Use of Collagen Powder in Secondary Intention Healing After Mohs Surgery or Excisional Surgery: A Retrospective Study

Interest is growing in secondary intention healing after Mohs surgery and excisional surgery. Benefits include fewer restrictions on patients’ postoperative activity, fewer concerns about dehiscence, and better control over bleeding, using pressure or light cautery. Surveillance is easier, hematoma formation is unlikely, and cost savings are substantial.¹ As Mohs surgeons gain experience, they allow more wounds to heal by secondary intention.²

Surgeons may select secondary intention healing for patients who have had a wound dehiscence, flap necrosis, or infection; those who have undergone skin cancer excisions; older patients; and patients with large, recurrent, aggressive, or high-risk tumors.¹ Secondary intention healing poses challenges: possible pain, desiccation, infection, as well as risks of trauma associated with exposed underlying tissue.

To be considered biologically ideal, wound dressings—including commercial biologic dressings composed of human, nonhuman (xenograft),^3,4 or partially synthetic tissue⁵—would be safe for patients, clinically effective, convenient to handle and apply, low cost, and widely available, with a long shelf life. They would be biodegradable, yet stable enough to support normal tissue reconstruction, including reepithelialization, and would not trigger an immunogenic response, transmit disease, be cytotoxic, or cause excessive inflammation. Collagen powder has received FDA and CMS clearance for the management of full-thickness surgical wounds with light exudate.⁶ Several manufacturers produce collagen powder for the dermatology market, but to the knowledge of the authors of the current study, this study is the first to describe the clinical utility of collagen powder. This study was undertaken to test whether collagen-assisted granulation may decrease healing time, improve cosmetic outcomes relative to granulation with petroleum jelly, and be more cost effective than xenograft, surgical closure, or skin grafts. Participants who chose powdered collagen for wound closure instead of xenograft or other forms of closure were enrolled in the study.

After receiving institutional review board approval (Sterling IRB number 8611), a retrospective cohort review was done of all applications of collagen powder to augment secondary intention wound healing at the Georgia Skin and Cancer Clinic in Savannah, Georgia, between January 2020 and January 2022. The collagen, which was supplied by MPM Medical, is cleared by the FDA for use in partial- and full-thickness wounds, including surgical wounds (FDA 510k Approved MPM Medical, 1801 Big Town Blvd, Suite 800, Mesquite, TX 75149). The collagen is processed from sources free of bovine spongiform encephalopathy, and it is a nonhydrogenated bovine type I collagen that is prepared by a chemical-free process and depyrogenated to remove any endotoxins.

Complete.MD DME, LLC markets the collagen powder as Complete.MD Triple Helix Collagen (hereafter “CMD nonhydrogenated bovine type I collagen”) for dermatologic surgeons to aid healing of Mohs and excisional surgical wounds. The senior author (S.P.S.) has no financial interest in the collagen manufacturer (MPM Medical), but distributes the nonhydrogenated bovine type I collagen to patients in compliance with CMS DMEPOS guidance. Providers order and provide supplies such as CMD collagen within their normal scope of services. 

Before surgery, closure options and the risks and benefits of each option were discussed with the patients. As clinically appropriate, the options included primary closure, flaps, full-thickness skin graft, partial-thickness skin graft, granulation with petroleum jelly, and collagen-assisted granulation. Patients who chose collagen-assisted granulation as their preferred closure option were included in the study.

Patients who underwent Mohs surgery or excisional surgery and who chose collagen-assisted granulation for secondary intention healing received a so-called day of surgery kit containing CMD nonhydrogenated bovine type I collagen (1-g package), normal saline (8 oz), a nonadherent pad, Hypafix tape (BSN Medical), collagen wound care instructions, a patient agreement covering collagen wound care, an informed consent document, a surgical note covering collagen powder, as well as the following CMS DME–compliant materials: office note, collagen prescription, and DME supplier standards and patient rights and responsibilities.

Patients were instructed in how to mix the CMD nonhydrogenated bovine type I collagen with normal saline to the consistency of petroleum jelly and were instructed to apply the collagen jelly to the wound twice daily, showering or bathing as usual. The need to keep the wounds moist, never allowing them to dry out, was emphasized.

A separate kit was shipped the day after surgery which included 15 CMD nonhydrogenated bovine type I collagen powder bags (1 g each), 15 sterile bordered gauze pads (4 in × 3 in), and a patient DME questionnaire (a CMS requirement).

Patients were seen in the clinic, initially weekly, then every 2 to 3 months, depending on the extent of wound healing. Medical records were reviewed, noting any immunosuppressant medications, the type of surgery (Mohs or excision), tumor type, tumor location, area of surgical defect, and patient age, self-reported race, anticoagulant use, and smoking history.

To complete the DME questionnaire, all patients were contacted by telephone, and 62 of these patients were reached in person for wound assessment using the VSS and the POSAS. These tools are validated and accepted for assessing burn and postoperative scars.

The VSS has 4 variables: vascularity, thickness, pliability, and pigmentation, each with 4 to 6 possible values. A total score ranges from 0 to 14, with 0 indicating normal skin.⁷

The POSAS consists of 2 scales. In the patient scale, the patient scores 6 items: scar color, pliability, thickness, relief, itching, and pain. For the observer scale, the observer scores 5 items: scar vascularization, pigmentation, pliability, thickness, and relief.⁸ Each item is scored from 1 to 10, with 10 indicating the worst imaginable scar or sensation. The total score of the patient scale is calculated by adding the scores of each of the 6 items (range, 6–60), and the total score of the observer scale is calculated by adding the scores of each of the 5 items (range, 5–50). The lowest scores, 6 and 5, respectively, indicate normal skin.⁹ 

In the current study, duration of healing was assessed based on patient recollection, because some patients lived far from the clinic and were seen on follow-up only if their wounds were not progressing to complete granulation.

Multivariate statistical analyses were performed using the t test, Pearson chi-square test, and linear regression.

Data in Table 1 characterize the 266 patients who used CMD collagen to augment secondary intention wound healing, and Table 2 shows the characteristics of the 266 lesions treated with CMD collagen.

Mohs surgery was performed on 123 patients in this group (46.2%), and excisional surgery was performed on 143 patients (53.8%). The mean area of surgical defect was 6.0 cm² (range, 0.40 cm²–56.12 cm²). All wounds were allowed to granulate with only collagen application. Patient case examples are seen in Figures 1–4. Ten patients (3.8%) needed antibiotics for infection, and 16 (6.0%) had prescriptions for narcotics for pain. Four patients (1.5%) had postoperative bleeding requiring an office visit.

Investigators tried to follow each patient until complete healing could be documented, but typical distances made this nearly impossible. Instead, patients assessed their complete healing time. Their estimates averaged 6.3 weeks for complete healing (range, 1–32 weeks; 50th percentile, 5 weeks). No correlation existed between length of time for healing and any of the following: anticoagulant use, immunosuppression, smoking, type of surgery, sex of patient, use of narcotics or antibiotics, and postoperative bleeding.

All wounds healed without additional intervention. One-way analysis of variance identified a statistically significant difference between defect location and time needed for healing of the lower extremity and foot relative to other areas (Table 3; Figure 1). Regression analysis showed a linear relationship between the area of defect and the number of weeks required for healing, with each 1.0 cm² increase in defect area adding another 1.4 days (0.2 weeks) to the time needed for healing.

Of the 266 patients in the study group, 216 (81.2%) had previously had a skin cancer removed. In 90 patients (33.8%), removal occurred on the hand or on the leg, below the knee (Figure 1, Figure 4). When asked about their preference in wound care, 200 patients (75.2%) chose application of powdered collagen, 33 (12.4%) chose flap coverage, 32 (12%) chose graft coverage, and 1 (0.4%) chose granulation healing. The mean patient score for ease of use and overall impression of collagen application was 8.07 (Table 4).

During later in-person visits, 63 patients (24.0%) assessed their post-granulation scar. Table 5 shows the results of the POSAS and the VSS.

Application of collagen for granulation assistance is the most economical closure option. With no return visit at 1 week for suture removal, a cost to the average caretaker of $313.50 (Table S2), and no need to purchase additional supplies from the pharmacy, the cost savings to the patient and family are significant. Collagen for granulation supplied by the physician ($128.07) is 41% less expensive than the patient’s cost of purchasing supplies ($63) with the help of a caretaker (3 hours plus mileage $180.56) (Table S1, Table S2). Also, the cost of collagen-assisted granulation is 356% less expensive than a full-thickness skin graft ($455.80) and 305% less expensive than a complex repair ($391.10) (see Supplementary Tables for the detailed analysis).

In appropriate clinical settings, most experienced surgeons prefer secondary intention over primary surgical repair. Secondary intention carries fewer postoperative restrictions, with less concern about dehiscence. Bleeding is unlikely, surveillance is easier, and cost savings are substantial.^1-3 Several retrospective studies describe the usefulness of secondary intention after Mohs surgery and excisional surgery, as well as the benefits of using collagen or other biologic dressings to cover and protect postoperative secondary intention wounds.^1-5,10 

A study of 200 patients treated at Mayo Clinic³ and a study of 128 patients treated at UT Southwestern Medical Center⁴ demonstrated the suitability of porcine xenografts with collagen substrate for augmenting secondary intention wound healing. By mimicking native skin, the xenografts reduced pain, limited desiccation, and simplified wound care. Other durable skin substitutes under development include allografts, cultured skin grafts, dermal substitutes, and biosynthetic dressings.^11-13 

Collagen-based wound dressings have long been used to cover burns and treat skin ulcers.^14-16 These dressings have a distinctive practical and economic advantage over growth factor and cell-based treatment of full-thickness wounds and have been used as artificial dermis in reconstruction after cutaneous surgery in elderly patients.¹⁷ These dressings have been formulated in a number of ways.¹³ Powdered collagen expedites chronic wound healing and promotes cellular recruitment and activation of the inflammation phase of wound healing.¹⁸ It also supports new tissue growth.¹³ Because of its mechanical strength and biocompatibility, type I collagen can be placed directly on damaged skin.¹⁹ Processed to minimize cross-linking, this collagen can exert its biologic activity immediately upon application.²⁰ 

The method of collagen preparation has a critical effect on how the collagen will perform in treating healing wounds. Options include physical manipulation (snap freezing or high pressure), chemical application (acid or alkali treatment, chelation with EDTA, or treatment with detergents or solutions of high osmolarity), and enzymatic preparation (digestion with trypsin).¹³ The current study used a nonhydrogenated bovine type I collagen, prepared by a chemical-free process and depyrogenated to remove any endotoxins.

Most patients had undergone skin cancer removal before the current procedure, with a variety of types of closure used. This gave the patients a basis for judging the desirability of using powdered collagen. Most patients preferred collagen over a skin graft and would recommend collagen to a friend. Most patients had no pain associated with collagen application.

The average defect size in the cohort in the current study, 6.0 cm² (range, 0.40 cm²–56.12 cm²), was similar to the average in the Mayo cohort, 5.7 cm² (range, 0.42 cm²–84 cm²),³ and smaller than the average in the UT Southwestern Medical Center cohort, 7.4 cm² (range, 0.13 cm²–64 cm²).⁴

The size of the defect correlated with the length of time to complete healing. The mean healing time by patient estimate was 6.3 weeks (range, 1–32 weeks). No effect on healing time was found with smoking; patient sex; use of anticoagulants, antibiotics, or pain medications; immunosuppression; postoperative bleeding; or surgery type.

Postoperative infections and bleeding were minimal, with a rate similar to that reported for sutured and secondary intention wounds (3.9%) but lower than the infection rate reported in other studies (6.8% for secondary intention wounds).²⁰ Other reports cite a rate of infection complication for full-thickness skin grafts of lower leg defects after excisional surgery between 6.7% and 18%.^21,22 An infection rate of 6.2% was found in the xenograft study at Mayo Clinic,³ with a rate of 3.1% in the series at UT Southwestern Medical Center⁴ and a rate of 4.08% reported in a meta-analysis of 18 studies with 33 086 patients.²³ 

The current study found no statistical difference in location of defect and need for antibiotics. Postoperative bleeding requiring a visit occurred in 1.5% of cases. The Mayo Clinic xenograft cohort had an incidence of bleeding of 6.2%,³ but the UT Southwestern Medical Center cohort reported no bleeding incidents.⁴ In the cohort in the current study there was no statistical association between bleeding and defect location.

Most of the patients in the current study had no pain, but 6.0% required narcotic pain medications. The reported incidence of pain was similar to that in the Mayo Clinic patients treated with xenograft (3.1%)³ and the UT Southwestern Medical Center cohort (8.6%).⁴

The POSAS and the VSS were used as the scar assessment tools for 63 patients in the current study cohort. Based on their experience with skin grafting, 75.2% of patients preferred the use of collagen.

The VSS and the POSAS scoring systems were reported in a case series assessing facial skin graft scars in 23 patients who underwent Mohs surgery.²⁴ In that case series, the mean total VSS score for facial skin graft scarring was 3.4 ± 1.822—slightly better than the mean VSS score of 4.3 in the current study, for all anatomic areas. In Chae et al,²⁴ the provider score for the nasal graft scar component of the POSAS was 15.5 ± 7.5, and the patient POSAS score was 17.4 ± 9.6. In the 5 nasal cases in the current study, the average VSS score was 2.8 ± 1.1, the patient POSAS score was 14.0, and the observer POSAS score was 12.8, which was better than the POSAS and VSS nasal skin graft averages. Although it is hard to compare POSAS and VSS scores between studies, these findings in the current study suggest that collagen-assisted secondary intention healing may be comparable, if not superior, to nasal skin grafting. 

The use of collagen powder to enhance wound closure and final cosmetic appearance was investigated in a study of 111 granulating wounds in patients who underwent Mohs surgery.²⁵ The authors of that study reported no difference in the rate of wound epithelialization or final cosmetic appearance in patients who had received collagen. The authors of a rat model found that topical application of type I collagen did not facilitate wound healing.²⁶ In a study in which 4-mm punch biopsies were treated daily with collagen powder and left to heal by secondary intention, it was found that collagen powder offered superior cosmetic outcomes compared with primary closure with suture, and, based on histopathology results, may improve strength and maturity of the healing wound.²⁷

Researchers and surgeons assume that all collagen powders provide the same treatment. However, because many different processes are used to create the biomaterial, collagen products may elicit quite different clinical responses. Processing with no added chemicals may provide an advantage to the CMD collagen. How collagen is processed and what methods are used to manipulate the tertiary structure and attachments may have a clinical effect.

The current study demonstrates the value of powdered collagen as a secondary intention healing aid for Mohs and surgical wounds. The results are quite similar to those with the use of porcine xenografts.³ Collagen powder can be safe and well tolerated, and it can be broadly used in many areas of the body. In the practice of the authors of the current manuscript, collagen powder is used as a substitute for split- and full-thickness skin grafts in most anatomic areas.

This study has limitations. The sole purpose of this study was to investigate the utility of a single proprietary collagen for the patient and practitioner, not to compare various collagen agents or granulation assistant substances such as porcine skin grafts, tissue-engineered skin substitutes, or routine local wound care with petroleum jelly. To limit reviewer bias, team members other than the lead author performed the prospective assessments of scar outcomes and patient questionnaires. Although evaluating healing dates with weekly visits would have been preferable, due to the distance traveled by patients it was necessary to rely on patient recall of healing reflected by last use of collagen. Although patient recall bias is possible, there was consistency between patients in the time to healing. 

A prospective study is warranted to clarify whether collagen powder, xenografts, or secondary intention improve healing time, cosmetic results, and postoperative pain. A way to compare secondary intention–assisted wound healing with wound healing by use of the many biologic skin substitutes on the market is needed. Use of the VSS and the POSAS may help in comparing studies. The results of the current study indicate that when clinically appropriate, granulation assisted by collagen powder should be considered for augmenting secondary intention healing. 

Authors: Lauren Kendall, BS; Demetrius Hurst, BS, MS; John Monahan, BS; and Sidney P. Smith III, MD

Affiliation: Georgia Skin and Cancer Clinic, Savannah, GA

Disclosure: The statistical analysis was funded by Mercer University School of Medicine, Savannah, Georgia. The research was funded by Sidney P. Smith III, MD, founder and CEO of Complete.MD DME, LLC, which assists with practice CMS/Medicare DME compliance and markets CMS/FDA approved collagen powder. Final editing of this manuscript was provided by Clyde R. Goodheart, MD, MBA, MS. All other authors disclose no financial or other interest in Complete.MD DME, LLC. 

Correspondence: Sidney P. Smith III, MD; 900 Mohawk Street Ste E, Savannah, GA 31419; ssmithmd@complete.md

Manuscript Accepted: May 24, 2024