Use of Oxidized Regenerated Cellulose (ORC)/Collagen/Silver-ORC Dressings Alone or Subsequent to Advanced Wound Therapies in Complex Wounds

Introduction. Chronic or senescent wounds are difficult to heal and often require a multimodal treatment plan. Negative pressure wound therapy (NPWT) or advanced wound dressings, such as oxidized regenerated cellulose (ORC)/collagen/silver-ORC dressings, can be used to promote granulation tissue development and stimulate wound healing in these complex wounds. Objective. This article examines the use of ORC/collagen/silver-ORC dressings alone or subsequent to advanced wound therapies in a retrospective cohort of 24 patients. Materials and Methods. Wounds were assessed upon presentation. If necessary, oral and/or intravenous antibiotics were administered. Each wound underwent sharp debridement. Patients received either ORC/collagen/silver-ORC dressings with a secondary dressing alone or following NPWT. Skin substitutes and epidermal grafting also were utilized to promote wound healing and wound size reduction. Results. Twenty-four patients with an average age of 66.8 ± 12.7 years were treated. The most prevalent comorbidities were hypertension, diabetes, obesity, peripheral neuropathy, hyperlipidemia, coronary heart disease, and tobacco use. Wound types (N = 27) included diabetic foot ulcers, surgical wounds, traumatic wounds, an ulcer (secondary to chronic gout with tophi), and thermal burns. All 27 wounds fully closed, with an average time to heal of 65.5 ± 41.5 days. Conclusions. Use of advanced treatment modalities including NPWT, epidermal grafting, and ORC/collagen/silver-ORC dressings contributed to wound healing in these patients with complex and/or chronic wounds. 

Patients in a wound care center typically have been referred for treatment of chronic wounds present for months and/or years. In many circumstances, these patients have multiple comorbid medical problems that can impair or delay wound healing, contributing to the development of senescent wounds.

Chronic or senescent wounds are difficult to heal and often require a multimodal treatment plan.^1,2 Wound bed preparation through debridement (if possible) and promotion of granulation tissue are necessary to encourage wound closure in these complex wounds.^3-5 Negative pressure wound therapy (NPWT) or advanced wound dressings, such as oxidized regenerated cellulose (ORC)/collagen/silver-ORC dressings, can be used to promote the development of granulation tissue in the wound bed.^6-9 In wounds requiring further treatment, the use of skin substitutes or epidermal grafting may be necessary to promote reepithelialization, especially in large chronic wounds.^10-13

The use of ORC/collagen/silver-ORC dressings alone or subsequent to advanced wound therapies was examined in a retrospective cohort of 24 patients presenting for treatment at a wound care center. 

Wounds were assessed upon presentation. If necessary, oral and/or intravenous antibiotics were administered. Each wound underwent sharp debridement prior to application of advanced wound therapies. Patients received either ORC/collagen/silver-ORC dressings (PROMOGRAN PRISMA Matrix; Systagenix Wound Management Ltd, Gargrave, UK) with a secondary dressing alone or following NPWT (V.A.C. Therapy; KCI, San Antonio, TX). One wound received topical phenytoin and lidocaine for promotion of wound bed granulation, which is an atypical use with limited evidence reported in the literature.^14-16 Offloading (walking boot, total contact cast, surgical shoe, knee rest walker, or wheelchair) was utilized in all patients. In a subset of patients, application of skin substitutes and/or epidermal grafts also were used to promote reepithelialization.

Application of ORC/collagen/silver-ORC dressings

The ORC/collagen/silver-ORC dressings were applied directly to the wound bed. In the case of a non-exudating or low-exudating wound, the dressings were hydrated with a sterile saline solution prior to application. Dressings were reapplied every 2 to 3 days, depending on the amount of wound exudate, because highly exudating wounds required reapplication sooner than wounds with minimal to moderate exudate levels. As the ORC/collagen/silver-ORC dressings are biodegradable and naturally absorbed into the body over time, residual amounts of the dressings were left undisturbed in the wound bed. 

Following the application of the ORC/collagen/silver-ORC dressing, a secondary dressing was applied to help maintain a moist wound environment. A semi-occlusive hydropolymer dressing (TIELLE Hydropolymer Dressing; Systagenix Wound Management Ltd) was applied over the ORC/collagen/silver-ORC dressings to maintain a 1-cm wound edge overlap. Dressing changes occurred every 2 to 3 days.

Application of NPWT

A nonadherent contact layer (ADAPTIC TOUCH Non-Adhering Silicone Dressing; KCI) was placed over exposed structures prior to application of NPWT, as needed. The reticulated open cell foam dressing (V.A.C. GRANUFOAM Dressing; KCI) was cut to fit the wound bed area. The dressing was placed into the wound bed and covered with an adhesive drape, as per the manufacturer’s instructions. Application of continuous negative pressure (-125 mm Hg) by the NPWT system was initiated. Dressing changes occurred every 2 to 3 days.

Epidermal grafting

In 12 patients, epidermal grafting was utilized. A commercially available epidermal harvesting system (CELLUTOME Epidermal Harvesting System; KCI) was used to isolate and harvest the epidermal skin grafts. The donor site area was prepared with a 70% isopropyl alcohol wash and air dried. The harvester was placed over the donor site and secured so complete contact was made with the skin. The vacuum head was attached to the harvester, and warmth and negative pressure were applied to raise the epidermal micrografts (~30–45 minutes). Once the epidermal micrografts had developed, the system unit’s power was turned off using the user interface panel, and the vacuum head was unlatched and removed from the control unit. A nonadherent silicone dressing was placed over the epidermal micrografts and harvested. The micrografts were applied to the wound, and the nonadherent silicone dressing was bolstered with adhesive strips (Steri-Strips; 3M, St Paul, MN). A secondary dressing consisting of 4 x 4 gauze, roll gauze, and tape was applied. The nonadherent dressing remained in place for 7 days following graft transfer. The bolster and donor site dressings were changed once weekly, as per the manufacturer’s instructions. The epidermal harvesting system was removed from the donor site, and the donor site was covered with a transparent film dressing (Tegaderm Transparent Film Dressing; 3M). 

Allogenic skin substitute

The allogenic skin substitute (TheraSkin; Solsys Medical, Newport News, VA) was prepared for application by thawing it in sterile saline under sterile conditions. Once thawed, the skin substitute was unfolded and the mesh removed. Using aseptic techniques, the dermis side of the skin substitute was applied to the wound bed. The excess skin substitute was trimmed to leave a 5-mm to 10-mm edge around the wound and secured in place using adhesive strips, 4 x 4 gauze, roll gauze, and tape.

Twenty-four patients with an average age of 66.8 ± 12.7 years were treated. The most prevalent comorbidities were hypertension, diabetes, obesity, peripheral neuropathy, hyperlipidemia, coronary heart disease, and tobacco use (Table 1). 

In this patient group, there were 27 wounds. Wound types included diabetic foot ulcers (DFUs), surgical wounds, a traumatic wound, an ulcer (secondary to chronic gout with tophi), and thermal burns (Table 2). The average wound age was 70.4 ± 61.6 days. Patients who only received ORC/collagen/silver-ORC dressings had an average wound age of 33.3 ± 33.6 days. In all patients, previous treatments included sharp debridement, antibiotic ointments, and/or NPWT. Wounds were treated with either ORC/collagen/silver-ORC dressings alone or subsequent to NPWT, skin substitutes, or epidermal grafting. All 27 wounds fully closed, with an average time to heal of 65.5 ± 41.5 days. For wounds that only received ORC/collagen/silver-ORC dressings, the average time to heal was 31.5 ± 19.4 days. Of the 24 patients, 3 were treated following recommendations for limb/toe amputation by a previous clinician due to prior treatment failure. In these patients, the ORC/collagen/silver-ORC dressings alone or subsequent to NPWT treatment plan promoted wound closure and contributed to limb/toe salvage in these patients.

Example cases

Case 1. A 49-year-old woman presented with thermal burns on the plantar surface of both feet (Figure 1A) with a duration of 18 days. Previous medical history included diabetes, coronary heart disease, poor nutritional status, obesity, hypertension, acute renal failure, fatty liver disease, myocardial infarction, diabetic peripheral neuropathy, tobacco use, and liver cirrhosis. Previous treatment included over-the-counter antibiotic ointment and oral antibiotics. The wounds underwent sharp debridement, followed by application of ORC/collagen/silver-ORC dressings and offloading via wheelchair use. Wound reepithelialization was observed after 28 days of ORC/collagen/silver-ORC dressing use (Figure 1B), and the wounds completely closed after 63 days (Figure 1C).  

Case 2. An 87-year-old man presented with 3 traumatic wounds of the left foot (proximal medial, distal medial, and dorsal wounds; Figure 2). Initial treatment included debridement, wet-to-dry dressings, oral antibiotics, and offloading by an orthopedist prior to referral to the wound care clinic for care. The ORC/collagen/silver-ORC dressings were applied to the dorsal wound. The dorsal wound fully closed 49 days after presentation (Figure 3). The distal medial wound underwent 14 days of enzymatic debridement using a collagenase ointment. After 14 days, enzymatic debridement was discontinued and use of ORC/collagen/silver-ORC dressings was initiated. The distal medial wound fully closed 70 days after presentation (Figure 4).

The proximal medial wound underwent 14 days of enzymatic debridement using a collagenase ointment, followed by 49 days of topical phenytoin and lidocaine for wound bed preparation. The ORC/collagen/silver-ORC dressings were then applied. After 35 days, about 50% reepithelialization was observed (Figure 5A), and the wound was approved for epidermal grafting (Figure 5B). At 91 days following presentation, the proximal medial wound fully reepithelialized (Figure 5C).  

Case 3. A 44-year-old man presented with nonhealing transmetatarsal amputation dehiscence (4.5 cm x 7.0 cm x 0.3 cm), which was present for 91 days (Figure 6A). Previous medical history included diabetes, poor nutritional status, hypertension, end-stage renal disease, and peripheral neuropathy. Wound assessment revealed adequate blood supply to the wound. Previous treatment included wet-to-dry dressings. The wound underwent sharp debridement (Figure 6B), followed by application of ORC/collagen/silver-ORC dressings, gauze secondary dressings, and offloading utilizing a controlled ankle movement walking boot (Figure 6C). After 35 days of treatment, allogenic skin substitutes were applied (Figure 6D). The wound was approved for epidermal grafting after 42 days and underwent 5 applications of allogeneic skin substitutes (Figure 6E). The wound fully closed 14 days after the epidermal grafting procedure (Figure 6F). Following wound closure, the patient qualified for and was placed on the kidney transplant list.

Chronic or senescent wounds are extremely difficult to heal and often require a multimodal treatment plan. The use of ORC/collagen/silver-ORC dressings alone or subsequent to advanced wound therapies was examined in this report. Following treatment, all wounds fully closed with successful limb/toe salvage in 3 patients. 

With numerous wound care options available, it can be difficult to identify the optimal treatment plan for each patient. Initially, both the patient and wound should undergo a thorough evaluation to identify potential barriers to wound healing.^1-3 Steps can be taken to minimize barriers to healing through the management of comorbidities (eg, improving nutrition, lowering blood glucose, and smoking cessation). For wounds present more than 3 months and have failed treatment, despite removal of wound healing barriers, a biopsy should be done to exclude other causes (eg, carcinoma, inflammatory disorder).¹⁷ Once the assessment is completed, the health care provider will have a better idea of the unique challenges contributing to stalled wound healing and allow for selection of a wound care plan tailored to the patient and wound.

Following the assessment, the care focus should switch to wound bed preparation.^3-5,18 Debridement can be essential in wound bed preparation because it can help remove wound barriers to healing.^3,4 Sharp debridement to remove any necrotic and devitalized tissue, slough, clots, tunneling, undermining, epibole, and infected bone is one of the first steps needed to start the wound healing process in chronic wounds. In the present patient cohort, sharp debridement was performed as the first step in the patients’ wound care plans prior to application of advanced wound therapies.

Next, the ORC/collagen/silver-ORC dressings were applied. The ORC/collagen/silver-ORC dressings transform into a soft, conformable, biodegradable gel after they come into contact with wound exudate. This feature allows the dressing to come in contact with all areas of the wound, as well as maintaining a physiologically moist microenvironment at the wound surface, which may help promote epithelialization, granulation tissue development, and optimal wound healing.^19,20 The individual dressing components can help provide an antimicrobial barrier (ionic bound silver),²¹ reduce surface bleeding (ORC),²² and promote a physiologically moist microenvironment at the wound surface (ORC/collagen).^19,20 However, the effects of ORC/collagen/silver-ORC dressings on granulation tissue formation at the cellular level are not fully understood, and more research is necessary. 

The ORC/collagen/silver-ORC dressings were chosen to aid in wound bed preparation and, in the author’s opinion, were critical to successful wound healing. The components of the dressing have been reported to promote a moist wound environment (ORC/collagen component)²³ and reduce bioburden within the silver-ORC component.²¹ Several randomized controlled trials have reported increased rates of wound healing, wound reduction, and reduced time to heal in complex wounds and patients with multiple comorbidities.^8,9,24 The application of ORC/collagen/silver-ORC dressings acted as the first line of care following debridement in this patient cohort. In 37% (10/27) of the wounds in this study, application of ORC/collagen/silver-ORC dressings and subsequent offloading was sufficient to promote wound healing and closure. These wounds were more recent than those requiring other treatment modalities. However, wound size reduction and development of healthy granulation tissue also was observed in the wounds that needed further treatment. 

Continued reassessment of wound healing is required, allowing for immediate adjustments to the treatment plan when healing stalls.¹ Advanced wound care techniques should be considered if the wound has healthy granulation tissue but not decreased by at least 50% in 4 weeks.²⁵ In this study population, a decision about utilizing other advanced wound dressings or advanced wound care techniques (eg, allografts, skin substitutes, cellular- and/or tissue-based products, or biologics) was made once the wound demonstrated healthy granulation tissue. In practice, the author prefers to use skin substitutes followed by epidermal skin grafts to aid in wound closure. Allograft skin substitutes can help jump-start the wound healing process, due to their growth factors, cytokines, collagen, and cellular mediators that promote wound healing.²⁶ Also, skin substitutes can be applied in the wound care center or office setting, thus avoiding an additional trip to the operating room, use of anesthesia, and creation of a donor site wound. Skin substitutes were utilized in 9 wounds and helped contribute to wound size reduction. It is important to note that multiple applications of skin substitutes are sometimes needed in chronic or large wounds to help promote wound size reduction. The number of skin substitute applications needed depends on the rate of reepithelialization and wound size. Epidermal grafting should not be performed on wounds larger than 10 cm². For a wound larger than this size, the author prefers to utilize multiple applications of skin substitutes until the wound size has reduced enough (≤ 10 cm²) for epidermal grafting. Epidermal skin grafts also can be applied in the office without the use of anesthesia or an operating room. These grafts utilize only the epidermal skin layer and have been shown to contain proliferative cells with the potential to migrate and multiply to achieve reepithelialization.^27,28 Epidermal grafting was utilized in 12 wounds (44.4%) and contributed to full wound healing in these patients, similar to results seen in previously published literature.^12,13,29,3

The limitations of a retrospective cohort and lack of control cohort are present for this study. This study utilized a retrospective cohort, which has inherent selection bias. In addition, no comparison with a standard of care control group was performed. Further studies are needed to examine potential clinical benefits of this treatment plan in large patient cohorts with a standard of care control group.

All of the complex and/or chronic wounds treated with NPWT, epidermal grafting, and ORC/collagen/silver-ORC dressings in these patients healed without complications. Further study utilizing large patient cohorts with a standard of care control cohort to examine potential clinical and health economic benefits of multimodal treatment plans is needed.

Note: The author would like to thank Julie M. Robertson (KCI, San Antonio, TX) for assistance in manuscript preparation and editing.

Author: Robert J. Klein, DPM, FACFAS, CWS

Affiliations: Collom & Carney Clinical Association, Texarkana, TX; and Prisma Health, Greenville, SC

Correspondence: Robert J. Klein, DPM, FACFAS, CWS, 200 Patewood Drive, Suite C300, Greenville, SC 29615; robklein63@gmail.com 

Disclosure: Dr. Klein is a paid consultant for KCI (San Antonio, TX).