A study on effect of a novel total nutritional composition for repairing full-thickness skin defects in rats_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

HAN Shaofang ¹ , GAO Xuechu ^1,2 , ZHANG Yunwei ³ , LIANG Binjie ⁴ , QIAN Peipei ¹ , WANG Hongyu ⁵ , YANG Jiayue ^1,6 , YU Huaqing ¹ , ZHANG Yong ¹ ,  LIU Lingying ^1,2,6

1. Department of Nutrition, Fourth Medical Center, Chinese PLA General Hospital, Beijing, 100037, P. R. China;
2. School of Basic Medical Sciences, Inner Mongolia Medical University, Hohhot Inner Mongolia, 010107, P. R. China;
3. Department of Gastrointestinal Surgery, Xiamen Hong’ai Hospital, Xiamen Fujian, 361000, P. R. China;
4. Department of Orthopedics, Zhangzhou Third Hospital, Zhangzhou Fujian, 363000, P. R. China;
5. Department of Burns, Inner Mongolia Baogang Hospital, Baotou Inner Mongolia, 014010, P. R. China;
6. Basic Medical College, Hebei North University, Zhangjiakou Hebei, 075031, P. R. China;

Corresponding?author：

LIU Lingying, Email: liulingyingyisheng@163.com

Keywords：

Nutrients; protein; β-hydroxy-β-methylbutyrate; full-thickness skin defect; wound healing; rat

DOI：

10.7507/1002-1892.202601009

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Objective To investigate the effects of a novel total nutritional composition on the healing of full-thickness skin defects in rats. Methods Ninety SPF male Wistar rats aged 8-12 weeks were randomly divided into 5 groups, with 18 rats in each group: normal group (group A), model group (group B), equal-energy standard nutrition preparation group (group C), equal-protein component group (group D), and nutritional composition group (group E). Except group A, full-thickness skin defects of 1.5 cm in diameter were established on the back of rats in the other four groups. On the basis of conventional feeding, rats received intragastric administration of sterile water or corresponding nutritional preparations twice a day for 14 consecutive days. General wound appearance was observed and wound healing rate was calculated at 0, 7, 10, and 14 days after injury. Six rats per group were sacrificed at 7, 10, and 14 days after injury to collect wound tissues. HE and Masson trichrome staining were performed to observe histopathological changes. Immunohistochemical staining was used to detect CD31-positive microvessel density. Results At 7, 10, and 14 days after injury, wound healing rates in groups C, D, and E were significantly higher than those in group B, and group E was significantly higher than group D (P<0.05). No significant difference was detected between group C and group E at all time points (P>0.05). Histological results showed that group E had the least necrotic tissue, mildest inflammatory infiltration, richest neovascularization, widest re-epithelialization range, as well as the densest and most regularly arranged collagen deposition, with better repair effects than groups C and D. CD31 immunohistochemistry indicated that microvessel densities in groups B-E were significantly higher than that in group A (P<0.05). Microvessel density in groups C, D, and E was significantly higher than that in group B, and groups C and E were significantly higher than group D (P<0.05). There was no significant difference between group C and group E (P>0.05). Conclusion The novel total nutritional composition can relieve wound inflammation, promote collagen deposition and angiogenesis, and accelerate skin wound healing. It possesses better repair efficacy than equal-protein formula, comparable therapeutic effect with equal-energy nutritional preparation, and shows obvious advantages in early wound healing.

Citation： HAN Shaofang, GAO Xuechu, ZHANG Yunwei, LIANG Binjie, QIAN Peipei, WANG Hongyu, YANG Jiayue, YU Huaqing, ZHANG Yong, LIU Lingying. A study on effect of a novel total nutritional composition for repairing full-thickness skin defects in rats. Chinese Journal of Reparative and Reconstructive Surgery, 2026, 40(6): 964-973. doi: 10.7507/1002-1892.202601009 Copy

1.	Grada A, Phillips TJ. Nutrition and cutaneous wound healing. Clin Dermatol, 2022, 40(2): 103-113.
2.	Wilkinson HN, Hardman MJ. Wound healing: cellular mechanisms and pathological outcomes. Open Biol, 2020, 10(9): 200223. doi: 10.1098/rsob.200223.
3.	Ju M, Kim Y, Seo KW. Role of nutrition in wound healing and nutritional recommendations for promotion of wound healing: a narrative review. Annals of Clinical Nutrition and Metabolism, 2023, 15(3): 67-71.
4.	Posthauer ME, Dorner B, Collins N. Nutrition: a critical component of wound healing. Adv Skin Wound Care, 2010, 23(12): 560-572; quiz 573-564.
5.	中華醫學會腸外腸內營養學分會. 成人圍手術期營養支持指南. 中華外科雜志, 2016, 54(9): 641-657.
6.	中華醫學會腸外腸內營養學分會. 中國成人患者腸外腸內營養臨床應用指南 (2023版). 中華醫學雜志, 2023, 103(13): 946-974.
7.	Boirie Y, Dangin M, Gachon P, et al. Slow and fast dietary proteins differently modulate postprandial protein accretion. Proc Natl Acad Sci U S A, 1997, 94(26): 14930-14935.
8.	Rathmacher JA, Pitchford LM, Stout JR, et al. International society of sports nutrition position stand: β-hydroxy-β-methylbutyrate (HMB). J Int Soc Sports Nutr, 2025, 22(1): 2434734. doi: 10.1080/15502783.2024.2434734.
9.	Saeg F, Orazi R, Bowers GM, et al. Evidence-based nutritional interventions in wound care. Plast Reconstr Surg, 2021, 148(1): 226-238.
10.	Basiri R, Spicer MT, Levenson CW, et al. Nutritional supplementation concurrent with nutrition education accelerates the wound healing process in patients with diabetic foot ulcers. Biomedicines, 2020, 8(8): 263. doi: 10.3390/biomedicines8080263.
11.	Berger MM, Baines M, Raffoul W, et al. Trace element supplementation after major burns modulates antioxidant status and clinical course by way of increased tissue trace element concentrations. Am J Clin Nutr, 2007, 85(5): 1293-1300.
12.	Cao Q, Xu W, Chen X, et al. PRMT1-mediated arginine methylation promotes corneal epithelial wound healing via epigenetic regulation of anxa3. Invest Ophthalmol Vis Sci, 2025, 66(1): 22. doi: 10.1167/iovs.66.1.22.
13.	Daher GS, Choi KY, Wells JW, et al. A systematic review of oral nutritional supplement and wound healing. Ann Otol Rhinol Laryngol, 2022, 131(12): 1358-1368.
14.	Hill B, Mitchell A, Szydlowska A, et al. The role of nutrition in wound healing and implications for nursing practice. Br J Nurs, 2025, 34(4): S39-S42.
15.	彭曦, 孫勇. 燒傷創面修復中的代謝問題及營養策略. 中華燒傷與創面修復雜志, 2022, 38(8): 707-713.
16.	Seth I, Lim B, Cevik J, et al. Impact of nutrition on skin wound healing and aesthetic outcomes: A comprehensive narrative review. JPRAS Open, 2024, 39: 291-302.
17.	Basiri R, Spicer M, Levenson C, et al. Improving dietary intake of essential nutrients can ameliorate inflammation in patients with diabetic foot ulcers. Nutrients, 2022, 14(12): 2393. doi: 10.3390/nu14122393.
18.	Xin XY, Zhou J, Liu GG, et al. Anti-inflammatory activity of collagen peptide in vitro and its effect on improving ulcerative colitis. NPJ Sci Food, 2025, 9(1): 1. doi: 10.1038/s41538-024-00367-7.
19.	Kumazawa Y, Mizuno K, Taga Y. Collagen-derived hydroxyproline-containing cyclic dipeptides prevent photoaging-related inflammatory response in UVB-irradiated epidermal keratinocytes. Photochem Photobiol, 2025. doi: 10.1111/php.70026.
20.	Cacciatore S, Calvani R, Esposito I, et al. Emerging targets and treatments for sarcopenia: A narrative review. Nutrients, 2024, 16(19): 3271. doi: 10.3390/nu16193271.
21.	Badr G. Supplementation with undenatured whey protein during diabetes mellitus improves the healing and closure of diabetic wounds through the rescue of functional long-lived wound macrophages. Cell Physiol Biochem, 2012, 29(3-4): 571-582.
22.	Okamoto K, Takamura H, Nagayama T, et al. Usefulness of perioperative nutritional therapy with the glutamine/arginine/calcium β-hydroxy-β-methylbutyrate product in esophageal cancer surgery: A single-center retrospective study. Nutrients, 2024, 16(13): 2126. doi: 10.3390/nu16132126.
23.	Da Porto A, Miranda C, Brosolo G, et al. Nutritional supplementation on wound healing in diabetic foot: What is known and what is new? World J Diabetes, 2022, 13(11): 940-948.
24.	Tracy LE, Minasian RA, Caterson EJ. Extracellular matrix and dermal fibroblast function in the healing wound. Adv Wound Care (New Rochelle), 2016, 5(3): 119-136.
25.	Lin H, Zheng Z, Yuan J, et al. Collagen peptides derived from sipunculus nudus accelerate wound healing. Molecules, 2021, 26(5): 1385. doi: 10.3390/molecules26051385.
26.	Salvo J, Sandoval C. Role of copper nanoparticles in wound healing for chronic wounds: literature review. Burns Trauma, 2022, 10: tkab047. doi: 10.1093/burnst/tkab047.
27.	Lansdown AB, Mirastschijski U, Stubbs N, et al. Zinc in wound healing: theoretical, experimental, and clinical aspects. Wound Repair Regen, 2007, 15(1): 2-16.
28.	Erdem HA, Yal??n N, Kaya A, et al. Vitabiotic: An alternative approach to diabetic foot. Wound Repair Regen, 2024, 32(6): 890-894.
29.	Li N, Lan J, Yang J, et al. Whole milk protein powder separated by low-temperature nanofiltration membrane administration alleviates sepsis-induced myopathy. Nutr Metab (Lond), 2024, 21(1): 85. doi: 10.1186/s12986-024-00862-4.
30.	Das A, Ash D, Fouda AY, et al. Cysteine oxidation of copper transporter CTR1 drives VEGFR2 signalling and angiogenesis. Nat Cell Biol, 2022, 24(1): 35-50.

1. Grada A, Phillips TJ. Nutrition and cutaneous wound healing. Clin Dermatol, 2022, 40(2): 103-113.
2. Wilkinson HN, Hardman MJ. Wound healing: cellular mechanisms and pathological outcomes. Open Biol, 2020, 10(9): 200223. doi: 10.1098/rsob.200223.
3. Ju M, Kim Y, Seo KW. Role of nutrition in wound healing and nutritional recommendations for promotion of wound healing: a narrative review. Annals of Clinical Nutrition and Metabolism, 2023, 15(3): 67-71.
4. Posthauer ME, Dorner B, Collins N. Nutrition: a critical component of wound healing. Adv Skin Wound Care, 2010, 23(12): 560-572; quiz 573-564.
5. 中華醫學會腸外腸內營養學分會. 成人圍手術期營養支持指南. 中華外科雜志, 2016, 54(9): 641-657.
6. 中華醫學會腸外腸內營養學分會. 中國成人患者腸外腸內營養臨床應用指南 (2023版). 中華醫學雜志, 2023, 103(13): 946-974.
7. Boirie Y, Dangin M, Gachon P, et al. Slow and fast dietary proteins differently modulate postprandial protein accretion. Proc Natl Acad Sci U S A, 1997, 94(26): 14930-14935.
8. Rathmacher JA, Pitchford LM, Stout JR, et al. International society of sports nutrition position stand: β-hydroxy-β-methylbutyrate (HMB). J Int Soc Sports Nutr, 2025, 22(1): 2434734. doi: 10.1080/15502783.2024.2434734.
9. Saeg F, Orazi R, Bowers GM, et al. Evidence-based nutritional interventions in wound care. Plast Reconstr Surg, 2021, 148(1): 226-238.
10. Basiri R, Spicer MT, Levenson CW, et al. Nutritional supplementation concurrent with nutrition education accelerates the wound healing process in patients with diabetic foot ulcers. Biomedicines, 2020, 8(8): 263. doi: 10.3390/biomedicines8080263.
11. Berger MM, Baines M, Raffoul W, et al. Trace element supplementation after major burns modulates antioxidant status and clinical course by way of increased tissue trace element concentrations. Am J Clin Nutr, 2007, 85(5): 1293-1300.
12. Cao Q, Xu W, Chen X, et al. PRMT1-mediated arginine methylation promotes corneal epithelial wound healing via epigenetic regulation of anxa3. Invest Ophthalmol Vis Sci, 2025, 66(1): 22. doi: 10.1167/iovs.66.1.22.
13. Daher GS, Choi KY, Wells JW, et al. A systematic review of oral nutritional supplement and wound healing. Ann Otol Rhinol Laryngol, 2022, 131(12): 1358-1368.
14. Hill B, Mitchell A, Szydlowska A, et al. The role of nutrition in wound healing and implications for nursing practice. Br J Nurs, 2025, 34(4): S39-S42.
15. 彭曦, 孫勇. 燒傷創面修復中的代謝問題及營養策略. 中華燒傷與創面修復雜志, 2022, 38(8): 707-713.
16. Seth I, Lim B, Cevik J, et al. Impact of nutrition on skin wound healing and aesthetic outcomes: A comprehensive narrative review. JPRAS Open, 2024, 39: 291-302.
17. Basiri R, Spicer M, Levenson C, et al. Improving dietary intake of essential nutrients can ameliorate inflammation in patients with diabetic foot ulcers. Nutrients, 2022, 14(12): 2393. doi: 10.3390/nu14122393.
18. Xin XY, Zhou J, Liu GG, et al. Anti-inflammatory activity of collagen peptide in vitro and its effect on improving ulcerative colitis. NPJ Sci Food, 2025, 9(1): 1. doi: 10.1038/s41538-024-00367-7.
19. Kumazawa Y, Mizuno K, Taga Y. Collagen-derived hydroxyproline-containing cyclic dipeptides prevent photoaging-related inflammatory response in UVB-irradiated epidermal keratinocytes. Photochem Photobiol, 2025. doi: 10.1111/php.70026.
20. Cacciatore S, Calvani R, Esposito I, et al. Emerging targets and treatments for sarcopenia: A narrative review. Nutrients, 2024, 16(19): 3271. doi: 10.3390/nu16193271.
21. Badr G. Supplementation with undenatured whey protein during diabetes mellitus improves the healing and closure of diabetic wounds through the rescue of functional long-lived wound macrophages. Cell Physiol Biochem, 2012, 29(3-4): 571-582.
22. Okamoto K, Takamura H, Nagayama T, et al. Usefulness of perioperative nutritional therapy with the glutamine/arginine/calcium β-hydroxy-β-methylbutyrate product in esophageal cancer surgery: A single-center retrospective study. Nutrients, 2024, 16(13): 2126. doi: 10.3390/nu16132126.
23. Da Porto A, Miranda C, Brosolo G, et al. Nutritional supplementation on wound healing in diabetic foot: What is known and what is new? World J Diabetes, 2022, 13(11): 940-948.
24. Tracy LE, Minasian RA, Caterson EJ. Extracellular matrix and dermal fibroblast function in the healing wound. Adv Wound Care (New Rochelle), 2016, 5(3): 119-136.
25. Lin H, Zheng Z, Yuan J, et al. Collagen peptides derived from sipunculus nudus accelerate wound healing. Molecules, 2021, 26(5): 1385. doi: 10.3390/molecules26051385.
26. Salvo J, Sandoval C. Role of copper nanoparticles in wound healing for chronic wounds: literature review. Burns Trauma, 2022, 10: tkab047. doi: 10.1093/burnst/tkab047.
27. Lansdown AB, Mirastschijski U, Stubbs N, et al. Zinc in wound healing: theoretical, experimental, and clinical aspects. Wound Repair Regen, 2007, 15(1): 2-16.
28. Erdem HA, Yal??n N, Kaya A, et al. Vitabiotic: An alternative approach to diabetic foot. Wound Repair Regen, 2024, 32(6): 890-894.
29. Li N, Lan J, Yang J, et al. Whole milk protein powder separated by low-temperature nanofiltration membrane administration alleviates sepsis-induced myopathy. Nutr Metab (Lond), 2024, 21(1): 85. doi: 10.1186/s12986-024-00862-4.
30. Das A, Ash D, Fouda AY, et al. Cysteine oxidation of copper transporter CTR1 drives VEGFR2 signalling and angiogenesis. Nat Cell Biol, 2022, 24(1): 35-50.

Chinese Journal of Reparative and Reconstructive Surgery

A study on effect of a novel total nutritional composition for repairing full-thickness skin defects in rats

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