Wound Healing 

The skin is the largest organ of the human body and serves as the first line of defense, maintaining internal equilibrium while protecting against external threats such as burns, cuts, toxic agents, and infectious materials. Due to this critical role, the skin is highly susceptible to injury. Wound healing is a complex physiological process and unlike fetal skin, which has the remarkable ability to heal without scarring, adult skin typically repairs itself with scar formation (Alberts et al., 2025; Gomes et al., 2025). Collagen is the primary extracellular matrix (ECM) protein, and it increases progressively during gestation, resulting in the formation of greater crosslinking and larger fiber structures. While type I collagen is the dominant form in adult and fetal skin, fetal skin also includes higher proportions of collagen types III and V (Gomes et al., 2025). In recent years, the inherent healing properties of collagen have inspired the development of a wide range of collagen-based wound care technologies, including hydrogels, films, foams, and dressings (Alberts et al., 2025). Collagen-based supplements have also gained significant interest, including both hydrolyzed and non-hydrolyzed forms to support faster and more efficient healing responses (Benito-Martínez et al., 2025). This edition highlights four studies that investigate the effectiveness of collagen-based therapies in tissue regeneration and wound healing. 

The effect of a hydrolyzed collagen-based supplement on wound healing in patients with burn: A randomized double-blind pilot clinical trial 

Burns are severe traumatic events that often necessitate intensive care, prolonged hospitalization, and extensive rehabilitation. Tissue damage from burns can lead to substantial pain, compromised immunity, increased infection risk, and scaring, requiring effective wound care strategies. In addition to topical treatments, nutritional support, particularly collagen-based supplements, has been explored to help meet metabolic demands and mitigate burn-induced hypermetabolism. This randomized, double-blind, placebo-controlled pilot trial evaluated the effects of an oral, low-cost collagen-based supplement on wound healing in 31 men (aged 18-16 years) with 20-30% total body surface area burns. Participants received either 1000 kcal of the collagen supplement or an isocaloric placebo for four weeks, with serum pre-albumin, wound healing rate, hospital stay length, and anthropometries assessed at baseline and weeks two and four. By weeks two and four, serum pre-albumin levels and changes in pre-albumin concentration were significantly higher in the collagen group compared to the control group. The hazard ratio of wound healing was also significantly higher in the collagen group, while hospital stay was clinically lower but not statistically significant, compared to the control group. No significant differences were observed in weight, body mass index, or dietary intakes between the two groups. Collectively, these findings support the effect of hydrolyzed collagen supplementation in enhancing wound healing, improving circulating pre-albumin concentrations, and clinically reducing hospital stays in patients with moderate burns.  

Access to the study: https://pubmed.ncbi.nlm.nih.gov/31859087/  

Reference: Bagheri Miyab, K., Alipoor, E., Vaghardoost, R., Saberi Isfeedvajani, M., Yaseri, M., Djafarian, K., & Hosseinzadeh-Attar, M. J. (2020). The effect of a hydrolyzed collagen-based supplement on wound healing in patients with burn: A randomized double-blind pilot clinical trial. Burns : journal of the International Society for Burn Injuries, 46(1), 156–163. https://doi.org/10.1016/j.burns.2019.02.015   

Effects of hydrolyzed collagen alone or in combination with fish oil on the gut microbiome in patients with major burns 

Major burns are among the most severe forms of traumas and physiological stress, often accompanied by pronounced protein and lipid catabolism, inflammation, and increased susceptibility to infection. Although burn wound care has advanced, infection remains a persistent challenge in thermal injuries. As gut microbiota composition is influenced by factors such as nutrition, trauma, and infection, disruptions in this balance can influence immune function. Consequently, severe burns have been linked to gut microbiome dysbiosis, while a healthy microbiome may act as a barrier, preventing opportunistic infections. This randomized, double-blind clinical trial investigated the effects of hydrolyzed collagen, alone or in combination with fish oil, on specific gut microbiome species in patients with major burns. Fifty-seven adults (aged 18-60 years) with 20-45% total body surface area burns were randomized to one of three groups for two weeks: 1) 40 g hydrolyzed collagen + 10 ml sunflower oil; 2) 40 g hydrolyzed collagen + 10 ml fish oil; 3) placebo, administered twice daily. Quantification by real-time quantitative polymerase chain reaction showed a significant reduction in the mean concentration of Bifidobacterium in the control and collagen groups compared to baseline, with no significant change observed in the collagen plus omega-3 group. The Firmicutes to Bacteroidetes ratio decreased significantly in the collagen group compared to baseline, with no meaningful changes in Lactobacillus, Enterobacteriaceae, and Faecalibacterium prausnitzii between or within groups. Altogether, these results suggest that two weeks of collagen supplementation combined with omega-3 fatty acids in patients with major burns did not significantly affect the concentration of gut bacteria, but it did prevent the significant reduction in Bifidobacterium seen in the control and collagen + sunflower oil groups. Future studies should focus on these nutritional intervention’s effects in relation to clinical outcomes of burns.  

Access to the study: https://pubmed.ncbi.nlm.nih.gov/38114377/  

Reference: Salehi, S., Hosseinzadeh-Attar, M. J., Alipoor, E., Dahmardehei, M., Yaseri, M., Emami, M. R., & Siadat, S. D. (2024). Effects of hydrolyzed collagen alone or in combination with fish oil on the gut microbiome in patients with major burns. Burns : journal of the International Society for Burn Injuries, 50(2), 444–453. https://doi.org/10.1016/j.burns.2023.08.017   

Assessing New Collagen Therapies for Wound Healing: A Murine Model Approach 

The skin is constantly exposed to injury while maintaining body’s homeostasis, regulating its temperature, and protecting from external harms like chemical, physical, and biological agents. Wound healing restores the skin’s functional and structural integrity, involving consecutive cellular and molecular events. Collagen therapies have emerged as innovative interventions to support regeneration and strength of the ECM. This study evaluated the efficacy of two new collagen-based products (hydrolyzed and non-hydrolyzed) with commercial products for wound repair in a murine model of cutaneous healing. Seventy-two female Wistar rats were used, in which circular excisional defects were generated, and were randomly assigned to one of six groups: 1) control (no treatment); 2) SD-C (semi-denatured type I bovine collagen); 3) Catrix (bovine cartilage collagen); 4) Hy-C (hydrolyzed bovine dermal collagen); 4) N-C (native type I bovine collagen); and 5) Helix3-CP (native type I, non-hydrolyzed bovine collagen particles). Wound closure and morphological, histological, and immunohistochemical changes were assessed at short term (seven days) and long term (18 days). After seven days, open areas and epithelialization were similar among groups; however, significance was observed in the differences in contraction between the control and the new collagen (N-C and Helix3-CP) groups. Untreated rats demonstrated a more profound granulation tissue with higher inflammatory cell numbers and disorganized ECM with type III collagen deposition. After 18 days, animals in the Hy-C and N-C groups exhibited accelerated wound closure, increased epithelialization, and a more organized granulation tissue. Overall, these results suggest that local administration of both hydrolyzed and non-hydrolyzed collagen may enhance the reparative process and accelerate wound closure compared with untreated wounds.       

Access to the study: https://pubmed.ncbi.nlm.nih.gov/40258681/  

Reference: Benito-Martínez, S., Pérez-Köhler, B., Rodríguez, M., Rivas-Santos, C., María Izco, J., Recalde, J. I., & Pascual, G. (2025). Assessing New Collagen Therapies for Wound Healing: A Murine Model Approach. International wound journal, 22(4), e70589. https://doi.org/10.1111/iwj.70589  

Hydrolyzed Versus Native Collagen in Management of Acute Surgical Wounds: A Literature Review 

Collagen is essential to the wound-healing process, as it is naturally broken down into collagen bioactive fragments that help initiate tissue repair. Hydrolyzed collagen provides these fragments in a readily available form, offering a “head-start” to wound healing. However, consolidated evidence supporting the clinical benefits of hydrolyzed collagen in the healing process, particularly acute surgical wound management, is still lacking. To address this gap, this literature review examined PubMed publications from 2018 to 2023 to identify research evaluating hydrolyzed collagen benefits in acute wound care. Fifteen relevant articles were retrieved, collectively demonstrating the numerous advantages of using hydrolyzed collagen over native collagen, specifically its higher solubility, lower molecular weight, and better bioavailability, all of which facilitate a faster and more efficient healing response. Reported outcomes included accelerated epithelialization, improved wound closure, reduced inflammation, enhanced cellular proliferation and migration, and increased tensile strength at the wound site. Several studies also reported reduced postoperative complications, such as reduced rates of surgical site infections. Overall, these findings support the value of hydrolyzed collagen as a promising and effective tool for acute surgical wound management, while also highlighting the need for larger, high-quality clinical studies to strengthen the evidence base.  

Access to the study: https://www.gavinpublishers.com/article/view/hydrolyzed-versus-native-collagen-in-management-of-acute-surgical-wounds-a-literature-review  

Reference: Tucker King, C. S., Lambert, D. M., Dieter, S., & Sims, B. R. (2024). Hydrolyzed versus native collagen in management of acute surgical wounds: A literature review. Journal of Surgery, 9(4). https://doi.org/10.29011/2575-9760.11025  

Bottom Line 

Collagen-based interventions continue to demonstrate meaningful potential in supporting wound repair across range of applications from surgical wounds to burn injuries. Evidence from recent studies highlights improvements in healing dynamics, epithelialization, inflammation, and tissue regeneration with both hydrolyzed and non-hydrolyzed collagen formulations. While findings are promising, additional well-designed clinical trials are needed to better define collagen’s therapeutic value and optimize its use in wound management.  

References 

Alberts, A., Bratu, A. G., Niculescu, A. G., & Grumezescu, A. M. (2025). Collagen-Based Wound Dressings: Innovations, Mechanisms, and Clinical Applications. Gels (Basel, Switzerland), 11(4), 271. https://doi.org/10.3390/gels11040271.  

Benito-Martínez, S., Pérez-Köhler, B., Rodríguez, M., Rivas-Santos, C., María Izco, J., Recalde, J. I., & Pascual, G. (2025). Assessing New Collagen Therapies for Wound Healing: A Murine Model Approach. International wound journal, 22(4), e70589. https://doi.org/10.1111/iwj.70589.  

Gomes, M. L. N. P., Krijnen, P. A. J., Middelkoop, E., Niessen, H. W. M., & Boekema, B. K. H. L. (2025). Fetal Skin Wound Healing: Key Extracellular Matrix Components and Regulators in Scarless Healing. The Journal of investigative dermatology, 145(2), 280–302. https://doi.org/10.1016/j.jid.2024.05.027.