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Exploring Novel Treatments for Wounds
Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Wound healing is a complex and dynamic process involving the interplay of various cellular and molecular mechanisms aimed at restoring skin integrity and function. Burns, a common type of acute wound, represent a significant challenge due to their high morbidity. Effective burn wound management requires advanced therapeutic strategies that create a favorable environment for healing through wound care, the use of advanced wound dressings, and surgical interventions including skin transplantation. There has been growing interest in novel approaches, such as biomaterials and cell-based therapies, which offer promising solutions for improving wound healing outcomes. This thesis explores innovative treatments designed to enhance wound healing, focusing on creating an optimal wound environment through assisted debridement and the use of biomaterials for dressings, dermal substitutes, and scaffolds for autologous cells.

In paper I, the potential of porous gelatin microcarriers (PGM) as a scaffold for delivering autologous keratinocytes and fibroblasts to wounds was investigated. In vitro experiments demonstrated that PGM supports cell attachment and proliferation, with an optimal transplantation time identified within 24 to 96 hours. Using a porcine model, wounds treated with cell-seeded PGM exhibited improved re-epithelialization compared to single-cell suspensions and untreated controls. Histological analysis revealed that the PGM were degraded within four weeks and supported the formation of a mature neo-epidermis, demonstrating its potential as an efficient and time-saving alternative to traditional cultured epidermal autografts.

The study presented in paper II assessed the efficacy of amino acid-buffered hypochlorite (AABH) as a debridement agent in an infected porcine burn model. AABH, in combination with mechanical debridement, was compared to mechanical debridement alone and untreated controls. AABH significantly improved the removal of necrotic tissue, reduced bacterial load, and promoted wound healing. These findings suggest that AABH could serve as an effective and accessible tool for wound debridement, particularly in settings where specialized surgical expertise is limited.

In paper III, a randomized clinical trial compared a bacterial cellulose (BC) dressing to a porcine xenograft (PX) dressing for treating partial-thickness burns. Wounds treated with the BC dressing demonstrated healing times comparable to those of the PX dressing. Additionally, there were no significant differences in infection rates, pain, impact on everyday life, length of hospital stay, dressing costs, need for surgical interventions, or scar assessment when comparing the two dressings. In conclusion, BC demonstrated equivalent effectiveness to PX, making it an alternative for burn wound management. Furthermore, a significant advantage of BC is that it is not animal-derived, addressing ethical and cultural concerns.

The study presented in paper IV explored the use of recombinant spider silk modified with bioactive fibronectin motifs (FN-silk) as a dermal substitute. Using a porcine full-thickness wound model, FN-silk was compared to the collagen-based matrix MatriDerm®. FN-silk demonstrated excellent biocompatibility, and the material was gradually degraded in vivo. Wounds treated with FN-silk displayed significantly enhanced re-epithelialization and higher elasticity compared to those treated with MatriDerm® or untreated controls. These results highlight FN-silk's potential as a next-generation biomaterial for promoting epidermal healing and dermal regeneration.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2025. , p. 87
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1966
National Category
Surgery
Identifiers
URN: urn:nbn:se:liu:diva-212623DOI: 10.3384/9789180759861ISBN: 9789180759854 (print)ISBN: 9789180759861 (electronic)OAI: oai:DiVA.org:liu-212623DiVA, id: diva2:1947439
Public defence
2025-05-08, Belladonna, Växthuset, Campus US, Linköping, 09:00
Opponent
Supervisors
Available from: 2025-03-26 Created: 2025-03-26 Last updated: 2025-03-26Bibliographically approved
List of papers
1. Transplantation of autologous cells and porous gelatin microcarriers to promote wound healing
Open this publication in new window or tab >>Transplantation of autologous cells and porous gelatin microcarriers to promote wound healing
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2021 (English)In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 47, no 3, p. 601-610Article in journal (Refereed) Published
Abstract [en]

Definitive treatment to achieve wound healing in major burns frequently include skin transplantation, where split-thickness skin grafts is considered gold standard. This method is associated with several drawbacks. To overcome these hurdles, efforts have been made to develop tissue engineered skin substitutes, often comprised of a combination of cells and biomaterials. In the present study, we aimed to investigate transplantation of autologous keratinocytes and fibroblasts seeded on porous gelatin microcarriers using a porcine wound model. Pre-seeded microcarriers were transplanted to a total of 168 surgical full-thickness wounds (2 cm diameter) on eight adult female pigs and covered with occlusive dressings. The experimental groups included wounds transplanted with microcarriers seeded with the combination of keratinocytes and fibroblasts, microcarriers seeded with each cell type individually, microcarriers without cells, each cell type in suspension, and NaCl control. Wounds were allowed to heal for one, two, four or eight weeks before being excised and fixated for subsequent histological and immunohistochemical analysis. In vitro, we confirmed that viable cells populate the surface and the pores of the microcarriers. In vivo, the microcarriers were to a large extent degraded after two weeks. After one week, all treatment groups, with the exception of microcarriers alone, displayed significantly thicker neo-epidermis compared to controls. After two weeks, wounds transplanted with microcarriers seeded with cells displayed significantly thicker neo-epidermis compared to controls. After four weeks there was no difference in the thickness of neo-epidermis. In conclusion, the experiments performed illustrate that autologous cells seeded on porous gelatin microcarriers stimulates the re-epithelialization of wounds. This method could be a promising candidate for skin transplantation. Future studies will focus on additional outcome parameters to evaluate long-term quality of healing following transplantation. (c) 2020 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Place, publisher, year, edition, pages
Elsevier Science Ltd, 2021
Keywords
Burns; Wound healing; Transplantation; Tissue engineering; Guided tissue regeneration
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-176186 (URN)10.1016/j.burns.2020.08.003 (DOI)000649382400012 ()32843238 (PubMedID)
Note

Funding Agencies|Swedish government [LIO-834921]; county councils, the ALF-agreement [LIO-834921]

Available from: 2021-06-09 Created: 2021-06-09 Last updated: 2025-03-26
2. Amino acid buffered hypochlorite facilitates debridement of porcine infected burn wounds
Open this publication in new window or tab >>Amino acid buffered hypochlorite facilitates debridement of porcine infected burn wounds
2023 (English)In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 49, no 6, p. 1363-1371Article in journal (Refereed) Published
Abstract [en]

Introduction: Removal of necrotic tissue is a vital step in the treatment of full-thickness burn wounds, with surgical debridement being the most effective method. Since minor burn wounds are typically treated on an outpatient basis where surgical capabilities can be limited there is a need for alternative treatment options. In this study we aim to evaluate the use of amino acid buffered hypochlorite (AABH) as a chemical enhancement for wound debridement in a porcine infected burn wound model.Method: A total of 60 full-thickness burn wounds, 3 cm in diameter, were created on four pigs using a standardized burn device. The wounds were inoculated with 107 colonyforming units (CFU) of S. aureus. The experimental groups included wounds debrided with a plastic curette, wounds debrided after pretreatment with AABH, and control wounds wiped with gauze. Wounds were treated twice per week for three weeks. Debridement, healing, and infection parameters were evaluated over time.Results: After one week, but not after two and three weeks, the curette and AABH groups had higher debrided weights compared to control (p < 0.05). Percentage of wound area adequately cleared from necrotic tissue was higher in the AABH-group compared to the curette-group and control, after one week. The earliest healing was measured in the AABH group after two weeks (5 % of wounds), which also had the most healed wounds after three weeks (55 %). In both the AABH and the curette groups, bacterial load had fallen below 10(5) CFU/g after two weeks. No CFU were detectable in the AABH group after three weeks. The AABH-group was also the easiest to debride.Conclusion: Our results indicate that AABH facilitates wound debridement and could be a helpful addition to an effective treatment modality for removal of necrotic tissue in full thickness burns.(c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
Debridement; Burns; Hypochlorite; Porcine model
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-198390 (URN)10.1016/j.burns.2022.11.011 (DOI)001074068400001 ()36543728 (PubMedID)
Note

Funding Agencies|RLS Global AB, Sweden

Available from: 2023-10-10 Created: 2023-10-10 Last updated: 2025-03-26
3. Biosynthetic cellulose compared to porcine xenograft in the treatment of partial-thickness burns: A randomised clinical trial
Open this publication in new window or tab >>Biosynthetic cellulose compared to porcine xenograft in the treatment of partial-thickness burns: A randomised clinical trial
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2022 (English)In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 48, no 5, p. 1236-1245Article in journal (Refereed) Published
Abstract [en]

Aim: The aim was to compare two dressing treatments for partial-thickness burns: biosynthetic cellulose dressing (BsC) (Epiprotect (R) S2Medical AB, Linkoping, Sweden) and porcine xenograft (EZ Derm (R), Molnlycke Health Care, Gothenburg, Sweden). Methods: Twenty-four adults with partial-thickness burns were included in this randomized clinical trial conducted at The Burn Centers in Linkoping and Uppsala, Sweden between June 2016 and November 2018. Time to healing was the primary outcome. Secondary outcomes were wound infection, pain, impact on everyday life, length of hospital stay, cost, and burn scar outcome (evaluated with POSAS). Results: We found no significant differences between the two dressing groups regarding time to healing, wound infection, pain, impact on everyday life, duration of hospital stay, cost, or burn scar outcome at the first follow up. Burn scar outcome at the 12-month follow up showed that the porcine xenograft group patients scored their scars higher on the POSAS items thickness (p = 0.048) and relief (p = 0.050). This difference was, however, not confirmed by the observer. Conclusions: The results showed the dressings performed similarly when used in adults with burns evaluated as partial thickness. (C) 2021 The Authors. Published by Elsevier Ltd.

Place, publisher, year, edition, pages
Elsevier Science Ltd, 2022
Keywords
Burn wound dressing; Cellulose dressing; Healing time; Partial thickness burn; Porcine skin
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-188627 (URN)10.1016/j.burns.2021.09.017 (DOI)000849634500024 ()34629186 (PubMedID)
Available from: 2022-09-20 Created: 2022-09-20 Last updated: 2025-03-26

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