Cutaneous wound healing after treatment with plant-derived human recombinant collagen flowable gel
Open accessAbstract
Chronic wounds, particularly diabetic ulcers, represent a main public health concern with significant costs. Ulcers often harbor an additional obstacle in the form of tunneled or undermined wounds, requiring treatments that can reach the entire wound tunnel, because bioengineered grafts are typically available only in a sheet form. While collagen is considered a suitable biodegradable scaffold material, it is usually extracted from animal and human cadaveric sources, and accompanied by potential allergic and infectious risks. The purpose of this study was to test the performance of a flowable gel made of human recombinant type I collagen (rhCollagen) produced in transgenic tobacco plants, indicated for the treatment of acute, chronic, and tunneled wounds. The performance of the rhCollagen flowable gel was tested in an acute full-thickness cutaneous wound-healing rat model and compared to saline treatment and two commercial flowable gel control products made of bovine collagen and cadaver human skin collagen. When compared to the three control groups, the rhCollagen-based gel accelerated wound closure and triggered a significant jumpstart to the healing process, accompanied by enhanced re-epithelialization. In a cutaneous full-thickness wound pig model, the rhCollagen-based flowable gel induced accelerated wound healing compared to a commercial product made of bovine tendon collagen. By day 21 post-treatment, 95% wound closure was observed with the rhCollagen product compared to 68% closure in wounds treated with the reference product. Moreover, rhCollagen treatment induced an early angiogenic response and induced a significantly lower inflammatory response than in the control group. In summary, rhCollagen flowable gel proved to be efficacious in animal wound models and is expected to be capable of reducing the healing time of human wounds.
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Plant-derived rhCollagen has shown no antigenic or immunogenic responses in human CD4+ T cells, in contrast to bovine collagen, which is known to trigger immune reactions.
“Notably, plant-derived rhCollagen has shown no antigenic or immunogenic responses in human CD4+ T cells, in contrast to bovine collagen, which is known to trigger immune reactions [40].”
From Biomaterials in Postoperative Adhesion Barriers and Uterine Tissue Engineering (2025) · cites this paper as [40]
The Introduction says animal-derived collagen can provoke immune responses, and the Discussion reports less inflammation with rhCollagen than with bovine collagen in pig wounds. The paper does not report testing human CD4+ T cells or establish that rhCollagen produces no antigenic or immunogenic response in those cells. (LLM, conf=0.88)
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Tonnesen, M. G., Feng, X., & Clark, R. A. F. (2000) · Journal of Investigative Dermatology Symposium Proceedings · doi:10.1046/j.1087-0024.2000.00014.x · Cited by 1,463 · see citing works
Matricellular proteins as modulators of wound healing and the foreign body response
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Research works printed but not linked: 3
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Fertala, A. (2020) · Bioengineering · doi:10.3390/bioengineering7040155 · Cited by 109 · see citing works
Biomaterials in Postoperative Adhesion Barriers and Uterine Tissue Engineering
Fazel Anvari-Yazdi, A., Badea, I., & Chen, X. (2025) · Gels · doi:10.3390/gels11060441 · Cited by 20 · see citing works
- Authors
- Shilo, S., Roth, S., Amzel, T., Harel-Adar, T., Tamir, E., Grynspan, F., & Shoseyov, O.
- Affiliations
- CollPlant Ltd., Ness-Ziona, Israel.
- Maccabi Healthcare Services (IL)
- Hebrew University of Jerusalem (IL)
- Corresponding author
- Shilo, Shani
- Venue
- Tissue Engineering Part A
- Publisher
- SAGE Publications
- Published
- 2013-07
- Volume
- 19
- Issue
- 13-14
- Pages
- 1519-1526
- ISSN
- 1937-3341 (ISSN-L)
- 1937-335X
- PMC
- PMC3665308
- OpenAlex
- W2032307986
- Cited by
- 64
- References
- 2
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 5 · 2019: 8 · 2018: 5 · 2017: 4 · 2016: 5 · 2015: 5 · 2014: 5 · 2013: 3
- FWCI
- 4.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Tissue Engineering Part A (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Physical Sciences › Materials Science › Biomaterials › Collagen: Extraction and Characterization
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- skin wound healing, diabetic ulcers, re-epithelialization, angiogenesis, inflammation, bovine collagen, biodegradable scaffolds, wound dressings
- MeSH terms
- Animals, Cattle, Collagen, Humans, Plants, Recombinant Proteins, Skin, Swine, Wound Healing, Rats
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