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Engineered Nanomaterials for Infection Control and Healing Acute and Chronic Wounds Madasamy Parani, Giriraj Lokhande, Ankur Singh, and Akhilesh K Gaharwar ACS Appl. Mater. Interfaces, Just Accepted Manuscript • DOI: 10.1021/acsami.6b00291 • Publication Date (Web): 04 Apr 2016 Downloaded from http://pubs.acs.org on April 5, 2016
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Engineered Nanomaterials for Infection Control and Healing Acute and Chronic Wounds Madasamy Parani 1,2, Giriraj Lokhande2, Ankur Singh3, Akhilesh K Gaharwar2,4,5,* 1
Genomics Laboratory, Department of Genetic Engineering, SRM University, Chennai, Tamil Nadu- 603 203, India
2
Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843, USA
3
Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY 14853 USA
4
Department of Materials Science and Engineering, Texas A&M University, College Station, TX 77843 USA
5
Center for Remote Health Technologies and Systems, Texas A&M University, College Station, TX 77843, USA
Corresponding author:
[email protected] (MP);
[email protected] (AKG) KEYWORDS: Engineered Nanomaterials, Nanoparticles, Nanocomposites, Wound Healing, Infection Control, Antimicrobial
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ABSTRACT: Nanoengineered biomaterials has dramatically expanded the range of tools used for infection control and to accelerate wound healing. This review thoroughly describes the developments that are shaping this emerging field, and evaluates the potential wound healing applications of recently developed engineered nanomaterials for both acute and chronic wounds. Specifically, we will assess the unique characteristics of engineered nanomaterials that render their applicable for wound healing and infection control. A range of engineered nanomaterials including polymeric-, metallic- and ceramic-based nanomaterials that could be used as therapeutic delivery agents to accelerate regeneration of damaged dermal and epidermal tissues are also detailed. Finally, we will detail the current state of engineered nanomaterial for wound regeneration and will identify promising new research directions in infection control.
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1. INTRODUCTION Wounds affect over 6 million people in the US at an annual cost of $25 billion.1-3 This high health and cost burden underlines the importance of research in this field. Wounds are classified as either acute or chronic. Acute wounds heal within a predictable time period (1 to 12 weeks depending on the nature of the wound); however, accelerated wound healing is desirable for recovery, overall health, and cost.4 Chronic wounds do not heal in a predicted time period, are more susceptible to infection, and are considerably more difficult to manage.5 Chronic wounds include pressure ulcers, diabetic ulcers, and vascular ulcers (including venous and arterial ulcers). Age, peripheral neuropathy, peripheral arterial diseases, immunocompromised status, and venous insufficiency are some of the risk factors of chronic wounds. In addition, diabetes is also one of the major risk indicators for chronic wounds, and lifetime risk of developing a foot ulcer in a diabetes patient is estimated to be 25%.6 The most dreaded consequence of unhealed diabetic foot ulcer is limb amputation due to infection, which occurs in 2.1 to 13.7 per 1000 diabetic patients;6 this incidence increases to as high as 80% mortality at five years post-amputation according to long-term studies.7 Therefore, there are multi-faceted research efforts to develop improved clinically-relevant therapeutic approaches aimed at both infection control and achieving faster healing of acute and chronic wounds. The ability of a range of biomaterials to accelerate wound healing and to control infection has been proposed and tested.8-9 Both synthetic and natural polymers could act as therapeutic agents to accelerate regeneration of damaged dermal and epidermal tissues. Most of these polymeric biomaterials are able to mimic some of the physical and biological characteristics of native tissues due to high water content, biocompatibility, and biodegradable nature. Natural polymers investigated for wound healing applications include polysaccharides (chitosan, chitin, dextran,
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alginates, chondroitin, and heparin), proteoglycans, and proteins (collagen, gelatin, fibrin, silk fibroin, and keratin).10-14 A range of synthetic polymers are also investigated for their ability to facilitate re-epithelialization. Some of the synthetic polymers investigated for wound healing includes poly(glycolic acid)(PGA), poly-D, L-lactide-co-glycolide (PLGA), poly(vinyl alcohol)(PVA), poly(lactic acid)(PLA), poly(acrylic acid)(PAA), poly(ɛ-caprolactone) (PCL), poly(ethylene glycol)(PEG), and poly(vinyl pyrrolidone)(PVP). However, most these polymers lack bioactivity and the ability to accelerate the wound healing process; thus, several nanomaterials are incorporated within the polymeric network. Engineered nanomaterials are used to obtain sustain and control release of therapeutics to accelerates the healing process and provides bioactive characteristics. A range of engineered nanomaterials are investigated for biomedical applications including tissue engineering, stem cell therapeutics, biosensing, immunomodulation and drug/gene delivery due to their unique physical, chemical and biological characteristics.15-21 By combining engineered nanomaterials with synthetic or natural polymers, nanocomposite biomaterials with desired characteristic can be designed.22-26 Recently, engineered nanomaterials have found more acceptance in wound healing applications as evident by the increase in publications (Fig. 1). A range of polymeric, metallic and ceramic nanomaterials are investigated for wound healing applications.27-29 Some of the most common nanostructures include nanoparticles, nanofibers, nanocomposite, nanoengineered hydrogels and self-assembled nanostructures.30 These newly developed nanomaterials are extensively used as tissue adhesive, hemostats, antimicrobial agents, and drug/therapeutics/cell delivery agents. Most nanomaterials are used for topical administration to minimize the perceived risks associated with internal use. For example, topically applied antimicrobials are more effective
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than systemically administrated antimicrobials in reducing the infections in granulating wounds.31 Additionally, exposure of nanoparticles in external wounds is more localized and thereby highly controlled.32 Undesirable effects, if any, can be easily detected and controlled due to the accessibility of the target area. The external nature of the whole system permit applied treatments to focus on both faster wound closure and more aesthetic remodeling. Recently, development of effective antimicrobial wound dressings that utilize silver nanoparticles triggered expanded research on the use of nanoparticles and their composites for enhanced wound healing.32-35 While the impact of said nanoparticles will enable faster healing of acute accidental and surgical wounds,36-37 the true benefits of nanomaterials are seen in the dramatically improved healing times in cases of recalcitrant chronic wounds. The healing potential of nanoparticles combined with robust and flexible polymer systems will lead to ideal nanocomposite systems for wound healing and tissue regeneration.38-40 In this review, we will focus on a range of engineered nanomaterials (size
