Challenging Cases: Using Hydrolyzed Type 1 Collagen Powder and Antimicrobial Cleanser in Neonates and Older Children

This month’s article continues the thread of challenging and interesting neonatal and pediatric cases. It provides an overview of the approach used to treat such cases while emphasizing the feasibility of using 2 new products (in pediatric wound care): an antimicrobial skin and wound cleanser as well as type 1 hydrolyzed collagen powder. 

A 2-month-old infant presented to the emergency department with hemorrhagic shock secondary to a rapidly enlarging lower extremity vascular lesion. The lower extremity soft tissue abnormality had been noted soon after birth and was being observed for progressive growth. The patient’s parents noted spontaneous rupture of the lesion with significant bleeding, which prompted this presentation. Upon admission to the hospital and after hemodynamic stabilization, a lesion biopsy was performed. The patient was diagnosed with fibrosarcoma, and chemotherapy was begun. Although initial chemotherapy was well tolerated, the protocol was changed when genetic test results encouraged the initiation of targeted therapy. The patient’s immediate clinical state at presentation to the emergency department and medical floor required resuscitation with a red blood cell transfusion, platelets, and granulocyte growth factors because thrombocytopenia and neutropenia were also present.   

Once hemodynamically stable and receiving the targeted regimen, the patient was discharged home. His very large, open fibrosarcoma was managed by plastics with topical antibiotic ointment, petrolatum-impregnated gauze, and  Kerlix gauze (Covidien, Dublin, Ireland). The mass was located on the medial interphase between the ankle and foot, at the joint area; therefore, the patient was given a plastic foot-supporting prosthesis to avoid foot drop. The author was consulted to help with care approximately 3 to 4 weeks after discharge (Figure 1). 

The tissue mass was receding, yet the open wound had not made progress toward healing; it was still large, almost fungating, with an unpleasant smell, thin exudate, no granulation tissue, and jagged base. The parents were afraid to clean the area well and only gently wiped the surface. In addition, the patient had tracheomalacia and poor tolerance for oral feeding. The author was concerned about the adequacy of nutrition and the amino acids status for optimal healing. The patient’s diet was changed to calorie- and protein-enriched formula to optimize nutrition. Wound management was changed to an antimicrobial skin and wound cleanser (BIAKŌS; Sanara MedTech, Fort Worth, TX) with each dressing change (every 3 days) and hydrophobic dialkylcarbamoyl chloride outer dressing to decrease likely colonization between cleaning sessions and provide physical coverage for the next 2 weeks. The solution was tested on a small area for 10 minutes before full application. 

At the next appointment, 8 days later, the wound was smaller, clean, and drier. The patient’s mother was excited that the foul smell was eliminated. Unfortunately, granulation tissue growth was not appreciated. Hydrolyzed collagen powder (Hycol; Sanara MedTech, Fort Worth, TX) was added to the regimen. The parents were taught to cleanse the wound first by applying the antimicrobial cleanser to the wound directly, then moistening a gauze with the cleanser and allowing it to stay on the wound for 2 to 3 minutes, after which gently but thoroughly cleaning the outside wound bed with water and allowing it to dry. The second step was to apply hydrolyzed collagen powder, cover with a hydrocolloid polyester contact mesh layer (UrgoTul; Urgo Medical North America, Fort Worth, TX), and finally outer Kerlix (Figure 2). This was repeated every 4 to 5 days.  

When the patient returned 10 days later, healthy granulation tissue was visible. In addition, areas of epithelial islands were developing (Figure 3 and Figure 4). The wound healed completely within 6 weeks of the management change (Figure 5). 

A 2-day-old, ex 33-week neonate with intrauterine growth retardation sustained stage 4 extravasation (Figure 6). The wound required debridement as slough was prevalent (Figure 7). An enzymatic debrider (Collagenase Santyl; Smith & Nephew, Fort Worth, TX) covered by methylene blue/gentian violet impregnated foam (Hydrofera Blue; Hydrofera, Manchester, CT) and an outer silicon dressing were applied. Collagenase was applied daily. Prior to each new application, the antimicrobial skin and wound cleanser was sprayed on the wound bed and a cleanser-soaked gauze was used for gentle mechanical cleaning. Noticeable improvement was seen by the third day, and the wound bed was clean by day 6. Hydrolyzed collagen powder was applied to the wound bed, covered by a small piece of perforated wound contact layer (Mepitel; Mölnlycke, Gothenburg, Sweden) every 3 days (Figure 8 and Figure 9). Collagen was incorporated into the wound within hours. The wound healed completely in 2.5 weeks (Figure 10).

The antimicrobial skin and wound cleanser used in these patients is a relatively new addition to the author’s pediatric wound cleaning regimen. Most units use normal saline and sterile or tap water to cleanse. Some have incorporated cleansers with hypochlorous acid. Cytotoxicity and percutaneous systemic absorption with potential worrisome side effects shape neonatal/pediatric practice and lead to cautious use of cleansers approved for use in adults. Common antiseptic cleansers include alcohol, iodine, chlorhexidine gluconate, silver, acetic acid, and hydrogen peroxide. All have potential systemic and topical cytotoxic side effects. A clean wound is at the helm of wound healing. Some wounds may need simple, superficial cleaning, whereas others require more aggressive debriding agents in combination with cleaning. 

The wound in case 1 was unique because the patient’s parents were caring for the wound at home. The wound was large, fungating, foul-smelling, and covered in thin exudate. The wound required both effective debridement and cleaning; the challenge was to find a product to ensure biofilm elimination with minimal scrubbing. The antimicrobial skin and wound cleanser ingredients enhanced debris and biofilm removal with the surfactant addition (promoting extrapolymeric substance disruption) and antimicrobial coverage with nonirritating polyhexamethylene biguanide (PHMB). Studies have shown this solution to be effective in killing free-floating microbes, immature and mature bacterial biofilms such as methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, and fungal biofilms such as Candida albicans.^1–4 PHMB is known to be active against both planktonic and sessile bacteria found in biofilm. A cationic polymer, this broad antimicrobial interacts with negatively charged phospholipids in the bacterial membrane, leading to instability and integrity disruption.^1–4 Extrapolymeric substance disruption and enhanced removal were noted with PHMB in adult studies.^5,6  

Unlike its cousin, chlorhexidine gluconate, PHMB does not produce systemic toxic metabolites. The chemical structure of PHMB is similar to that of antimicrobial peptides produced by keratinocytes and neutrophils inside the wound. PHMB has been found to be nonirritating compared to previously mentioned antiseptics or antimicrobials; it is well tolerated on mucous membranes, noncytotoxic to wound epithelial cells, and stimulates reepithelialization while providing antimicrobial coverage.^1–4 In wounds with a hyper-inflammatory milieu, it decreases metalloproteases and inflammation. The literature recommends the use of surfactants and pH-balanced skin cleansers.⁷ 

The addition of surfactant allows micelle formation, enveloping exudate and facilitating easier debridement, and thus decreasing inflammation further. The nonionic surfactant, poloxamer 407, is a triblock copolymer consisting of a central hydrophobic block (polypropylene glycol); 2 hydrophilic blocks of polyethylene glycol decrease surface tension and increase the solubility of vicinal diols due to the amphiphilic competency.⁸ Another component of the solution, vicinal diols, represent moisturizing humectants, with antimicrobial and odor-reducing functions. In case 1, the wound was vascular and bled easily with any trauma. Humectants envelop the wound, decreasing drying and trauma potential. Maintenance of mildly acidic to neutral pH is advantageous to pediatric and especially newborn skin because babies are born with more alkalotic pH. Acid mantle preservation is an important antimicrobial defense mechanism in addition to support of skin integrity. The pH of the solution is 5.5, which is within the suggested target range. It is known that the defense and healing mechanisms of the skin function best at a physiologic acid mantle, with pH between 4.5 and 6. The enzymes in the upper epidermis are optimized to function at a pH of 5.6.⁹ Newborns, especially preterm ones, have slightly basic skin pH. Therefore, applying an acidic cleanser optimizes acid mantle. BIAKŌS solution is isotonic, which is especially important in a child with a very vascular wound or preterm epithelium to ensure nonpainful application and prevent cellular dehydration or shrinkage. Finally, the addition of ethylene diamine that tetraacetic acid sodium salts provides further supports mildly acidic pH. 

Collagen accounts for 30% of the protein of humans and 77% of the dry weight of skin. Collagen molecules are composed of 3 polypeptide chains that are aligned in a parallel manner and coiled in a left-handed helix.^10–12 Types 1, 2, 3, 5, and 11 collagen have fibrillary quaternary structure. Type 1 collagen is the most abundant type in animals and most often used in medicine. Hydrolyzed type 1 bovine collagen was chosen to enhance the proliferative stage in the 2 cases presented here, 1 of an immunocompromised infant and the other, a preterm neonate. 

Amino acid and protein intake are paramount for healing and collagen formation. Providing hydrolyzed collagen expedited the healing reported in this article. Natural collagens can be prepared in many ways but overall belong to 2 categories: decellularized matrix that maintains original tissue properties and extracellular matrix (ECM) structure, and a collagen scaffold prepared by extraction, purification, or polymerization.^10–13 Collagen-based scaffolds involve processing collagen with other molecules or dissolving to change the preparation. Sponges, powders, amorphous hydrogels, films, membranes, various collagen-impregnated wound dressings, and skin substitutes are available. Significant clinical and laboratory data support its use, enhancing all stages of wound healing. Ease of application in challenging spaces and complete spread over the wound bed led to the incorporation of type 1 activated hydrolyzed collagen powder into the author’s practice. 

The literature on adult patients has reported improved outcomes with hydrolyzed collagen, citing product versatility, faster healing rates due to immediate bioavailability, and smaller molecular sizes leading to expedited cellular matrix incorporation and robust fibroblast response.^10–13 In the current case reports, the powder diminished the inflammatory process and decreased matrix metalloproteases destruction of the ECM. Collagen enhanced the proliferative stage, contributing collagen peptides, stimulating fibroblasts, and promoting ECM deposition. In both cases, collagen addition was crucial to successful healing. The patient in case 1 did not have optimal nutrition status, limiting amino acids availability, in addition to strong medications that were likely suppressing healing. The patient in case 2 was a preterm neonate with inadequate amino acids and other nutrients’ storage. Both cases healed well and fast compared to the historical control of these types of wounds. The product was easy to apply by all caregivers, including parents at home.

From experience, the author would recommend considering both the cleanser and the hydrolyzed collagen powder in wounds requiring significant cleansing, debridement, and enhancement of ECM growth.

Dr. Boyar is director of Neonatal Wound Services, Cohen Children’s Medical Center of New York, New Hyde Park, and assistant professor of Pediatrics, Zucker School of Medicine, Hofstra/Northwell, Hempstead, NY. All photos provided are with the consent of the patients’ parents. This article was not subject to the Wound Management & Prevention peer-review process.