Treating Wounds With an Avascular Component With a Dermal Regenerative Template

Introduction. Partially avascular wounds pose a challenge to wound care surgeons. Objective. The authors reviewed the literature and institutional results on the use of a dermal regenerative template (DRT) over partially avascular wounds to quantify the ability of the DRT to vascularize over these wounds.  Materials and Methods. A review of the literature was performed using Ovid MEDLINE, Google Scholar, and Cochrane Library. Patient demographics, comorbidities, wound types, surface area of avascular tissues, and skin graft take were analyzed. A retrospective review of institutional cases was conducted. Results. A total of 32 articles met inclusion criteria. The retrospective review included 26 patients with partially avascular wounds reconstructed with the DRT. Seventeen patients experienced 100% graft take, 6 experienced partial take, and 3 suffered complete loss. The percent and absolute size of avascular surface area in the wound was significantly lower in cases of complete graft take compared with partial take and complete loss (1.9% and 2.7 cm²; 9.3% and 10.0 cm²; 18.0% and 9.3 cm², respectively, P < .001). Chronic wound status (P < .001) was significantly associated with less graft take. Conclusions. This literature review and retrospective study confirm the DRT is a viable option to provide vascularized coverage over wounds with avascular components. This study suggests the DRT is more reliable in wounds with less than 1.9% avascular tissues and less successful in chronic wounds.

Wounds with avascular components are a common challenge for the wound care practitioner. Avascular components lack blood flow and the potential to heal without intervention. These are vital structures, such as tendon devoid of paratenon, bone devoid of periosteum, or joint surface. Vascular tissues are perfused structures, such as muscle, subcutaneous tissue, or tendon or bone covered by paratenon or periosteum, respectively. Partially avascular wounds are challening due to the multitude of options for closure, including prolonged wound care, flaps, and dermal regenerative templates (DRTs).

The benefits of DRT are generally accepted, including predictable success and minimal donor site morbidity, to outweigh the limitations of high-cost and multiple surgical procedures.^1-7 At the authors’ institution (Rutgers New Jersey Medical School, Newark, NJ), Integra Dermal Regenerative Template (Integra LifeSciences Corporation, Plainsboro, NJ) is used to augment reconstruction to enhance durability of skin grafts and preserve function of the underlying structures. A robust skin graft augmented by the DRT ensures better excursion of muscles and tendons and prevention of pain associated with skin grafting directly over nerves.

Numerous patients with partially avascular wounds are unable to tolerate, or they refuse, more complex reconstructive options. In patients who will undergo skin grafting, the authors’ standard protocol is to obtain a fully vascularized wound bed, consisting of healthy, red granulation tissue, through debridement, negative pressure wound therapy (NPWT), or other dressings prior to application of the skin graft. This technique is well described in the literature^5,8-32 and proved successful in the authors’ patient population. However, the authors recognize there is a large population of patients in whom strict adherence to this protocol is not ideal and may not be necessary.^{1,19,21,33-36} The literature suggests DRTs are a viable option for a large, albeit undefined, segment of these patients. 

Despite the large body of literature demonstrating the success of DRT, no single study has attempted to quantify the ability of DRT to cover partially avascular wounds. The lack of quantified knowledge regarding the ability of DRT to successfully cover wounds with avascular elements is a barrier to its proper and efficient use in the aforementioned patient population.^1,3

The primary objective of this study was to review the literature on the use of DRT in wounds with avascular components to determine if DRT is a viable option for the coverage of partially avascular wounds. The secondary purpose was to evaluate the use of DRT in partially avascular wounds at the authors’ institution and quantify its ability to survive over these wounds. 

Literature review

A systematic review of the literature was performed in Ovid MEDLINE, Google Scholar, and Cochrane Library for the use of DRT on wounds with avascular components. Search queries included “dermal regenerative template” OR “dermal scaffold” OR “Integra” AND “Wounds” OR “bone” OR “tendon” OR “joint” in Ovid MEDLINE. The Google Scholar and Cochrane Library search queries included “dermal templates in avascular wounds”, “dermal scaffolds in avascular wounds”, and “Integra in avascular wounds”. Additional articles were extracted from bibliographies. Searches were limited to studies on humans and published in the English language.

Inclusion criteria allowed for studies analyzing the use of DRT to reconstruct partially avascular wounds in humans. Exclusion criteria disqualified studies evaluating the use of DRT on wounds without avascular components, animal studies, and the use of other extracellular matrix technologies, such as those using fetal bovine collagen, porcine intestinal submucosa, acellular dermal matrix, or amniotic tissues.

Two researchers (R.N.B. and M.A.A.) used identical search protocols to identify articles independently. Initial screening included review of titles and abstracts. The second stage included full text review by the aforementioned researchers. A third and final stage was instituted when an article was chosen by a single reviewer (R.O.D.). In this stage, a third independent researcher made the final decision to include or exclude these articles. 

Retrospective chart review

A retrospective chart review of a single plastic surgeon’s (R.O.D.) cases at Rutgers New Jersey Medical School Division of Plastic Surgery was performed between 2005 and 2017. Patients with wounds with avascular components who underwent reconstruction with the DRT were included. Patients with fully vascularized wounds or wounds reconstructed without the DRT were excluded. The previously mentioned commercial DRT is the only DRT used by this author (R.O.D.).

Surgical techniques generally followed the same pattern, with slight variations depending on infectious or necrotic burden. Serial wound debridement was performed until all wounds were devoid of nonviable debris and intraoperative culture swabs were negative. A culture report of “no growth” after 5 days was considered negative. Total wound size was measured intraoperatively with rulers. The amount of avascularized tissues was recorded inconsistently using similar measurements.

Once a healthy wound bed with minimal avascular tissue was attained, the DRT was applied over the entire wound bed and secured with nonabsorbable monofilament running suture. For inpatients, negative pressure wound therapy, (NPWT; V.A.C. Therapy, KCI, an Acelity Company, San Antonio, TX) was applied at continuous subatmospheric pressure (-100 mm Hg to -125 mm Hg) for 5 to 7 days. Dressing changes occurred every 5 to 7 days in the operating room or at the bedside. For outpatients, petroleum-impregnated, nonadherent gauze-based bolster dressings were secured around the wound beds for 5 to 14 days. The silicone layer was removed once the DRT had incorporated without evidence of infection. Incorporation was demonstrated by salmon coloration of the DRT with adherence to surrounding tissues.

A meshed split-thickness skin graft (STSG) then was applied over the incorporated DRT, usually after 2 to 4 weeks. The STSGs were harvested from the upper thigh and ranged in thickness from 0.008 in to 0.012 in. Patients who were deemed healthy enough for discharge and capable of caring for their own wounds usually were treated in the outpatient setting. Patients who did not meet this criterion or had other medical or social reasons for hospitalization were treated in the inpatient setting. 

Patient demographics, comorbidities, recipient site wound characteristics, chemotherapy or radiotherapy treatment, use of NPWT, type and surface of exposed tissues, and success of subsequent STSG take were compiled and analyzed.

The percentage of skin graft survival (or take) was used as a surrogate for the success of the DRT as the dependent variable in this retrospective review for 3 reasons. First, skin graft take was consistently recorded in the charts, while take of the DRT was not. Second, take of the skin graft is directly dependent upon, and reliably predicts, the prior take of the DRT. Third, while success of the DRT is an intermediary measure, skin graft take is the end goal and demonstrates the overall success of reconstruction for the patient. Thus, throughout this study, skin graft take is used as a substitute for success of the DRT.

The percent and absolute surface area of avascular tissues within a wound were not always reported explicitly in the patient records. Two authors (R.N.B. and M.A.A.) reviewed patient physical examinations and operative reports and independently estimated these values from the available wound descriptions. These estimates then were averaged for the final values included in the study. Complete skin graft take was defined as 100% take, partial take was defined as less than 100% but greater than 0% take, and complete loss was defined as 0% take.

IBM SPSS Version 25 (IBM, Armonk, NY) was used to calculate Fisher’s exact test, one-way analysis of variance, and Tukey post-hoc tests. These were used to analyze nominal and quantitative variables, respectively. Statistical significance was set at P < .05. The data were not reviewed or influenced by an outside party at any point during this study.

Literature review

The literature review produced 32 articles meeting the inclusion criteria. The Ovid MEDLINE search returned 32 PubMed-indexed articles (Table 1, Table 1 cont.^{1,2,4,6-8,18,19,22,29,32-35,37-54}). The Cochrane Library search returned no Cochrane Reviews on the use of DRT in partially avascular wounds. The Google Scholar search returned 3 international articles not indexed in Ovid MEDLINE. Articles in that review included 1 prospective clinical trial, 1 prospective case-control study, 5 prospective observational studies, 2 comprehensive literature reviews, 13 retrospective reviews, 3 case series, and 7 case reports.

The literature demonstrated positive outcomes for the use of DRT in partially avascular wounds in several anatomic locations and wounds of diverse etiology. Wound locations over the entire body were treated, including the scalp, trunk, and extremities. Exposed avascular structures included bone, tendon, and joint. Several techniques for wound preparation, DRT application, dressings, and time to skin graft were described, all with good results (71%–100% STSG take; mean, 90%).

Techniques were evaluated (Table 2). Debridement techniques varied depending on wound condition, necrosis, and infectious burden. In all cases of exposed calvarium, the outer table was burred down to bleeding diploic bone.^{1,6,18,34,37-39} Similar strategies were used elsewhere on exposed bone, such as drill holes in exposed tibia by Yeong et al³⁹ and Verbelen et al⁴⁰ and abrasion by Smock et al³⁵ and Chen et al.⁴¹

All authors placed DRT directly over tendon and joint with superb results.^{4,7,15,19,32,38,43-49} Tendon excursions or adhesions were not explicitly described as outcomes in most cases.  

The commercial DRT studied herein was the DRT applied in all but 2 studies in the literature. Verbelen et al⁴⁰ and Pirayesh et al⁵⁵ applied Glyaderm (Amsterdam Plastic Surgery, Amsterdam, Netherlands) after the study DRT failed, and Alet et al⁴ applied Perouse Plastie (Perouse Plastie SAS, Bornel, France) primarily. These 2 groups experienced nearly complete take of STSGs applied over their alternative DRTs. 

The literature demonstrated alternatives to the standard 2-staged approach of DRT application followed by STSG at 2 to 4 weeks. Ghazi and Williams¹⁸ and Alagaratnam et al⁴² did not apply STSGs to the DRT. Rather, they allowed the DRT to epithelialize over pediatric and diabetic wounds, respectively, resulting in complete wound healing. Koenen et al³⁴ applied the DRT and a STSG in a single stage under a bolster to facial wounds, which also resulted in complete graft take.

Several bolstering and dressing change techniques were described in the literature. Negative pressure wound therapy was used in about 16% of all cases with no influence on DRT or STSG take (STSG take range, 92%–100%).^{8,19,40,42,44,46,47,49-52} Antibiotic and silver-impregnated bolster dressings frequently were utilized as methods to secure the DRT, and all showed good to excellent results (STSG take range, 87%–100%).^{7,19,22,32,34,41,53} González et al,⁵¹ Koenen et al,⁵² and Konofaos et al⁵⁴ combined silver-impregnated dressings with NPWT, also showing good results. The use of NPWT versus other bolster and dressing methods seemed to depend on institutional and surgeon preference rather than wound characteristics.

The literature demonstrated a broad range of time intervals from DRT placement to application of STSG. The time interval ranged from 11 to 35 days (mean, 20.1 days). The most common complication encountered was infection, which commonly was treated with the removal of a silicone layer, debridement of infected segments, and NPWT with good success. On several occasions, infection resulted in DRT or STSG failure, requiring a more complex reconstruction. Other complications included late STSG wounds, joint contraction, or subtotal STSG take. Frequently, repeated attempts of DRT application were successful.

Retrospective chart review

Twenty-six patients met inclusion criteria. The average patient age was 43 years, with a body mass index of 28.9 kg/m². Of the 26 patients, 14 (53.8%) were male and 18 (69.2%) smoked. The total wound size was 153 cm², and avascular structure size was 5.5 cm² (Table 3). Twenty-one patients (80.8%) had a history of NPWT use prior to reconstruction with DRT. Negative pressure wound therapy was stopped as a primary mode of wound care in these patients when they reached a plateau of granulation formation. The use of NPWT was not significantly related to the success of the DRT. There were no statistically significant demographic differences identified between the complete, partial, and no take groups. 

There was complete skin graft take in 17 patients, partial graft take in 6, and no graft take in 3. The percent of the wound that was avascular and the absolute avascular area were significantly different between the 3 groups of graft take (Figure 1). The percentage of avascular surface area of wounds was statistically significantly lower in the complete graft take group (1.9%) compared with the partial graft take group (9.3%, P = .001) and the no graft take group (18.0%, P < .001). The difference between partial and no graft take also was statistically significant (9.3% vs. 18.0%, P = .006).

Absolute avascular area of wounds was statistically significantly lower in the complete graft take group (5.1 cm² ± 4.7 cm²) compared with the partial graft take group (10.0 cm² ± 5.7 cm², P < .001) and the no graft take group (9.3 cm² ± 5.1 cm², P = .012). There was no statistically significant difference between the partial and no graft take groups (P = .958). 

Exposed avascular structures included bone and tendon with 12 and 14 patients in each group, respectively. In the exposed bone group, there were 7 complete graft takes, 4 partial graft takes, and 1 no graft take. In the exposed tendon group, there were 10 complete graft takes, 2 partial graft takes, and 2 no graft takes (Figure 2). There was no difference in exposed structure size (P = .135) or avascular area (P = .107) when comparing bone and tendon groups. 

Wound etiologies included trauma (12), oncology or benign mass (5), chronic venous insufficiency (4), diabetes mellitus (3), peripheral vascular disease (1), and infection (1) (Figure 3). These were further delineated as acute (< 6 months’ duration [16]) and chronic (> 6 months’ duration [10]). Chronic wound status (P < .001) was significantly associated with poor graft take.

Case example

Figure 4 demonstrates the case of a 27-year-old male who was a right-hand dominant smoker, otherwise healthy, and presented after a traumatic circumferential degloving injury to the right arm. He was brought to the operating room for serial debridements as his soft tissues demarcated. The DRT was applied to cover 6 cm² of exposed extensor tendons, exposed radial artery, and sensory nerves. The case photos demonstrate superb wound healing and range of motion. There was no evidence of hypersensitivity or neuroma formation. 

Wounds with avascular components pose significant challenges to the wound care clinician due to the necessity of intervention to obtain wound closure. Treatment options include flaps, long-term dressing changes until the wound bed is covered by granulation tissue prior to skin grafting, or DRT. The literature has demonstrated DRT as a powerful reconstructive tool.¹

The authors’ standard protocol is to apply DRT over fully vascularized wound beds achieved by local wound care. In this scenario, DRT augments the reconstruction, resulting in a STSG that enhances the function of the underlying structures and reduces pain. Less defined, however, is the ability of DRT to succeed in patients with partially avascular wounds, who are not candidates for, or refuse the traditional reconstructive options. The present study attempted to determine the viability of DRT in wounds with avascular components. This knowledge may lead to a more standardized approach for the use of DRT in this patient population. To date, the literature has not produced specific, quantitative recommendations for the use of DRT in these types of wounds.

The systematic literature review demonstrated excellent STSG take (87%–100%) in partially avascular wounds of diverse etiology and location.^{1,2,4,7,8,18,19,22,29,32-35,37,38,40,41,43,44,46-48} These data show a fully vascularized wound bed is not an absolute requirement for the success of DRT and subsequent STSG take. Overall, a strict adherence to aggressive wound debridement was documented in all 32 articles that met inclusion criteria. Most authors debrided or fenestrated bone to attain a bleeding surface. While the exact surface area of non-bleeding, exposed bone was not disclosed, this demonstrates the ability of DRT to vascularize through ingrowth from surrounding vascular tissues. Similarly, all groups with DRT placed directly over exposed tendon devoid of paratenon experienced good results, presumably from vascular ingrowth from adjacent vascularized parts. 

The techniques to bolster DRT in the literature differed in several ways. The most common methods included NPWT (16% overall)^{8,19,40,42,44,46,47,50,51,54} and antibiotic or silver-based dressings.^{1,2,7,18,22,32,37,39,43,45,52,53} The frequency of dressing changes varied significantly. None of these techniques influenced STSG take and seemed to be based on institutional and surgeon preference rather than wound characteristics. The STSGs were applied at variable times, but always when the DRT was noted to be well vascularized. The STSG application ranged from 11 days to 35 days, with a mean of 20.1 days. Time of STSG application did not affect STSG take.

There were several notable deviations from the standard 2-stage application of the DRT described in the literature. These included the epithelialization by secondary intention of the studied DRT without STSG,^18,42 the use of DRT other than the studied DRT herein,^4,40 and the application of the studied DRT and a STSG in a single stage.³⁴ Each of these strategies resulted in excellent outcomes, which the authors define as greater than 90% STSG take in any time period. 

Strengths of this systematic literature review included its demonstration of variable techniques, and its provision of a large body of 428 cases. The literature established the use of DRT in partially avascular wounds as a viable reconstructive option. The literature confirmed the fenestration of bone as a viable technique to produce a wound bed amenable to DRT survival. Weaknesses include significant heterogeneity of the literature stemming from the novelty of DRT; lack of double-blinded, randomized clinical trials and meta-analyses; and wound, patient, surgeon, and institutional variability. There is a high likelihood of positive-result publication bias. The literature also failed to provide specific guidelines for the use of DRT in partially avascular wounds based on any metric, such as percent of the wound that is avascular, wound etiology, location, or type of exposed structure (except for bone). 

The retrospective chart review similarly confirms the ability of the studied DRT to provide vascularized coverage over wounds with avascular elements. This is the first study attempting to describe, based on specific qualitative metrics, the ability of the studied DRT to survive over partially avascular wounds. The data suggest this DRT is more successful in wounds with less than 1.9% to 9.3% avascular tissues (P ≤ .001). Chronic wounds (> 6 months’ duration) were associated with poorer graft take (P ≤ .001). Notably, the data indicate the success of this DRT may depend more on percent of avascular tissue exposed rather than absolute surface area of avascular tissues. A statistically significant difference between percent avascular surface area for partial graft take (9.3%) and complete graft loss (18%) was demonstrated. However, these same groups had equal absolute surface areas of avascular tissues (10.0 cm² ± 5.7 cm² and 9.3 cm² ± 5.1 cm²). This indicates the ratio of the avascular component to the total wound area may be more important than absolute surface area when assessing the healing potential of chronic wounds with the use of DRT.

Weaknesses of this study stem from its retrospective design. While the total wound dimensions were accurate for all patients, the greatest limitation of the study was the lack of exact wound dimensions of the avascular components. Two researchers (R.N.B. and M.A.A.) independently reviewed charts, physical exams, and operative reports to estimate the total surface area of avascular versus vascular structures in wounds. These two estimates were averaged for the final data. This was an attempt to reduce the human error that is inherent in this type of retrospective review. 

The percent of the studied DRT survival was not well described in the records. Thus, STSG take served as a surrogate for DRT success, which was similar to results in the literature.

The STSG partial take was defined as less than 100% but greater than 0% take. Due to a lack of power, the STSG partial take category was not further quantified to subcategorized beyond this range. This introduces a level of obscurity regarding the ultimate endpoint of successful wound healing.

There is an additional selection bias in the present study, as patient selection was nonrandom. The senior author (R.O.D.) selected patients for the application of the studied DRT only after achieving a healthy wound bed with minimal avascular elements relative to the vascularized components. This strategy purposely lead to significant neovascularization from the vascularized wound components with relatively small contributions from the periphery. The data indicate the use of DRT in wounds with avascular components of more than 18% is not successful. However, the senior author purposefully choose alternative reconstructive options in patients with greater proportions of avascular tissues, which may invite a level of selection bias. Wounds with larger proportions of avascular tissues typically go on to receive more complex reconstructive efforts at the authors’ institution. Thus, the authors cannot firmly state a specific threshold percentage of avascular tissues that DRT cannot successfully cover.  

Negative pressure wound therapy has been demonstrated to enhance the success of DRT.³ In this patient population, NPWT was nonrandomly assigned. Smaller wounds in healthier patients were more likely to be treated with bolsters on an outpatient basis. Larger wounds in patients who required hospital admission were more likely to receive NPWT. This nonrandom selection skews the data to obscure the potentially beneficial effects of NPWT. Thus, the authors are unable to make conclusions on the use of NPWT.

Furthermore, the study is limited to the use of the studied DRT only — the authors recognize that other templates have been used for similar purposes. The studied DRT was the only DRT available at the authors’ institution at the time of patient care.  

This systematic literature review and retrospective chart review demonstrate DRT is a viable option for reconstruction of partially avascular wounds. Clinical judgment and experience, coupled with an individualized approach, should guide the use of this DRT. The literature demonstrates that aggressive debridement and eradication of infection are essential, but the use of NPWT, bolster technique, frequency of dressing changes, and time to STSG are not clearly associated with the success of the studied DRT over partially avascular wounds. The literature review failed to provide any specific guidelines for the application of DRT to partially avascular wounds regarding wound size, percentage or type of avascular components, wound etiology or location, or patient comorbidities except that the fenestration of bone is a viable technique for DRT success.

This is the first study attempting to describe, quantitatively, the ability of the studied DRT to successfully reconstruct partially avascular wounds. While limited by its retrospective design, this study suggests this DRT is more successful in wounds with less than 1.9% to 9.3% avascular tissues and less successful in chronic wounds. The results support the feasibility and safety of a future prospective study to quantify the ability of this DRT to survive over avascular tissues. Such a study may generate specific, standardized guidelines. 

Authors: Ronald N. Bogdasarian, MD; Erica Y. Xue, MD; Marvin Argüello-Angarita, MD, MPH; and Ramazi O. Datiashvili, MD, PhD

Affiliation: Rutgers University New Jersey Medical School, Newark, NJ

Correspondence: Ronald N. Bogdasarian, MD, PhD, Rutgers University New Jersey Medical School, Division of Plastic Surgery, 130 Bergen Street, ACC Building E-Level, Newark, NJ 07102; rb909@njms.rutgers.edu

Disclosure: The authors disclose no financial or other conflicts of interest.