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Exogenous hyaluronic acid induces accelerated re-epithelialization and altered protein expression in adult human skin wounds in vivo
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background

Hyaluronic acid, a large glycosaminoglycan involved in proliferation, migration, and tissue repair, is suggested to play an important role in ideal scarless fetal wound healing. This study aimed to investigate the effect of exogenous hyaluronic acid intradermal during deep dermal wound healing. Study parameters were erythema, re-epithelialization, and protein expression examined by using a previously described, minimally invasive in vivo human wound model in combination with tissue viability imaging, histology, and proteomics.

Methods

Standardized deep dermal wounds were created in the ventral forearm in ten healthy volunteers using blood collection lancets. The wound sites were injected with hyaluronic acid or saline solution, prior to wounding, or were left untreated. To quantify changes in red blood cell concentration as a measurement of inflammation, the study sites were photographed daily for two weeks using a tissue viability imaging system. At 24 hours and after 14 days, biopsy specimens were taken for histology and proteomics analysis.

Results

The inflammatory response was not affected by the injection of hyaluronic acid, as measured by tissue viability imaging. Hyaluronic acid significantly induced (p < 0.05) accelerated reepithelialization at 24 hours, and wounds treated with hyaluronic acid showed an altered protein expression.

Conclusion

The results from the present study are in concordance with  previous in vitro findings and suggest that exogenous hyaluronic acid has a  positive effect on the healing process of cutaneous wounds. We conclude that hyaluronic acid injected intradermally induces accelerated re-epithelialization and alters protein expression in vivo in human deep dermal skin wounds.

Keyword [en]
Hyaluronic acid, hyaluronan, hyaluronate, Amniotic fluid, Wound healing, Human wound model, In vivo, Tissue viability imaging, Protein expression, proteomics
National Category
Medical Biotechnology Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-115593OAI: oai:DiVA.org:liu-115593DiVA: diva2:795852
Available from: 2015-03-17 Created: 2015-03-17 Last updated: 2015-03-17Bibliographically approved
In thesis
1. Guided Regeneration of the Human Skin: in vitro and in vivo studies
Open this publication in new window or tab >>Guided Regeneration of the Human Skin: in vitro and in vivo studies
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Every day and in all parts of the world, humans experience different grades of wounding and tissue loss of the skin, thus initiating one of the most complex biological processes. Acute and chronic wounds, as well as the additional problem of skin scarring, involve not only great suffering for the patient but also extensive health care costs for the society. Although the wound-healing process is a wellstudied field much knowledge must be gained to unlock the door to regenerative pathways in humans.

Epidermis heals by complete regeneration, but dermal and full thickness injuries heal with fibrosis and scar formation. In Papers I and II, we studied whether dermal scarring could be turned into regeneration by using two different types of threedimensional dermal scaffolds. In Paper I, we studied a solid scaffold made of poly(urethane urea), initially in vitro then followed by in vivo studies. In Paper II, we intradermally injected a liquid three-dimensional scaffold consisting of porous gelatin spheres in human healthy volunteers. Both materials showed ingrowth of functional fibroblasts and blood vessels and appeared to stimulate regeneration while slowly degrading. This finding could be of significant clinical importance, for example in burn wound care or after cancer surgery.

In Papers III and IV, we wanted to study the effects of amniotic fluid and hyaluronic acid on adult wound healing, because early fetal wounds re-epithelialize rapidly and naturally heal dermis by regeneration without the need of a dermal scaffold. Amniotic fluid, naturally rich in hyaluronic acid, induced an accelerated reepithelialization of adult human wounds in vitro, and hyaluronic acid seemed to be important for this effect. Stimulation with exogenous hyaluronic acid in vivo induced accelerated re-epithelialization and an altered protein expression in healthy human volunteers. The inflammatory phase of wound healing, as measured by tissue viability imaging, was not affected by hyaluronic acid. Elucidating the effects of amniotic fluid and hyaluronic acid on the wound-healing process may allow improved treatment of wounds with impaired healing.

Studies on finding new dermal scaffolds and studies on the positive effect of amniotic fluid or hyaluronic acid on the wound-healing process are two different ways of gaining insight that may lead to regeneration and improved wound healing for the patient.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2015. 95 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1450
National Category
Medical Bioscience Cell Biology
Identifiers
urn:nbn:se:liu:diva-115598 (URN)10.3384/diss.diva-115598 (DOI)978-91-7519-114-0 (ISBN)
Public defence
2015-04-20, Berzeliussalen, Campus US, Linköping, 09:00 (Swedish)
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Supervisors
Available from: 2015-03-17 Created: 2015-03-17 Last updated: 2015-03-17Bibliographically approved

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Nyman, ErikaHenricson, JoakimRakar, JonathanOlausson, PatrikGhafouri, BijarAnderson, ChrisKratz, Gunnar

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Nyman, ErikaHenricson, JoakimRakar, JonathanOlausson, PatrikGhafouri, BijarAnderson, ChrisKratz, Gunnar
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Division of Clinical SciencesFaculty of Health SciencesDepartment of Hand and Plastic SurgeryDepartment of Clinical and Experimental MedicineDivision of Community MedicinePain and Rehabilitation CenterDivision of Neuro and Inflammation ScienceDepartment of Dermatology and Venerology
Medical BiotechnologyCell and Molecular Biology

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