Collagen: Its Role in Wound Healing Here’S an Update on the Practice Management of This Treatment
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WOUND MANAGEMENT Collagen: Its Role in Wound Healing Here’s an update on the practice management of this treatment. BY ALEC O. HOCHSTEIN, DPM AND ANIMESH (ANDY) BHATIA, DPM What Is Collagen? healing, proteases such as MMPs, There are a number of different Collagen is the most abundant are attracted to the wound during collagen dressings available that use protein in the human body and is a the inflammatory phase and have a variety of carriers and combining major component of the extracellu- an important role in breaking down agents such as gels, pastes, polymers, lar matrix (ECM). It is comprised of unhealthy ECM so that new tissue and oxidized regenerated cellulose. 103 three polypeptide chains that are rich forms. However, when MMPs are The collagen contained in these prod- in hydroxy-proline amino acids and present in a wound at elevated levels ucts also varies in type and source. are twisted together into a triple-heli- for a prolonged period of time, this Certain dressings contain native (type cal structure. results in the destruction of healthy I) collagen in which the triple helix Over 20 different types of colla- ECM, which is associated with de- formation is intact; others contain gen have been identified in humans; layed wound healing and an increase denatured or reconstituted collagen, the main types are type I, II, and III; in wound size. which is referred to as gelatin. and together they make up 80% of When the excess of MMPs is not Most collagen dressings contain the body’s collagen. Type I and III are important for wound healing. Collagen plays an important role Role of Collagen in Wound Healing in each of these phases of wound healing due to its In a healing wound, a cascade of events occurs and is broken into chemotactic role. what is known as the phases of wound healing. These include plate- let accumulation, inflammation, fi- balanced by normal physiological collagen derived from bovine and broblast proliferation, cell contrac- processes, alternative methods are porcine sources. Although these col- tion, angiogenesis and re-epitheliali- required to reduce protease levels in lagens are purified, there remains zation. This cascade ultimately leads the wound. This suggests a role for a theoretical concern regarding the to scar formation and wound remod- dressings containing collagen in the potential for prion diseases such as eling. management of wounds where heal- bovine spongiform encephalopathy. Collagen plays an important role ing is stalled (Rangaraj, et al., 2011). There have also been concerns re- in each of these phases of wound garding the integration of porcine col- healing due to its chemotactic role. It What are Collagen Dressings? lagens into scar tissue, while cultur- attracts cells such as fibroblasts and Native intact collagen provides a al/religious issues may prevent their keratinocytes to the wound. This en- natural scaffold or substrate for new use on some patients. Human-de- courages debridement, angiogenesis tissue growth. Dressings containing rived collagens are linked with fewer and re-epithelialization. collagen are thought to provide the immunological concerns; however, A chronic wound is stalled at one wound with an alternative collagen they tend to be more expensive than of these healing stages. This usual- source that can be degraded by the animal-derived collagens. ly occurs during the inflammatory high levels of MMPs as a sacrificial phase and is linked to elevated levels substrate, leaving the endogenous Collagens and Wound Healing of matrix metalloproteinases (MMPs) native collagen to continue normal Bringing successful wound care in the wound. In normal wound wound healing. Continued on page 104 www.podiatrym.com AUGUST 2014 | PODIATRY MANAGEMENT WOUND MANAGEMENT Collagen (from page 103) wound healing. Collagens were thus considered “bioac- tive” in having a physiological activity beyond moisture protocols into a podiatric practice requires familiari- management. ty with the available wound products, as well as their Wounds cannot heal without growth factors in the intended and appropriate use depending on the type right places at the right times in the right quantities. of wound presentation the practitioner is presented MMPs also degrade growth factors (e.g., protein chains) with. that regulate cell populations and activity. Inflammation Collagen has been used widely within wound care, and the production of MMPs can be prolonged due to and in multiple forms for different reasons. The mul- failure to completely remove necrosis or debris or by the tiple forms of collagen lend themselves to a variety presence of microorganisms in numbers beyond critical of wound presentations, making it a favorite among colonization. Microorganisms contribute to the MMP mix wound specialists. and stimulate inflammatory mediators and cells, trapping It had become apparent that chronic wounds were the wound in the inflammatory phase of healing. Many trapped in the inflammatory phase of wound healing and discussions focus on the need to reduce bio-burden, and would not progress to healing without resolving inflam- collagen products that contain silver have been intro- mation. During the inflammatory phase, a wound at- duced to this effect. tempts to cleanse itself of all non-viable tissue and debris by utilizing digestive enzymes to break down non-vital Collagen Dressing Types and Uses: tissue and exudate to wash away the debris. Collagen dressings are available in: The major classes of enzymes responsible for di- • Powders gesting non-viable tissue (largely collagen) are the ma- • Amorphous gels/pastes trix metalloproteases (MMPs), including several that • Gel-impregnated dressings digest collagen. The current justification for use of • With and without adhesive borders 104 collagen dressings suggests that they provide a sacri- • Standard-size wound dressing pads ficial substrate that diverts the MMPs from digesting • Ropes for undermining or cavity wound fill newly formed tissue and by tipping the balance towards Collagen is often combined with other substrates to provide additional properties such as gelling (alginate) or the expansion of enzyme removal to elastase (ORC-ox- idized regenerated cellulose). Some products promote native long-chain collagen as superior for scaffolding and activation of growth factors, while others promote dena- tured (partially broken-down) presentations for their abil- ity to provide high numbers of active binding sites that rapidly interact and remove offending MMPs and high levels of amino acids for use in building new collagen structures. Newer classes promote the use of “Activated” or hydrolyzed collagen which are immediately bioactive and are readily taken up by the cellular matrix of the wound. Collagen dressings can be tried for jumpstarting wounds that are stalled in the inflammatory phase, as they may be responsible for reducing inflammation as well as pain (or the results and mediators of inflam- mation). They have been shown to attract and activate fibroblasts (proliferative stage cell population) and may provide an organizing or scaffolding effect. Activated, Native, Processed and Denatured Collagens Native collagen materials present a more natural 3-D structure that may provide a more natural environment for fibroblasts and better targets for MMPs. They also bind better to elastin and may aid in conserving elastin levels. Processed or denatured collagen may provide a more readily available source of amino acids necessary for tis- sue reconstruction and a higher number of exposed active sites to divert MMPs from digesting newly formed tissue. Continued on page 105 AUGUST 2014 | PODIATRY MANAGEMENT www.podiatrym.com WOUND MANAGEMENT Collagen (from page 104) dispensable and reimbursable prod- Current clinical information uct can have significant financial im- which supports the reasonableness Advances in Wound Dressings pact for the dispensing wound care and necessity of the type and quan- Over the last 30 years, there has practice. Podiatrists have been very tity of surgical dressings provided been a shift from traditional wound effective at enhancing outcomes for must be present in the patient’s med- dressings towards those advanced patients by dispensing orthotic de- ical records. Evaluation of a patient’s therapies that aim to optimize the vices, braces, and splints at point of wound(s) must be performed at least wound healing environment (Enoch service. Wound care products can be on a monthly basis unless there is and Harding, 2003). In more recent as significant, if not more so, for our documentation in the medical record years, wound care products have patients and the bottom line. which justifies why an evaluation been developed that aim to replicate Most insurers reimburse DME. could not be done within this time- or add to the ECM. The ECM is the Medicare, which handles these de- frame and what other monitoring major component of the dermis and vices through one of four Durable methods were used to evaluate the provides a structural support for cells, Medical Equipment Regional Carriers patient’s need for dressings. growth factors, and receptors that are (DMERC), requires a separate provid- Evaluation is expected on a more essential to wound healing. The ideal er number in order to submit claims. frequent basis (e.g., weekly) in pa- dressing should achieve rapid healing Information defining the num- tients in a nursing facility or in pa- at reasonable cost with minimal im- ber of surgical/debrided wounds tients with heavily draining, infect- pact on the patient’s daily activity. being treated with a dressing, the ed wounds or those wounds where reason for dressing use (e.g., surgical there have been significant clinical DMERC Reimbursement Model wound, debrided wound, etc.), and changes. The evaluation may be and Documentation Requirements whether the dressing is being used performed by a nurse, physician, or The benefits of using collagen in as a primary or secondary dressing other healthcare professional. This the podiatric office extend beyond or for some non-covered use (e.g., evaluation must include the type of 105 the efficacy it affords patients for wound cleansing) must be included each wound (e.g., surgical wound, their wounds.