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Pharmaceuticals
Special Issues
Formulations for Wound Healing
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Formulations for Wound Healing

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (1 October 2021) | Viewed by 58124

Special Issue Editors

Dr. Takehisa Hanawa

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Guest Editor
Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
Interests: pre-formulation; solid dispersion; hydrogel; wound healing; semi-solid formulation; prevention of stomatitis; nanoparticle; grinding; DSC; PXRD
Special Issues, Collections and Topics in MDPI journals
Dr. Yayoi Kawano

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Guest Editor
Department of Pharmacy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Tokyo 162-8601, Japan
Interests: hydrogel; pharmaceutical applications; bio medical applications; drug delivery system; tissue engineering
Special Issues, Collections and Topics in MDPI journals
Dr. Viorica Patrulea

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Guest Editor
Department of Engineering Science, Institute of Biomedical Engineering, University of Oxford, Old Road Campus Research Building, Headington, Oxford OX3 7DQ, UK
Interests: wound healing; chronic wounds; hard-to-heal wounds; antimicrobial resistance; wound infection; antimicrobial agents; nanocomplexes; biopolymers
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Mitsutoshi Sato

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Guest Editor
Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, Meiji Pharmaceutical University, Tokyo 204-8588, Japan
Interests: toxcology; pharmacology; prevention and treatment of drug adverse events
Dr. Olivier Jordan

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Guest Editor
Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1, Rue Michel Servet, 1211 Geneva, Switzerland
Interests: drug delivery; pharmaceutical sciences; antimicrobial peptide
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In the United States, about 65 million people need wound treatment annually, so it can be said that the global need for wound treatment preparations is high. The market for wound dressings is expected to expand further in the future, as the number of patients with pressure ulcer increases due to the aging of society. Currently, "surgical treatment", "treatment with a dressing", "drug therapy", and the like are performed to treat wounds. Among them, "treatment with a dressing", consisting in covering wounds with a protection, is very common in the medical field. Therefore, wound dressings made of new materials that can be easily handled by anyone and are functional are highly desirable.

This Special Issue will focus on various aspects of wound treatment, such as (1) status quo of wound healing therapy, (2) pharmacological approaches to wound treatment, (3) biopharmaceutical approaches, (4) pharmaceutical approaches, (5) development of devices to improve wound healing. The overall perception of current wound treatment strategies will also be discussed.

Dr. Takehisa Hanawa
Prof. Dr. Mitsutoshi Sato
Dr. Olivier Jordan
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Wound healing
  • Status quo of wound healing therapy
  • Biopharmaceutical approach to wound healing
  • Pharmaceutical approach to wound healing
  • Development of devices for wound healing

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Published Papers (7 papers)

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Research

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16 pages, 2410 KiB  
Article
Anti-Aging β-Klotho Gene-Activated Scaffold Promotes Rejuvenative Wound Healing Response in Human Adipose-Derived Stem Cells
by Ashang L. Laiva, Fergal J. O’Brien and Michael B. Keogh
Pharmaceuticals 2021, 14(11), 1168; https://doi.org/10.3390/ph14111168 - 17 Nov 2021
Cited by 9 | Viewed by 3673
Abstract
Wound healing requires a tight orchestration of complex cellular events. Disruption in the cell-signaling events can severely impair healing. The application of biomaterial scaffolds has shown healing potential; however, the potential is insufficient for optimal wound maturation. This study explored the functional impact [...] Read more.
Wound healing requires a tight orchestration of complex cellular events. Disruption in the cell-signaling events can severely impair healing. The application of biomaterial scaffolds has shown healing potential; however, the potential is insufficient for optimal wound maturation. This study explored the functional impact of a collagen-chondroitin sulfate scaffold functionalized with nanoparticles carrying an anti-aging gene β-Klotho on human adipose-derived stem cells (ADSCs) for rejuvenative healing applications. We studied the response in the ADSCs in three phases: (1) transcriptional activities of pluripotency factors (Oct-4, Nanog and Sox-2), proliferation marker (Ki-67), wound healing regulators (TGF-β3 and TGF-β1); (2) paracrine bioactivity of the secretome generated by the ADSCs; and (3) regeneration of basement membrane (fibronectin, laminin, and collagen IV proteins) and expression of scar-associated proteins (α-SMA and elastin proteins) towards maturation. Overall, we found that the β-Klotho gene-activated scaffold offers controlled activation of ADSCs’ regenerative abilities. On day 3, the ADSCs on the gene-activated scaffold showed enhanced (2.5-fold) activation of transcription factor Oct-4 that was regulated transiently. This response was accompanied by a 3.6-fold increase in the expression of the anti-fibrotic gene TGF-β3. Through paracrine signaling, the ADSCs-laden gene-activated scaffold also controlled human endothelial angiogenesis and pro-fibrotic response in dermal fibroblasts. Towards maturation, the ADSCs-laden gene-activated scaffold further showed an enhanced regeneration of the basement membrane through increases in laminin (2.1-fold) and collagen IV (8.8-fold) deposition. The ADSCs also expressed 2-fold lower amounts of the scar-associated α-SMA protein with improved qualitative elastin matrix deposition. Collectively, we determined that the β-Klotho gene-activated scaffold possesses tremendous potential for wound healing and could advance stem cell-based therapy for rejuvenative healing applications. Full article
(This article belongs to the Special Issue Formulations for Wound Healing)
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24 pages, 163179 KiB  
Article
Evaluation of the Healing Effect of Ointments Based on Bee Products on Cutaneous Lesions in Wistar Rats
by Calin Vasile Andritoiu, Cristina Lungu, Maricel Danu, Bianca Ivanescu, Corina Elena Andriescu, Laurian Vlase, Corneliu Havarneanu, Camelia Elena Iurciuc (Tincu) and Marcel Popa
Pharmaceuticals 2021, 14(11), 1146; https://doi.org/10.3390/ph14111146 - 11 Nov 2021
Cited by 2 | Viewed by 3060
Abstract
The wound-healing capacity of ointments based on bee products was investigated in vivo on three experimental models of incision, excision and heat burn. For this purpose, four ointments were prepared with propolis, honey, apilarnil (drone brood homogenate) and a mixture of these three [...] Read more.
The wound-healing capacity of ointments based on bee products was investigated in vivo on three experimental models of incision, excision and heat burn. For this purpose, four ointments were prepared with propolis, honey, apilarnil (drone brood homogenate) and a mixture of these three apitherapy products. The ointments were applied topically for 21 days. Clinical and macroscopic evaluation was performed throughout the experiment, with the recording of the re-epithelialization period and determination of the wound contraction rate on days 6 and 9. The histopathological examination was performed on days 1, 3, 12 and 21 of the treatment. The topical formulations were also characterized from a rheological point of view in order to verify their stability. HPLC analysis of propolis revealed the presence of phenolic compounds, particularly ferulic acid and p-coumaric which were found in high amounts. All ointments had beneficial effects on wound contraction and the re-epithelialization period, but the most significant result, both macroscopically and especially in terms of histological architecture, was presented by the ointment that contains all three apitherapy products, due to their synergistic effect. Full article
(This article belongs to the Special Issue Formulations for Wound Healing)
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17 pages, 6251 KiB  
Article
Evaluation of the Wound Healing Potential of Some Natural Polymers on Three Experimental Models
by Calin Vasile Andritoiu, Corina Elena Andriescu, Maricel Danu, Cristina Lungu, Bianca Ivanescu, Cornel Havarneanu and Marcel Popa
Pharmaceuticals 2021, 14(5), 465; https://doi.org/10.3390/ph14050465 - 14 May 2021
Cited by 4 | Viewed by 3434
Abstract
The aim of this paper was the preparation and investigation of the wound healing properties of four topical formulations based on natural polymers such as collagen, chitosan, lyophilized egg white, and a mixture of them. The therapeutic assessment of these four ointments was [...] Read more.
The aim of this paper was the preparation and investigation of the wound healing properties of four topical formulations based on natural polymers such as collagen, chitosan, lyophilized egg white, and a mixture of them. The therapeutic assessment of these four ointments was carried out in vivo on the incision, excision, and thermal burn wounds induced on Wistar rats. The treatment was applied topically on wounds once a day, for 21 days. The experimental results were analyzed from a clinical and histopathological point of view. The rheological characterization of the topical formulations was also performed in order to verify their spreadability and structural stability. All ointments had a positive effect on wound contraction and re-epithelization processes, but the one based on total polymers had a significant healing potential on the designed cutaneous lesions due to its synergistic effects. Full article
(This article belongs to the Special Issue Formulations for Wound Healing)
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18 pages, 5286 KiB  
Article
Wound Healing Promotion by Hyaluronic Acid: Effect of Molecular Weight on Gene Expression and In Vivo Wound Closure
by Yayoi Kawano, Viorica Patrulea, Emmanuelle Sublet, Gerrit Borchard, Takuya Iyoda, Rihoko Kageyama, Asa Morita, Satoshi Seino, Hideto Yoshida, Olivier Jordan and Takehisa Hanawa
Pharmaceuticals 2021, 14(4), 301; https://doi.org/10.3390/ph14040301 - 28 Mar 2021
Cited by 70 | Viewed by 7672
Abstract
Hyaluronic acid (HA) has been known to play an important role in wound healing process. However, the effect of molecular weight (MW) of exogenously administered HA on the wound healing process has not been fully understood. In this study, we investigated HA with [...] Read more.
Hyaluronic acid (HA) has been known to play an important role in wound healing process. However, the effect of molecular weight (MW) of exogenously administered HA on the wound healing process has not been fully understood. In this study, we investigated HA with different MWs on wound healing process using human epidermal keratinocytes and dermal fibroblasts. Cell proliferation and migration ability were assessed by water soluble tetrazolium (WST) assay and wound scratch assay. We examined the effect of HA addition in a full-thickness wound model in mice and the gene expression related to wound healing. Proliferation and migration of HaCaT cells increased with the increase of MW and concentration of HA. Interleukin (IL-1β), IL-8 and vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase (MMP)-9 and MMP-13 were significantly upregulated by high molecular weight (HMW) HA in keratinocytes. Together with VEGF upregulation and the observed promotion of HaCaT migration, HA with the MW of 2290 kDa may hold potential to improve re-epithelialization, a critical obstacle to heal chronic wounds. Full article
(This article belongs to the Special Issue Formulations for Wound Healing)
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28 pages, 3263 KiB  
Article
Retrospective Evaluation of Progenitor Biological Bandage Use: A Complementary and Safe Therapeutic Management Option for Prevention of Hypertrophic Scarring in Pediatric Burn Care
by Karim Al-Dourobi, Alexis Laurent, Lina Deghayli, Marjorie Flahaut, Philippe Abdel-Sayed, Corinne Scaletta, Murielle Michetti, Laurent Waselle, Jeanne-Pascale Simon, Oumama El Ezzi, Wassim Raffoul, Lee Ann Applegate, Nathalie Hirt-Burri and Anthony S de Buys Roessingh
Pharmaceuticals 2021, 14(3), 201; https://doi.org/10.3390/ph14030201 - 28 Feb 2021
Cited by 14 | Viewed by 3499
Abstract
Progenitor Biological Bandages (PBB) have been continuously applied clinically in the Lausanne Burn Center for over two decades. Vast translational experience and hindsight have been gathered, specifically for cutaneous healing promotion of donor-site grafts and second-degree pediatric burns. PBBs constitute combined Advanced Therapy [...] Read more.
Progenitor Biological Bandages (PBB) have been continuously applied clinically in the Lausanne Burn Center for over two decades. Vast translational experience and hindsight have been gathered, specifically for cutaneous healing promotion of donor-site grafts and second-degree pediatric burns. PBBs constitute combined Advanced Therapy Medicinal Products, containing viable cultured allogeneic fetal dermal progenitor fibroblasts. Such constructs may partly favor repair and regeneration of functional cutaneous tissues by releasing cytokines and growth factors, potentially negating the need for subsequent skin grafting, while reducing the formation of hypertrophic scar tissues. This retrospective case-control study (2010–2018) of pediatric second-degree burn patients comprehensively compared two initial wound treatment options (i.e., PBBs versus Aquacel® Ag, applied during ten to twelve days post-trauma). Results confirmed clinical safety of PBBs with regard to morbidity, mortality, and overall complications. No difference was detected between groups for length of hospitalization or initial relative burn surface decreasing rates. Nevertheless, a trend was observed in younger patients treated with PBBs, requiring fewer corrective interventions or subsequent skin grafting. Importantly, significant improvements were observed in the PBB group regarding hypertrophic scarring (i.e., reduced number of scar complications and related corrective interventions). Such results establish evidence of clinical benefits yielded by the Swiss fetal progenitor cell transplantation program and favor further implementation of specific cell therapies in highly specialized regenerative medicine. Full article
(This article belongs to the Special Issue Formulations for Wound Healing)
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Review

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11 pages, 1413 KiB  
Review
Polydeoxyribonucleotide: A Promising Biological Platform to Accelerate Impaired Skin Wound Healing
by Mariarosaria Galeano, Giovanni Pallio, Natasha Irrera, Federica Mannino, Alessandra Bitto, Domenica Altavilla, Mario Vaccaro, Giovanni Squadrito, Vincenzo Arcoraci, Michele Rosario Colonna, Rita Lauro and Francesco Squadrito
Pharmaceuticals 2021, 14(11), 1103; https://doi.org/10.3390/ph14111103 - 29 Oct 2021
Cited by 21 | Viewed by 10317
Abstract
The normal wound healing process is characterized by a complex, highly integrated cascade of events, requiring the interactions of many cell types, including inflammatory cells, fibroblasts, keratinocytes and endothelial cells, as well as the involvement of growth factors and enzymes. However, several diseases [...] Read more.
The normal wound healing process is characterized by a complex, highly integrated cascade of events, requiring the interactions of many cell types, including inflammatory cells, fibroblasts, keratinocytes and endothelial cells, as well as the involvement of growth factors and enzymes. However, several diseases such as diabetes, thermal injury and ischemia could lead to an impaired wound healing process characterized by wound hypoxia, high levels of oxygen radicals, reduced angiogenesis, decreased collagen synthesis and organization. Polydeoxyribonucleotide (PDRN) has been used to improve wound healing through local and systemic administration thanks to its ability to promote cell migration and growth, angiogenesis, and to reduce inflammation on impaired wound healing models in vitro, in vivo and clinical studies. In light of all these observations, the aim of this review is to provide a full overview of PDRN applications on skin regeneration. We reviewed papers published in the last 25 years on PubMed, inserting “polydeoxyribonucleotide and wound healing” as the main search term. All data obtained proved the ability of PDRN in promoting physiological tissue repair through adenosine A2A receptor activation and salvage pathway suggesting that PDRN has proven encouraging results in terms of healing time, wound regeneration and absence of side effects. Full article
(This article belongs to the Special Issue Formulations for Wound Healing)
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17 pages, 1806 KiB  
Review
Periodontal Wound Healing and Tissue Regeneration: A Narrative Review
by Young-Dan Cho, Kyoung-Hwa Kim, Yong-Moo Lee, Young Ku and Yang-Jo Seol
Pharmaceuticals 2021, 14(5), 456; https://doi.org/10.3390/ph14050456 - 12 May 2021
Cited by 75 | Viewed by 23467
Abstract
Periodontal disease is a major public health issue, and various periodontal therapies have been performed to regenerate periodontal tissues. The periodontium is a complex structure composed of specialized tissues that support the teeth, and most periodontal surgeries are invasive procedures, including a resection [...] Read more.
Periodontal disease is a major public health issue, and various periodontal therapies have been performed to regenerate periodontal tissues. The periodontium is a complex structure composed of specialized tissues that support the teeth, and most periodontal surgeries are invasive procedures, including a resection of the gingiva or the alveolar bone. The periodontal wound healing process is slightly different from cutaneous wound healing and is similar to fetal healing, being almost scar-free. The aim of this review article is to provide an overview of periodontal wound healing and discuss various surgical and pharmaceutical approaches to achieve stable wound healing and improve the treatment outcomes. In addition, detrimental and limiting factors that induce a compromised prognosis are discussed, along with the perspective and future direction for successful periodontal tissue regeneration. Full article
(This article belongs to the Special Issue Formulations for Wound Healing)
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