can alter the polymerization and mechanical properties of ECM component by elucidating differences in collagen remodeling and cellular phenotype.

The collagen gel constructs served as model tissues in which cells can interact with ECM and the NPs in 3 dimensions (Christopher et al, 2009).

ZINC NPs•Zinc NPs are also widely used in cosmetics , besides playing a major role in cellular and enzymatic activities, wound healing , especially burns.•It possesses antiseptic, antibacterial and anti-inflammatory properties.•A size of <100nm and an appropriate concentration would show no adverse effect.

ZINC NPs EMBEDDED BIOMATERIALS:•Chitosan/Zinc NPs when evaluated in vitro demonstrated some disadvantages such as less flexibility, poor mechanical strength, lack of porosity, and a tendency for dressings to adhere onto the wound surface; less antibacterial activity.

•But there were advantages as well: Provided cooling sensation, enhanced swelling, blood clotting and antibacterial activity against specific microbes (Kumar et al, 2012)

•β-chitin hydrogel/zinc oxide NPs composite bandage was fabricated and evaluated as an alternative to existing bandages. •The resultant bandage exhibited controlled swelling and degradation. . It also had antibacterial activity against both Gram positive and Gram negative bacteria. In vivo evaluation showed that the composite had faster wound healing and higher collagen deposition when compared to control (Lakshmanan et al, 2013).

GRAPHENE OXIDE•Graphene oxide possesses important properties of biomedical use : Antibacterial activity, conc. Dependent toxicity, promotes proliferation of cells, non toxic to test cells, excellent mechanical strength, good thermal and electrical conductivity and excellent biocompatibility. •But, it cannot uptake water after a certain limit, degrades on excess fluid absorption.

GRAPHENE OXIDE EMBEDDED NPs

Graphene oxide incorporated collagen-fibrin biofilm treated wounds faster than collagen and fibrin composite. Based on histopathological, physical and biological results, it proved to be an efficient wound dressing material (Sastry et al, 2014).

TITANIUM DIOXIDE NPsTitanium dioxide NPs have limited biological applications. They have good mechanical properties, antibacterial effect against Gram positive and Gram negative bacteria, proliferation of cell growth, prevents bacterial adhesion, support for bone and stem cell formation, enhancing blood clotting.

TITANIUM DIOXIDE EMBEDDED NPs•Chitosan/titanium dioxide NPs showed powerful antibacterial activity and non toxic towards NIH3T3 and L929 fibroblasts. The tested scaffold showed that the wound closure rate is effective in nanocomposite treated wounds compared with that treated with chitosan, positive control and negative control groups (Archana et al, 2013).•In another similar study, Titanium dioxide NPs were incorporated into

chitosan-pectin because of its properties like biocompatibility, antimicrobial activity, water swellable nature, good healing efficiency and tensile strength (Archana et al, 2013).

CONCLUSION•A study on NPs embedded biomaterials proves that a composite of both biomaterial and nanoparticle had benefits of both individual components.•Graphene oxide NPs are not studied much till date and require more attention.

A composite of Collagen/Graphene oxide along with another biomaterial can be tested and is expected to have good results.

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