Prospective Multicenter Evaluation of an Advanced Extracellular Matrix for Wound Management : Advances in Skin & Wound Care

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Prospective Multicenter Evaluation of an Advanced Extracellular Matrix for Wound Management

Raizman, Rose RN-EC, NSWOC, MSc; Hill, Rosemary RN, CWOCN, CETN(C); Woo, Kevin PhD, RN, NSWOC, WOCC(C), FAPWCA

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Advances in Skin & Wound Care 33(8):p 437-444, August 2020. | DOI: 10.1097/01.ASW.0000667052.74087.d6
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To evaluate an advanced extracellular matrix made of ovine forestomach matrix (OFM) for healing a variety of wound types.


Participants were enrolled from inpatient, outpatient, and home healthcare settings. The OFM was used to treat all wounds and applied to the wound bed every 3 to 7 days until closure.


Researchers enrolled 29 participants with 33 wounds. Average time to wound closure was 8.2 weeks, the percentage of wounds that reduced in size by 50% or more at 4 weeks was 64%, the average wound area reduction at 4 weeks was 66%, and 73% of wounds had closed at 12 weeks. No adverse effects were observed.


This represents the first Canadian evaluation of OFM for the treatment of wounds, and the positive healing outcomes observed could support more widespread adoption of this matrix.


The dermal extracellular matrix (ECM) in soft tissues is a diverse and heterogeneous entity comprising many different proteins and carbohydrates.1 The appreciation of the role of ECM in all aspects of soft tissue repair has evolved dramatically as understanding of its molecular and biologic complexity has advanced. This intricate network not only provides structural support to the skin but also regulates cellular growth, migration, and differentiation—functions that are vital to tissue repair and wound healing.2–4 The field of matrix biology has identified roughly 1,000 different proteins collectively termed the “matrisome” that exist in tissue ECM and play a role in tissue homeostasis and disease.5 Proteins such as collagen types I, III, and IV, as well as adhesion proteins (eg, fibronectin, laminin) and signaling molecules such as fibroblast growth factor 2, transforming growth factor β, and connective tissue growth factor continuously interact with the cells, which in turn instruct and construct the ECM. This process of dynamic reciprocity underscores the complexity of the ECM and thus its central role in tissue maintenance.6

Acute and chronic wounds are characterized by missing or damaged ECM.7 In the case of chronic wounds, elevated tissue proteases contribute to the stalled state of these wounds by continuously degrading the ECM, acting against fibroblasts working to reconstruct the skin’s scaffold.2,8 With advances in modern regenerative medicine, missing or damaged ECM can be replaced or augmented by exogenous sources,9,10 such as purified or partially purified xenogeneic decellularized ECM isolated from an appropriate animal species (eg, porcine, ovine, or bovine) or allogeneic ECM from cadaveric sources.11–13 These new technologies represent a paradigm shift from the traditional reconstituted collagen scaffolds first developed in the 1980s for soft tissue repair and wound management. Reconstituted collagen products, manufactured using a bottom-up approach (also referred to as solution phase processing),14,15 require reformation of the collagen fiber organization to recapitulate the structure found in tissues.16 In contrast, the preparation of decellularized ECM scaffolds proceeds via a top-down, selective removal of cellular components with a focus on retaining the preexisting ECM structure, composition, and complexity.12 In this way, exogenous ECM scaffolds serve as biomimetics of tissue and can faithfully recapitulate ECM biology during the repair process.

One decellularized ECM isolated from ovine forestomach tissue (OFM; Endoform Natural Dermal Template; Aroa Biosurgery, Auckland, New Zealand) is an intact ECM with a composition and structure that closely mimic human soft tissues.17 This OFM has been shown to retain the native collagen architecture of tissue ECM, with an open porous structure to enable rapid cell repopulation.18 It contains a large number of matrisome proteins and includes collagens,19 glycoproteins, signaling molecules, and growth factors.20 In vitro and in vivo studies have shown that this OFM stimulates cellular differentiation, migration, and the rapid development of vasculature.17,21 Just like tissue ECM, OFM supports cell proliferation and over time is fully bioabsorbed into the regenerating soft tissue.21 Further, tissue ECM is an important regulator of the inflammatory response, and the OFM contains components that modulate tissue proteases associated with wound chronicity.22,23 Accordingly, this OFM has been used extensively in the management of acute and chronic wounds and for complex abdominal wall repair.24–31

Like all healthcare systems worldwide, the Canadian system is seeing an increasing number of chronic nonhealing wounds.32,33 Chronic wounds do not follow a predictable or expected healing pathway and may persist for months or years despite best practices. The exact mechanisms that contribute to poor wound healing remain elusive; an intricate interplay of systemic and local factors is likely involved. With an aging population and increased prevalence of chronic diseases, many wounds can be recalcitrant to healing, placing a significant physical, mental, social, and financial burden on the health system as well as individuals living with wounds. Therefore, the aim of this prospective case series was to evaluate the OFM for treatment of acute and chronic wounds across a continuum of Canadian care settings.


Informed consent was obtained from all participants. All procedures were performed in accordance with the ethical standards of the respective institutions involved and the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Eligible patients who received wound care services in 2018 and 2019 from healthcare facilities including inpatient, outpatient, and home health settings were recruited to represent a cross section of wounds typically managed on a routine basis. In this multisite study, each hospital had a site coordinator who enrolled participants and collected the data. The investigators initially approached potential participants with wounds and obtained consent from those who expressed interest to participate.

Only patients older than 18 years were included. Exclusion criteria included any medical condition that could compromise healing. Participants who were unwilling to follow the study protocol or could not provide informed consent were excluded from the study.

Treatment Protocol

Aroa Biosurgery supplied the OFM used in this study. Product indications, contraindications, and precautions were followed (Table 1). Prior to application, the OFM was cut to size as needed and then rehydrated in sterile saline or wound exudate. After OFM application, the wounds were dressed using either a nonadherent petrolatum dressing and gauze bandages, antibacterial foam dressing bound with gentian violet and methylene blue (GV/MB; Hydrofera Blue; Hydrofera LLC, Manchester, Connecticut), negative-pressure wound therapy, or absorbent foam (eg, Mepilex; Mölnlycke Health Care, Norcross, Georgia). Compression stockings and appropriate off-loading strategies (controlled ankle movement walker boot, offloading padding, and total contact cast) were used as needed. In addition to the OFM, all wounds were managed with local best practice, including debridement during the initial consultation and maintenance of a moist wound environment.

Table 1.:

After the initial consultation, the investigators assessed the wounds every 3 to 7 days. At each visit, the investigators would cleanse the wounds and perform debridement as necessary. Next, the investigators took a photograph of each wound, obtained wound measurements using a paper ruler, and documented the type of wound tissue, including evidence of OFM in the wound. The OFM was reapplied if no residual was present in the wound bed; typically, this was twice weekly for the first 3 to 4 weeks and then weekly as wounds resolved. During the evaluation, the investigators also documented their subjective impressions of the dressing performance based on its fluid handling properties, ease of application, and conformity to the wound using a standardized evaluation tool designed for this study.

Participants were discharged from the study when their wounds achieved 100% re-epithelialization and stopped producing drainage.

Data Analysis

Demographics and outcomes data were prospectively recorded on the patients’ medical records and then retrospectively extracted from the electronic medical records and entered into an Excel spreadsheet (Microsoft Inc, Redmond, Washington). Wound surface area (cm2) was calculated by multiplying the longest length (cm) and width (cm) of wound dimensions perpendicular to each other. Percentage reduction in wound area was determined based on the initial wound area. Endpoints measured were the number of healed wounds, average time to wound closure (weeks), and wounds closed at 12 weeks. At 4 weeks, “responder” wounds were defined as those that were 50% or less of the initial wound area. A Kaplan-Meier survival analysis was determined using Excel, and the survival curve used to approximate the number of weeks to achieve closure of 50% of all wounds.


A total of 33 wounds from 29 participants were enrolled in the study. These wounds included venous leg ulcers (VLUs; n = 4, 12%); diabetic foot ulcers (DFUs; n = 8, 24%); pressure injuries (n = 8, 24%); surgical wounds (n = 5, 15%); traumatic wounds (n = 4, 12%); and other wounds (n = 4, 12%), such as pilonidal sinus, necrotizing fasciitis, and radiation-induced injury (Table 2). Fifty-five percent of the participants were male. All wounds were chronic, except one acute surgical wound. During the study, 6 wounds were lost to follow-up, allowing 27 wounds to be followed to closure (Table 2). The average wound duration was 22 weeks (n = 33; range, 0-104 weeks; Figure 1A). The average wound size was 20 cm2 (n = 33), with a range of 0.1 to 165 cm2 (Figure 1B).

Table 2.:
Figure 1.:

According to the evaluation by the investigators, the OFM demonstrated excellent handling properties, allowing easy application and conforming well to the wound beds. For deep undermined or tunneled wounds, the OFM could be packed into the defect following rehydration. The OFM required no special handling or storage and could be applied by all those involved in care. No adverse events were reported during the study.

Primary outcomes are shown in Table 3. During the study, six wounds from six participants were lost to follow-up (four at 4 weeks, one at 7 weeks, and one at 11 weeks). The remaining cohort (n = 27) comprised the wounds followed to closure. In this subgroup, the average time to wound closure was 8.2 weeks (range, 2.7-19.7 weeks). At 4 weeks, the average percentage wound area reduction was 66% (n = 33; range, 4%-100%). The percentage of all wounds judged closed by 12 weeks was 73% (n = 24/33), or 89% (n = 24/27) when excluding those wounds lost to follow-up. A responder analysis was conducted and showed that at 4 weeks of treatment, 64% (n = 21/33) of all wounds had reduced by at least 50% of the original wound area. The percent of responder wounds increased to 78% (n = 21/27), when wounds lost to follow-up were excluded from the analysis. A Kaplan-Meier survival analysis (Figure 2) was used to estimate the time to closure of 50% of all wounds, 7 to 8 weeks.

Table 3.:
Figure 2.:
KAPLAN-MEIER SURVIVAL CURVE ANALYSISAll wounds (dashed line, n = 33) and only wounds that were followed to closure (n = 27, solid line). Time to closure of 50% of wounds (7–8 weeks) was estimated based on the survival curves (red dotted line).


Case Study 1: Surgical Wound

A 54-year-old woman with celiac disease, hypertension, and idiopathic neutropenia underwent previous surgical repair of left knee. The procedure included the removal of the external fixator, open reduction, and internal fixation of the left tibial plateau and shaft, as well as repair of the medial collateral ligament and medial meniscus, resulting in a nonhealing wound. At the time of intervention, the wound was approximately 8 weeks old and had a layer of dry eschar (Figure 3A). The wound had been previously managed with Polysporin (Johnson & Johnson Inc, New Brunswick, New Jersey). The initial full-thickness wound size was 5.8 × 2.0 cm with 10% slough and 90% granulation tissue (Figure 3B).

Figure 3.:
CASE STUDY 1A, Surgical wound at presentation and prior to debridement with layer of eschar covering the wound bed. B, Postsurgical debridement and prior to initiating management with ovine forestomach matrix (OFM). C, Three days after OFM treatment. D, Two weeks after treatment. E, Wound 100% epithelialized at 4 weeks.

Providers conducted a conservative sharp debridement to remove the eschar followed by cadexomer iodine (Iodosorb gel; Smith & Nephew, Watford, United Kingdom) disinfection. The OFM was applied to the wound bed along with a GV/MB foam covering and a light compression sock. Within 2 weeks, the wound size had reduced to 3.8 × 1.7 cm, and 100% granulation tissue was achieved (Figure 3D). After 4 weeks of OFM management, the wound was closed (Figure 3E).

Case Study 2: Pressure Injury

A 55-year-old man with rheumatoid arthritis sustained a right tibial plateau fracture. A pressure injury to the right anterior ankle with exposed tendon was discovered upon removal of the cast. The wound, measuring 2.2 × 1.5 cm, persisted for approximately 4 months and was being managed with standard of care. The OFM treatment was initiated (Figure 4A), was covered with GV/MB foam secondary dressing, and underwent weekly dressing changes and reapplication of OFM. Within 4 weeks, the wound had begun to reduce in size, and granulation tissue had filled the defect and covered the exposed tendon (Figure 4C).

Figure 4.:
CASE STUDY 2Management of a pressure injury with ovine forestomach matrix (OFM). A, Initial presentation of the wound, with exposed tendon. B, Week 2. C, Week 4. By week 4, granulation tissue had covered the exposed tendon and filled the defect.

Case Study 3: Full-Thickness Wound

A 67-year-old woman presented with profound cellulitis on her left leg and foot, resulting in a 6-month blister on the dorsal aspect of foot, which ultimately proceeded to a full-thickness wound (Figure 5A). Previous treatment with a silver barrier dressing (Acticoat; Smith & Nephew) and hydrogel (Intrasite; Smith & Nephew) was unsuccessful. The wound measured 4.6 × 2.7 cm after debridement. The OFM was applied with a GV/MB foam secondary dressing. After 4 weeks, granulation tissue could be observed in the wound bed (Figure 5B), and the patient reported a reduction in pain. The wound continued to reduce in size measuring 4.2 × 2.5 cm, 4.0 × 2.0 cm, 3.0 × 1.8 cm, 2.4 × 1.3 cm, and 2.3 × 1.0 cm on weeks 4 (Figure 5B), 8 (Figure 5C), 10 (Figure 5D), and 11 (Figure 5E), respectively.

Figure 5.:
CASE STUDY 3Management of a full-thickness wound with ovine forestomach matrix. A, Week 0. B, Week 4. C, Week 8. D, Week 10. E, Week 11.

Case Study 4: Diabetic Foot Ulcer

A 62-year-old man with type 2 diabetes presented with a 1.3 × 1.0-cm DFU on the fifth metatarsal head of his right foot. The wound had been unresponsive to treatment for 2 months (Figure 6A). Providers initiated wound management with the OFM (Figure 6B), and the wound reduced to 25% of its initial size by week 4 (Figure 6C, 1.2 × 0.3 cm) and closed at week 5 (Figure 6D).

Figure 6.:
CASE STUDY 4Management of a diabetic foot ulcer with ovine forestomach matrix (OFM). A, Prior to the initiation of OFM management, wound had been unresponsive to standard of care for 8 weeks. B, Week 0 at the initiation of OFM management. C, Week 4. D, Week 5.


Few technologies are available to address the underlying pathology of ECM degradation in chronic wounds, namely, excessive tissue proteases. Although some reconstituted collagen dressings can modulate downstream gelatinases and neutrophil elastase,34,35 the present OFM can modulate not only the gelatinases but also the collagenases (matrix metalloproteinase [MMP]-1, MMP-8, and MMP-13), stromelysins (MMP-3 and MMP-10), macrophage metalloelastase (MMP-12), and membrane type I MMP (MMP-12), as well as neutrophil elastase.22 Recent studies have identified that tissue inhibitors of metalloproteinases are present in OFM,20 which may in part account for its observed modulatory effect, although based on the complexity of tissue ECM, it is highly likely that several modulatory mechanisms are involved. By providing broad-spectrum protease modulation, the OFM works across the enzymatic cascade of collagen degradation rather than simply acting on the downstream gelatinases. Both tissue ECM and OFM modulate wound proteases while concurrently being degraded by wound proteases. As such, the OFM will have a shorter half-life (persistence) in chronic wounds characterized by elevated protease concentrations relative to wounds that have transitioned to the proliferative phase of healing.

During the course of this study, OFM was often observed as a golden gel present in the wound bed, reminiscent of wound slough. This residual proteinaceous material results from the enzymatic digestion of the OFM in the presence of high protease activity. As the underlying inflammation of the chronic wound was addressed, more residual OFM was seen in the wound bed. The presence or absence of residual OFM material in the wound denotes the inflammatory nature of the wound and can guide the required frequency of material reapplication.36

During the proliferative phase of soft tissue healing, exogenous ECMs provide a bioscaffold for cell attachment, migration, and proliferation, leading to the regeneration of the missing or damaged tissue. This OFM can be infiltrated by a variety of cell types and scaffolds tissue repair,21 a process made more efficient by the retention of native tissue ECM structure and composition.20 Clinically, investigators observed the formation of well-vascularized granulation tissue with concomitant advancement of the epithelial tongue as the OFM scaffolded tissue formation.

Although advanced ECM technologies have been available for several years to augment tissue proliferation and wound closure, the in accessibility of these cellular and/or tissue-based products has limited their adoption in Canada and elsewhere. In contrast, OFM is comparatively affordable,24,37 making this type of advanced technology accessible to a wider group of wound care patients for the first time. The availability of OFM has enabled a paradigm shift in deploying these types of advanced ECM technologies whereby wounds can now be treated earlier and in a more aggressive fashion to reduce the long-term costs of chronic wounds.38,39

The closure rates noted in the current study are comparable with other published studies describing the use of OFM for the management of complex wounds. The incidence of closure at 12 weeks was 89% (n = 24/27) when excluding those lost to follow-up; similarly, Bohn and Gass37 observed a 12-week closure incidence of 96% for VLUs (n = 23). Further, Lullove25 and Liden and May24 observed a 59% (n = 53) and 50% (n = 19) 12-week closure incidence, respectively, using OFM to manage a mix of VLUs, DFUs, and PIs. Ferreras et al26 observed a 12-week closure incidence of 73% (n = 109) when the OFM was used in conjunction with cellular and/or tissue-based products.

To put these results into perspective, a review of the US Wound Registry determined the 12-week closure incidence using standard of care for DFUs, PIs, and VLUs as 31% (n = 62,964), 30% (n = 66,577), and 44% (n = 97,420), respectively. Published studies using reconstituted collagen dressings such as Promogran (Acelity, San Antonio, Texas) have observed 12-week closure rates of 37% (n = 138) for DFUs40 and 41% (n = 37) for VLU,41 whereas Schmutz et al42 observed only a 1% closure at 12 weeks (n = 60) for VLUs. The overall proportion of responders in the current study was 64% (n = 21/33); in contrast, Gottrup et al43 observed that 43% of patients responded to treatment with moist gauze (wounds reduced in size by >50% within 4 weeks and predicted to close by 12 weeks).44

The quantitative observations made during the study are also reflected in qualitative clinical observations made during treatment. Positive changes in the wound bed were typically noted 2 to 4 weeks following initiation of OFM treatment, such as the initial resolution of underlying inflammation, development of robust granulation tissue, and the advancement of epithelial tissue leading to closure. These clinical observations underlie the clinical performance of the OFM technology transitioning a wound from the chronic stalled state to the proliferative state.


Although the results of the current case series are promising, the study does have the typical limitations of an uncontrolled case series including the potential for patient selection bias, lack of comorbidities analysis, lack of a control group, and limited sample size. However, findings from this case series do support a larger comparative controlled study or analysis of a large real-world data set to understand the relative efficacy of the OFM across various wound types and its potential impact on the economics of wound healing.


This represents the first Canadian evaluation of the utility of an ovine ECM for the management of chronic wounds. This strategy led to improvements in granulation tissue formation, resulting in the resolution of otherwise stalled chronic wounds. The availability of this advanced technology to Canadian wound specialists provides another tool to manage these complex pathologies. This could be the first step for further Canadian clinical studies and clinical adoption to embed ovine ECM in day-to-day wound management.


1. Frantz C, Stewart KM, Weaver VM. The extracellular matrix at a glance. J Cell Sci 2010;123(Pt 24):4195–200.
2. Schultz GS, Davidson JM, Kirsner RS, Bornstein P, Herman IM. Dynamic reciprocity in the wound microenvironment. Wound Repair Regen 2011;19(2):134–48.
3. Schultz GS, Wysocki A. Interactions between extracellular matrix and growth factors in wound healing. Wound Repair Regen 2009;17(2):153–62.
4. Hynes RO. The extracellular matrix: not just pretty fibrils. Science 2009;326(5957):1216–9.
5. Hynes RO, Naba A. Overview of the matrisome—an inventory of extracellular matrix constituents and functions. Cold Spring Harb Perspect Biol 2012;4(1):a004903.
6. Kaul H, Ventikos Y. Dynamic reciprocity revisited. J Theor Biol 2015;370:205–8.
7. Schultz GS, Ladwig GP, Wysocki A. Extracellular matrix: review of its roles in acute and chronic wounds. World Wide Wounds. August 2005. Last accessed June 10, 2020.
8. Lobmann R, Ambrosch A, Schultz G, Waldmann K, Schiweck S, Lehnert H. Expression of matrix-metalloproteinases and their inhibitors in the wounds of diabetic and non-diabetic patients. Diabetologia 2002;45(7):1011–6.
9. Badylak SF, Freytes DO, Gilbert TW. Extracellular matrix as a biological scaffold material: structure and function. Acta Biomater 2009;5(1):1–13.
10. Badylak SF. Xenogeneic extracellular matrix as a scaffold for tissue reconstruction. Transpl Immunol 2004;12(3-4):367–77.
11. Hodde J. Naturally occurring scaffolds for soft tissue repair and regeneration. Tissue Eng 2002;8(2):295–308.
12. Gilbert TW, Sellaro TL, Badylak SF. Decellularization of tissues and organs. Biomaterials 2006;27(19):3675–83.
13. Hoshiba T, Lu H, Kawazoe N, Chen G. Decellularized matrices for tissue engineering. Expert Opin Biol Ther 2010;10(12):1717–28.
14. Yildirimer L, Thanh NT, Seifalian AM. Skin regeneration scaffolds: a multimodal bottom-up approach. Trends Biotechnol 2012;30(12):638–48.
15. Lu T, Li Y, Chen T. Techniques for fabrication and construction of three-dimensional scaffolds for tissue engineering. Int J Nanomed 2013;8:337–50.
16. Meyer M. Processing of collagen based biomaterials and the resulting materials properties. Biomed Eng Online 2019;18(1):24.
17. Lun S, Irvine SM, Johnson KD, et al. A functional extracellular matrix biomaterial derived from ovine forestomach. Biomaterials 2010;31(16):4517–29.
18. Sizeland KH, Wells HC, Kelly SJR, et al. Collagen fibril response to strain in scaffolds from ovine forestomach for tissue engineering. ACS Biomater Sci Eng 2017;3(10):2550–8.
19. Ricard-Blum S. The collagen family. Cold Spring Harb Perspect Biol 2011;3(1):a004978.
20. Dempsey SG, Miller CH, Hill RC, Hansen KC, May BCH. Functional insights from the proteomic inventory of ovine forestomach matrix. J Proteome Res 2019;18(4):1657–68.
21. Irvine SM, Cayzer J, Todd EM, et al. Quantification of in vitro and in vivo angiogenesis stimulated by ovine forestomach matrix biomaterial. Biomaterials 2011;32(27):6351–61.
22. Negron L, Lun S, May BCH. Ovine forestomach matrix biomaterial is a broad spectrum inhibitor of matrix metalloproteinases and neutrophil elastase. Int Wound J 2014;11(4):392–7.
23. Street M, Thambyah A, Dray M, et al. Augmentation with an ovine forestomach matrix scaffold improves histological outcomes of rotator cuff repair in a rat model. J Orthop Surg Res 2015;10:165.
24. Liden BA, May BC. Clinical outcomes following the use of ovine forestomach matrix (Endoform dermal template) to treat chronic wounds. Adv Skin Wound Care 2013;26(4):164–7.
25. Lullove EJ. Use of ovine-based collagen extracellular matrix and gentian violet/methylene blue antibacterial foam dressings to help improve clinical outcomes in lower extremity wounds: a retrospective cohort study. Wounds 2017;29(4):107–14.
26. Ferreras DT, Craig S, Malcomb R. Use of an ovine collagen dressing with intact extracellular matrix to improve wound closure times and reduce expenditures in a us military veteran hospital outpatient wound center. Surg Technol Int 2017;30:61–9.
27. Simcock J, May BC. Ovine forestomach matrix as a substrate for single-stage split-thickness graft reconstruction. Eplasty 2013;13:e58.
28. Simcock JW, Than M, Ward BR, May BC. Treatment of ulcerated necrobiosis lipoidica with ovine forestomach matrix. J Wound Care 2013;22(7):383–4.
29. Gonzalez A. Use of collagen extracellular matrix dressing for the treatment of a recurrent venous ulcer in a 52-year-old patient. J Wound Ostomy Continence Nurs 2016;43(3):310–2.
30. Ferzoco FJ. Early experience outcome of a reinforced bioscaffold in inguinal hernia repair: a case series. Int J Surg Open 2018;12:9–11.
31. Boyar V. Collagen: providing a key to the wound healing kingdom. Wound Manage Prevention 2019;65(8):12–4.
32. Sen CK, Gordillo GM, Roy S, et al. Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen 2009;17(6):763–71.
33. Rice JB, Desai U, Cummings AK, Birnbaum HG, Skornicki M, Parsons NB. Burden of diabetic foot ulcers for Medicare and private insurers. Diabetes Care 2014;37(3):651–8.
34. Cullen B, Smith R, McCulloch E, Silcock D, Morrison L. Mechanism of action of PROMOGRAN, a protease modulating matrix, for the treatment of diabetic foot ulcers. Wound Repair Regen 2002;10(1):16–25.
35. Shi L, Ramsay S, Ermis R, Carson D. In vitro and in vivo studies on matrix metalloproteinases interacting with small intestine submucosa wound matrix. Int Wound J 2011;9(1):44–53.
36. Champion S, Bohn G. Dressing appearance at change can give insight into dressing effectiveness in the wound. Paper presented at the Clinical Symposium on Advances in Skin & Wound Care; Spring 2015; New Orleans, LA.
37. Bohn GA, Gass K. Leg ulcer treatment outcomes with new ovine collagen extracellular matrix dressing: a retrospective case series. Adv Skin Wound Care 2014;27(10):448–54.
38. Sibbald RG, Ovington LG, Ayello EA, Goodman L, Elliott JA. Wound bed preparation 2014 update: management of critical colonization with a gentian violet and methylene blue absorbent antibacterial dressing and elevated levels of matrix metalloproteases with an ovine collagen extracellular matrix dressing. Adv Skin Wound Care 2014;27(3 Suppl 1):1–6.
39. Bohn GA, Schultz GS, Liden BA, et al. Proactive and early aggressive wound management: a shift in strategy developed by a consensus panel examining the current science, prevention, and management of acute and chronic wounds. Wounds 2017;29(11):S37–S42.
40. Veves A, Sheehan P, Pham HT. A randomized, controlled trial of Promogran (a collagen/oxidized regenerated cellulose dressing) vs standard treatment in the management of diabetic foot ulcers. Arch Surg 2002;137(7):822–7.
41. Vin F, Teot L, Meaume S. The healing properties of Promogran in venous leg ulcers. J Wound Care 2002;11(9):335–41.
42. Schmutz JL, Meaume S, Fays S, et al. Evaluation of the nano-oligosaccharide factor lipido-colloid matrix in the local management of venous leg ulcers: results of a randomised, controlled trial. Int Wound J 2008;5(2):172–82.
43. Gottrup F, Cullen BM, Karlsmark T, Bischoff-Mikkelsen M, Nisbet L, Gibson MC. Randomized controlled trial on collagen/oxidized regenerated cellulose/silver treatment. Wound Repair Regen 2013;21(2):216–25.
44. Margolis DJ, Allen-Taylor L, Hoffstad O, Berlin JA. The accuracy of venous leg ulcer prognostic models in a wound care system. Wound Repair Regen 2004;12(2):163–8.

biomaterial; chronic wounds; cellular and/or tissue-based product; extracellular matrix; ovine forestomach matrix; wound healing; wound management

Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.