Asian Journal of Modern and Ayurvedic Medical Science

Research Paper

NEWER ASPECTS OF WOUND HEALING IN SURGICAL SPECIALITIES

Author: Nischal Gupta, Pallav Agarwal, M.K. Agarwal

(1) Dr. Nischal Gupta M.B.B.S., M.S. Service senior resident Department of E.N.T. Institute of Medical Sciences Banaras Hindu University Varanasi (2) Dr. Pallav Agarwal M.B.B.S.

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Successful wound care involves optimising patient’s local & systemic conditions along with an ideal wound healing environment.                                                                                                                             ► Our goal is to find the most appropriate modality or combination of modalities to optimise healing which is given below.

Intermittent pneumatic compression (IPC): -

                               IPC is effective for managing chronic venous ulcers with severe oedema, that are resistant to simple compression therapy (Emoch et al, 200 ba) .A compression pressure of 20-120 mmhg is provided at present intervals to improve venous & lymphatic flow. It is generally used 2 hrs a day for up to 6 weeks. This method is ideal for patients with limited mobility and should be used as an additional therapy to simple compression, not as a substitute (Enoch et al, 200 ba).

Nanocrystalline Silver dressings: -

                           Use of silver in newer form of delivery system as Nanocrystalline silver dressings is one of the latest technologies in the reason of antimicrobial ̊̊ prophylaxis. Elemental silver requires ionization for antimicrobial efficacy. The highly reactive charged silver ion (Ag++) reacts by binding to negatively charged particles such as proteins, DNA, RNA & chloride ions.

             Nanocrystalline silver dressings currently in use contain 2 layers of high density polyethylene net, sandwiching a layer of rayon/polyester gauge. The outer layer is coated with a Nanocrystalline (<20 mm), noncharged form of silver (Ag ̊ ), and the inner layer helps maintain a moist environment for wound healing, because the noncharged silver is less reactive with negatively particle in the wound , it is deactivated much more slowely and provides an initial large bolus of silver followed by a sustained release into the wound. Silver has a very broad spectrum of microbial coverage, including yeast, fungi, mould and even antibiotic resistant bacteria, such as methicillin resistant staphaureus (MRSA) and vancomycin resistant enterococci (VRE). When used at appropriate concentration. Silver is a bactericidal material that kills on contact by inhibiting the respiratory chain at the cytochrome level, as well as interfering with electron transport, denaturing nucleic acids, inhibiting DNA replication and altering cell membrane permeability. Bacterial resistance to silver is exceedingly low.

Topical negative pressure therapy (TNPT) :-

                   Acute wounds are now more frequently treated with TNPT. In patients with significant co-morbidities or other serious injuries, TNPT can be used in large soft tissue injuries, contaminated wounds & wound with compromised tissue. One discovery that the overall volume & dimensions of the wound tend to decrease with TNPT is possibly allowing a less complex reconstruction than would initially be required. TNPT improves local dermal perfusion, promotes angiogenesis , stimulates granulation tissue, decrease interstitial fluid , control wound exudates and bacterial load (Enoch et al, 200 ba) and thus clinically  translated into faster healing rates of wound.

Hyperbaric oxygen:-

                                  Hyperbaric oxygen is a treatment modality used as an adjunct in management of nonhealing wounds. It involves placing the patient in a sealed chamber where 100% oxygen is pressurized to between 1.5 and 3 atmospheres absolute (Ata) for 60-120 minutes over a course of multiple treatments. Hyperbaric oxygen , increases arterial oxygen pressure (PaO₂) which causes vasoconstriction and thus reduces capillary pressure which reduces oedema; as well as causes an increase in hyper oxygenated plasma to the tissue, thus hastens tissue repair process such as collagen elongation and deposition and bacterial killing by macrophages, that are dependent on oxygen. Neovascularisation in wound is enhanced by hyperbaric oxygen as it is shown to stimulate EPCs (Endothelial progenital cells) and stem cell release from bone marrow both by increases cell proliferation within the marrow, as well as by rapid metabolism via matrix metalloprotease mechanisms.

ADVANCED DRESSINGS:-

                              New wound understanding and technology have produced advanced product that help the body to achieve ideal moist, warm, protected wound healing environment. These products range from occlusive films such as Tegaderm, which are permeable to air and water vapour but impermeable to fluid micro organisms, to hydrocolloids such as DuoDERM which are also occlusive but provide absorption of exudates in addition to maintaining a moist environment for autolysis. For heavily exudative wounds, there are a range of absorptive product including various hydrophilic foam dressings, hydrogels, hydro fibres and alginates.

TISSUE ENGINEERED SKIN SUBSTITUTES :-

                              The advances in technology of biomaterials and tissue engineering has resulted in changed with regard to temporary and permanent coverage of wounds especially burn wounds. Autograft is currently the preferred option but many times there is an insufficient amount of tissue available for grafting. Allograft and xenograft can provides a temporary coverage option but; there are problems regarding rejection, possible disease transfer (Prion related), availability and cultured and ethical considerations. Bioengineered skin substitutes, both biosynthetic skin substitute and cultured autologous engineered skins are available to provide temporary and permanent coverage with advantage of availability in large quantities and negligible risk of immunologic issues. Biobrane, Transcyte, Dermograft, apligraf, Integra, Epicel, alloderm are some of these products.

GROWTH FACTORS AND BIOLOGIC WOUND PRODUCTS:-

                               Chronic wounds may be arrested in any of the four phages; commonly however this arrest occasions the inflammatory or the proliferative phases. Normal wound healing is dependent upon numerous cellular mediators, including eicosanoids, cytokines and various growth factors. Use of these biologic products and growth factors produced by recombinant DNA technology can modify the healing process and aims to accelerate it by augmenting or modulating the inflammatory mediators.

EICOSANOIDS are arachidonic acid metabolites including prostaglandins, Prostacyclins, thromboxane and leukotrienes. They primarily affect the early stages of wound healing.            CYTOKINES regulate inflammation by influencing hematopoietic cells and include chemokines, lymphokines, monokines, interleukins, colony stimulating factors and interferon’s.                GROWTH FACTORS have been studied more than any other biologic wound supplement. They are divided into five super families, the most known being the platelets derived growth factors. Recombinant PDGF, (rh PDGF) which is now known as becaplermin (trade name- regranex) is the only current. FDA- approved product in growth factor family.

Products targeting at different phases of wound healing:-

● Products targeting inflammatory phases: -                                                                                     The production and activity of several proteases e.g. Metalloproteases, serine proteases and Neutrophils elastases, may be altered in chronic wounds. Raised level of such proteases can be detrimental to healing and products aimed at counteracting their effect have been developed.                                                                                                                            Promogen; - designed to inactivate proteases and also protect the host’s naturally produced growth factor i it may be useful in treatment of chronic wounds refractory to conventional treatments.

●Products targeting proliferative phase: -                                                                                                               Growth factors, including granulocyte colony stimulating factor (G-CSF) and Transformin growth factor-β (TGF-β) have also been used to target this phase of healing.                                                      -Recombinant human G-CSF, injected subcutaneously has been shown to enhance healing in infected diabetic foot ulcers.                                                                                                                                    -TGF-β₂topical application has been shown to be effective in the healing of diabetic foot ulcers.                                                                                                                                                   -Recombinant PDGF (Becaplermin) is being used topically in chronic diabetic foot ulcer.                                         -Fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) are active in this phase of repair.

 ●Product targeting epithelialisation and remodelling:-                                                                                     -Recombinant human KGF-2 induces proliferation of epithelial cells and has been shown to enhance healing of venous leg ulcers.                                                                                                                     -Topical recombinant human GM-CSF is effective in the healing of venous leg ulcers.                         -TGF-β₃ causes reduced deposition of collagen during the proliferative and remodelling phases, thus reducing scar formation .trails into the efficacy of TGF-β₃ in the treatment of hypertrophic scars are under way; the role of TGF-β₃ in the treatment of keloid scars is unclear.      

                      FUTURE ADVANCES & RESEARCH POTENTIAL:-

Recently the combination of stem cell and gene therapy has emerged as a promising approach for treatment of chronic and acute wounds.

STEM CELL THERAPY:-

                Currentareas of research include use of adult pluripotent stem cells, which have capability to renew themselves and to differentiate into various types of specialised cells such as fibroblasts, endothelial cells and Keratinocytes essential for wound healing. It is thought that the epidermis and dermis are reconstituted by mitotically active stem cells that reside at the apex of rete ridges ( basal stem cell) , the bulge of hair follicles (hair follicular stem cells), and the papillary dermis ( dermal stem cells). Recent reports however, have indicated that bone marrow might also contain early stem cells that can differentiate into other organ tissue such as skin and thus play a major role in wound healing .Thus a variety of sources such as bone marrow, peripheral blood, umbilical cord blood, adipose tissue , skin and hair follicles have been utilised to isolate stem cells to accelerate the healing response of acute and chronic wounds. Recent studies have looked at the potential of skeletal muscle and adipose derived stem cells. Since fat can be obtained relatively easily in most people, adipose derived stem cells have become the ideal large scale source in practical regenerative medicine. They have an advantage over other stem cell sources as they have neither ethical nor immunoreactive consideration as long as they are of autologous origin. Adipose derived stem cells have found to accelerate wound healing and exhibit antioxidant effects under various experimental conditions.

GENE THERAPY:-       

             Gene therapy initially developed for treatment of congenital defects, is a new option for enhancing wound repair. In gene therapy, specific genes encoding for a particular product (e.g. growth factors, cytokines, receptors, adhesions molecules and inhibitors of proteases) are delivered to the target cell (s) to enhance, amend or negate the biological function of the cell (s) and its inherent genetic coding. Genes once incorporated in the cell; affect the cell and its environment by changing the way their products are expressed. The majority of gene delivering systems are based on viral transfection, naked DNA application, high pressure microinjection or liposomal vectors (cationic liposomes). Genes may be employed to augment an affect (e.g. promote healing) such as genes for growth factors and its receptors, or to inhibit an affect (e.g. suppress excessive scaring) such as genes for antibodies against specific growth factors.

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