Literature Review

Introduction

In the field of health care, the aspect of wound care is an undeniable action induced or caused by unavoidable events that leads to resulting wounds to all individuals who come into contact with such events. The author (Fidler, 2002), states in reference to statistical matters concerning wound endeavors in the state of the U.S. that 37.6 million individuals are taken to the emergency room yearly due to injuries. The commonality of such results stated by (Fidler, 2002) reveals that 4 out 10 patients suffer wound related incidents and 22 percent are open ended wounds inflicted to the patients in which 7 out 10 patients required medicinal medications. Findings reported by (Fidler, 2002) from the National Center for Health Statistics state in the case of wound care, 29.6 percent required therapeutic treatment. For example, the author (Fidler, 2002) provides an account of 1997 in which children under the age of 5 and elderly residents showed that accidental falls were the leading cause of wound injuries. The notion of such a field that promises no span of pre-preventable protection can only be followed by a governing self-sustaining system to treat the wound injuries. The purpose of the literature review is to 1) highlight the medicinal or revolutionary fields that are approaching the effective solution of treating a variety of wound related incident, 2) The self-applicator in relation to its use to the average person. But also, there are still deficiencies in the efficacy of the design. The issues of the review will focus on four areas used to treat wound incidents such as: wound dressings, antiseptic, hemostatic agents and epidermal cell delivery. The conditions of the review will highlight the advantages and disadvantages stipulated by multiple authors along with identifying the similarities and differences. Defining such parameters, the review will identify areas in which fields have progressed from basic wound dressings to cell regeneration. However, the research in this literature review is going to show that even though there have been advancements and expansion of multiple applications, there is always a chance of unforeseen variables that are unavoidable. Thus showing, the need of improving the efficacy of this mechanical and scientific process.

Wound Dressings

The novelty of wound dressings became apparent for their medicinal purposes during the Mesopotamian era around 2500 BCE. However, as the expenditure of technology grew and the innovation of multiple fields became understood such as engineering, biochemistry and organic chemistry, dressing applications highlighted these medicinal improvements. The authors (C, S, L, & D, 2012) and (Mogosanu & Grumezescu, 2014) illustrate a plethora of categorical dressings under investigation or in production commercially, including: natural polymers, glycolipids, proteoglycans, proteins and peptides, synthetic polymers and skin substitutes. But, in the aspect of standard treatment for superficial wounds, items such as gauzes and semipermeable films are more common to the average investor but not spray-on dressings. The apparent nature of these items provided by the author (C, S, L, & D, 2012), elaborates in the sense both advantages and disadvantages of these exclusive items. In referring to gauzes, the author (C, S, L, & D, 2012), details the advantage as being: cheap, accessible, impregnable and physical debridement. However, in referring to the disadvantage one that still has provided problems since the 5th century BCE is the promiscuity of releasing fibers into the affected area, traumatic removal resulting in pain and further bleeding and lateral bacterial migration. Semipermeable films commonly referred to as Band-Aids where founded during the era of World War II under the direction an employee working for Johnson and Johnson by the name of Earle Dickson. The heighten appeal of their functionality during the war was a direct correlation of their sterilization properties, maintaining a moist environment and minimizing the colonization of bacterial migration stated by (C, S, L, & D, 2012). In regards to medicinal disadvantages of the Band-Aid, a slight risk in non-preventable maceration. However, in the respect of aerosolizing the wound aperture in treatment of superficial wounds, authors (C, S, L, & D, 2012), (Gerlach, et al., 2011) and (Camp, 2014) theorize the surface to wound ratio is greater, provides cosmetic advantages and delivers strong viability results. Spray on formulations noted by (C, S, L, & D, 2012), provide an applicable first aid response and reduces infection. However, though the spray applicator is a growing technology, cons prescribed by the author (C, S, L, & D, 2012) stipulate that possible haemolysing can occur. Therefore, the rational of choosing both growing and control dressings is dependent upon the particular case presented to the user. In which, the judgment of rational and logical understanding must be considered when addressing the health care of the wound site. However, this is the first step towards the advancements in improving the efficacy of the healing process in otherwise severe wounds or burns. The secondary measure of treating the wound is no longer about simply covering the wound but addressing the best way of how to clean the wound beyond the superficial injury using antiseptic agents.

Antiseptic

In the progression of treating minor wounds with conditional prep agents, author (Zinn, Jenkins, Swofford, Harrelson, & McCarter, 2010) provides relative evidence in choosing certain prep agents for conditional treatment. However, authors (Zinn, Jenkins, Swofford, Harrelson, & McCarter, 2010) and (Fidler, 2002) stress that when choosing agents: consideration of the patient allergies and skin conditions are recognized, area of treatment is acceptable for that particular agent, manufacture’s review and guidelines are followed for the uses of that agent and preference of the user or medical examiner are considered when choosing an appropriate prep agent for the onsite condition. In response to choosing a prep agent, authors (Zinn, Jenkins, Swofford, Harrelson, & McCarter, 2010) and (Fidler, 2002) highlight that the functionality is secondary to the prevalence of treating minor wound cases. Coordinated distinctions between authors (Zinn, Jenkins, Swofford, Harrelson, & McCarter, 2010) and (Fidler, 2002) enclose that prep agents must coordinate the following functionality: microorganism cell count is decreased from original status, efficient in addressing a plethora of microorganism cultures, fast response and rebound effect in preventing the re-synthesis or re-growth of microorganism sub-populations. In reference to the prep agents, author (Zinn, Jenkins, Swofford, Harrelson, & McCarter, 2010) provides an itemized list of the agents in regards to advantages and disadvantages they pose to the system layer of the body. In regards to the importance of prep agents, authors (Fidler, 2002) and (Zinn, Jenkins, Swofford, Harrelson, & McCarter, 2010) undergo logical reasoning that prep agents are justified in the matter of treating the affected area by: removing soil deposition or elemental components foreign to the layer of the skin, decreasing cell viability of foreign microorganisms and stalling the rebound and regrowth effect of microorganisms to the lining of the skin. For example, iodine base agents with alcohol as stated by (Zinn, Jenkins, Swofford, Harrelson, & McCarter, 2010) provides proficiency in its reactivity towards gram positive and gram negative bacteria, long duration effect, broad spectrum, and immediate germicidal reaction. However, as illustrated by both authors (Fidler, 2002) and (Zinn, Jenkins, Swofford, Harrelson, & McCarter, 2010) iodine base products with alcohol are considered to be highly flammable due to the catalyst of the alcohol present within the mixture, but can be avoided if precautionary steps are taken. In regards to chlorhexidine gluconate as stated by (Zinn, Jenkins, Swofford, Harrelson, & McCarter, 2010), the agent comes with considerable flaws in the case of a drying effect visible on the skin and adverse effects when applied to the eyes, ears, genitalia and mucous membranes. However, consistency exist between both authors (Fidler, 2002) and (Zinn, Jenkins, Swofford, Harrelson, & McCarter, 2010) in the fact that each of the following agents are FDA approved, but a frame of reference of which is preferred as a general control in treating  wounds in hospital settings is still unclear. In looking at unpredictable variables, antiseptic agents have both positive and negative side effects that are detrimental to the repairing process of the skin, thus leaving the hospitals with an unclear decision of which antiseptic agents to use. In spite of this conundrum, antiseptic agents are still considered essential for wound care. In looking at the entire process of wound management after cleaning the wound, if the case is severe enough, where there is heavy bleeding involved, then a hemostatic agent becomes necessary.

Hemostatic Agents

In the process of cultivating the healing cascade of minor wounds, the temperance of distinctive topical hemostatic agents can be applied to assist in the process of healing wounds. When referencing such agents author (Camp, 2014), breaks down topical agents into five categories: passive, active, flowables, fibrin sealants and adhesives. But, this literature review will only focus on three of the topical agents including passive, active and fibrin sealants. Since they are relevant to the research question that is only looking at a self-spraying application in regards to making wound care more accessible to the average person. The process of treating superficial wounds, authors (Camp, 2014) and (Fidler, 2002) understand from a clinical standpoint that associations dealing with first response to a site of bleeding must first be handled mechanically by inducing pressure, sutures or thermal energy. In which case, the same concept applies when choosing an antiseptic or hemostatic, the right solution for the particularity of the incidence. In reference to three of the five hemostatic agents; passive, active and fibrin sealants provided by the author (Camp, 2014) suggest that commercial applications can be used for cell spraying in treatment of superficial wounds. However, the indicative nature of these three categories, holds a distinctive chemical nature that possess both advantages and disadvantages when applied to the user. Passive agents explained by the author (Camp, 2014) provide certain effects that make it very distinctive to other hemostatic agents. The sense of passive agents is the ability for the conditional area to control minimal bleeding. However noted by the author (Camp, 2014), agents classified under this category can work within two to three minutes, inexpensive, preparation technicalities are small and requirements for storage ascertains no special accommodations. The agent undergoes the ability of activation due to the presence of blood, however in the sense of a pro to the nature of the agent disruption of the clotting cascade is not affected. In essence, passive agents can be constructed in the following composition as stated by (Camp, 2014): porcine gelatin, bovine collagen, oxidized regenerated cellulose, polysaccharide spheres and beeswax. In regards to the composition of these passive agents the author (Camp, 2014) highlights the advantages of these components, but provides also a commonality in risk to the usage of such components such as; prevention of any injection into the wound, risk of granuloma/abscess formation, swelling risk and increase infection risk. The advantages provided by (Camp, 2014) include; two to three minute functionality, no preparation needed and no human/animal source. Active agents implore a sense of continuity in the means of controlling blood flow in the same sense as the other agents, however stated by the author (Camp, 2014) they implore thrombin. The author (Camp, 2014) ties a direct correlation to the full functionality of active agents with that of thrombin. Active agents come within the following three formats: bovine thrombin, pooled human thrombin and recombinant thrombin. Statements stipulated by the author (Camp, 2014) assess that an increase in concentration of thrombin provides a higher yield effect to the process of hemostasis. Reasons behind the statement come from the logistic of biological understanding, assessed by the author (Camp, 2014), active agents are processed with the means of delivering high levels of thrombin. Thrombin in the essence of its inner-workings, converts fibrinogen to a fibrin clot which provides clotting aggregation and thrombus to develop at the site of injury. However, a disadvantage noted by the author (Camp, 2014) states that disruption to the thrombin concentration can be manipulated in the sense of denaturing the full effect of thrombin in the wound. The process of reducing the thrombin concentration thereby its functionality can occur in the following way as stated by (Camp, 2014): hemodiluation, absorptive sponges, wound irrigation and wiping or blotting of the wound. In terms of the application of the active agent to the wound area, the author (Camp, 2014) states that measures of spray applicators or direct application can be used to modulate the release of the active agent. Thereby providing the accessibility of different modes of delivery when confronted with different circumstances. Fibrin sealants, in the essence of hemostatic classification under topical, provide full functionality in the directive parameter stated by (Camp, 2014), in the condition of providing the stoppage of bleeding. The author (Camp, 2014) provides strict defining differences between the advantages and disadvantages of this hemostatic agent in controlling superficial wounds. Advantages, include the conclusive demeanor of the foundational makeup that encompass the inner workings of the agent in providing an accelerated level of fibrin clot due to increases in concentration of both fibrinogen and thrombin. The elevated response to levels in concentration provide the opportune creation of a clot due to accelerated responses of both thrombin and fibrinogen when applied to blood. Consequently, disadvantages stated by (Camp, 2014) reveal that the application of the agent to the patient is not suited to a general user with no foreknowledge of the material, but requires the services of a trained technician. Technicians within this endeavor provide basic strengths in the process of basic lab procedures which are conducted towards the effort of retrieving pooled plasma from the patient to reconstitute the product. The nature of the agent allows the ability of the user stated by (Camp, 2014) to deliver the agent via aerosol spray. The delivery of such a method provides an opportune relief in terms of high spray area ratio, mobile delivery of the agent and user friendly. It is this method of delivering the hemostatic agent that begins to make the agent more accessible, however, the drawback is that the user needs certain training skills to use and administer the delivery system. It is in providing this training that is the unforeseeable element that prevents the research from stating that this delivery system can be introduced within the home. By looking closely at the variation in the epidermal cell delivery there is the potential of creating and or modifying a current mechanical design for the self-spray applicator to make this otherwise complex procedure more user friendly.

Epidermal Cell Delivery

Journal entries provided by recent authors have explained the depth and complex nature of basal keratinocyte cell sprays. However, the indicative means by which cell isolation highlights the full parameters of these working conditions constitute both commonalities and differences. In an article published by (Gravante, et al., 2007), ReCell protocols provided only three steps in the coordination of epidermal release of basal keratinocytes, whereas (Gerlach, et al., 2011) provided seven steps. The author’s written proposal provided by (Gerlach, et al., 2011), suggest that due to the protracted explanation given in cell isolation parameters of basal keratinocytes, seem to follow logistic cell isolation standard procedures including: initial separation of dermis and epidermis by trypsin, mechanical separation of dermis and epidermis, transfer of epidermal into Ringer’s lactate solution, placement into a single cell suspension to isolate basal keratinocytes, sieving the cell suspension, centrifugation, cell counting and cell viability protocol. Whereas (Gravante, et al., 2007), followed the manufactures parameters of ReCell protocol, including only the parameters of intracellular detachment of the epidermis by trypsin, mechanical separation and single cell suspension placed in Ringer’s lactate solution. Inducing discrete differences from the means of the reader’s perspective, in considering if modifications or further additives were withheld due to legal holdings of patent protocols over ReCell design publications. However, in comparison with (Gravante, et al., 2007) and (Schlabe, et al., 2008), authors maintained a strict distinction when explaining cell isolation, medium supplements and cultivation as in the tense of providing only the main points and not the finer details of the overall synthetic scope of the design. In the process of fulfilling cell isolation protocols, a transition step was taken to prepare the cell suspension and place the cultivated medium in a modified cell spray. The author (Gravante, et al., 2007), stipulated that once mechanical separation was finalized, the cell suspension constituting of basal keratinocytes in lactate solution was placed in a 5 mL syringe. The particularities of preparing the cell suspension for cell spraying follow the same ideology as (Gerlach, et al., 2011), in which the cell suspension made of Ringer’s lactate solution containing basal keratinocytes was placed in 2 mL syringes. However, cellular spread rate in terms of skin donor site to treatment surface for (Gerlach, et al., 2011) was 1:20, compared to (Gravante, et al., 2007) an estimated 1:80 cellular spread rate. For example, if the ratio was 1:20 in terms of skin donor to treatment surface, a biopsy area of 1 cm2 can cover 20 cm2 of peripheral damage induced by superficial burns. In contrast to the reported statements provided by (Gerlach, et al., 2011) in the process of cell counting and cell viability before placement into the syringe for cell spraying, the author (Gravante, et al., 2007) provided no accounts of cell growth yield or viability of cells. However, the author (Gerlach, et al., 2011) stipulated that the process of cell isolation included a cell counting yield between 0.5 and 4 x 106 cells/cm2 and viability rate between 97 and 99%. In both studies, authors (Gerlach, et al., 2011) and (Gravante, et al., 2007) provided no tangible  results as to the approximation of how many cells survived aerosol release when transitioning from the spray to the recipient area of treatment. In discussing the parameters of feasibility results when introducing cell spraying of basal keratinocytes to residual second degree burn areas, authors (Gerlach, et al., 2011) and (Gravante, et al., 2007) provided similar distinctions in findings. In the findings provided by (Gerlach, et al., 2011), the author stipulated from a subjective assessment that rapid re-epithelialization, discoloration and an acceptable cosmetic outcome was achieved in six to twelve months. However, a conjecture stated by the author (Gravante, et al., 2007) stated that re-epithelialization and cosmetic appearance was comparable to both grafting and ReCell findings within the same time period. In comparing ratios of initial site donor biopsy, (Gerlach, et al., 2011) and (Gravante, et al., 2007) stressed that in treating residual burns, the optimal approach to treating superficial burns is to obtain a small sample, which will provide a substantial spread rate to the area affected. The spread rate highlighted the efficiency of cell spraying from both authors, that if residual burns encompass a majority of the body, a small donor biopsy can be useful in treating an extensive burn injury. In conclusion, the above mentioned articles agree, that using a spray as the method of delivery is highly efficient however the time of repair and the end result of the healing process is similar to that of skin graphing. In making this similarity to an already established method of repairing the skin of a wound there is a need to further explore and or enhance the efficacy of the self-spray as to become a potential preference to skin graphing.

Conclusion

In conclusion, the issues concerning the literature review highlight the proficiency of their healing aperture of wounds, but also details the disadvantages. The fields discussed provide a sense of continuity from the patient perspective in the sense of medicinal products that have been shown to work and or still under design. The considerations of a growing technological era, has provided such means in which to treat wound related incidents providing newer and innovative ways in which to manipulate systems in making them more accessible to the community. Research and design has led to addressing the problematic incidents and providing sufficient resources to both health care providers and residential individuals. Therefore, though the issues were defined as both pro and con in addressing and treating variations in wound related incidents, the justifiable means of the key issues functionality will prove to resolve and assist in incidents where 4 out of 10 patients suffer from. By utilizing the issues into a systematic way, a self-sustaining device such as a spray applicator can be created to implore an all in one system that can be used within the home, work field or school. Thereby, creating both a product that is user-friendly, inexpensive, accessible and accommodating to the particular circumstance.                 

References

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