Physically Crosslinked Chitosan/PVA Hydrogels Containing Honey and Allantoin with Long-Term Biocompatibility for Skin Wound Repair: An In Vitro and In Vivo Study

Chitosan/PVA hydrogel films crosslinked by the freeze–thaw method and containing honey and allantoin were prepared for application as wound dressing materials. The effects of the freeze–thaw process and the addition of honey and allantoin on the swelling, the gel content and the mechanical properties of the samples were evaluated. The physicochemical properties of the samples, with and without the freeze–thaw process, were compared using FTIR, DSC and XRD. The results showed that the freeze–thaw process can increase the crystallinity and thermal stability of chitosan/PVA films. The freeze–thaw process increased the gel content but did not have a significant effect on the tensile strength. The presence of honey reduced the swelling and the tensile strength of the hydrogels due to hydrogen bonding interactions with PVA and chitosan chains. Long-term cell culture experiments using normal human dermal fibroblast (NHDF) cells showed that the hydrogels maintained their biocompatibility, and the cells showed extended morphology on the surface of the hydrogels for more than 30 days. The presence of honey significantly increased the biocompatibility of the hydrogels. The release of allantoin from the hydrogel was studied and, according to the Korsmeyer–Peppas and Weibull models, the mechanism was mainly diffusional. The results for the antimicrobial activity against E. coli and S. aureus bacteria showed that the allantoin-containing samples had a more remarkable antibacterial activity against S. aureus. According to the wound healing experiments, 98% of the wound area treated by the chitosan/PVA/honey hydrogel was closed, compared to 89% for the control. The results of this study suggest that the freeze–thaw process is a non-toxic crosslinking method for the preparation of chitosan/PVA hydrogels with long term biocompatibility that can be applied for wound healing and skin tissue engineering.

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Systemic and topical administration of spermidine accelerates skin wound healing

10.21203/rs.3.rs-111107/v1 ◽

2020 ◽

Author(s):

Daisuke Ito ◽

Hiroyasu Ito ◽

Takayasu Ideta ◽

Ayumu Kanbe ◽

Soranobu Ninomiya ◽

...

Keyword(s):

Cell Proliferation ◽

Wound Healing ◽

Wound Repair ◽

Healing Process ◽

Topical Administration ◽

Skin Wound ◽

Wound Healing Process ◽

Skin Wound Healing

Abstract Background The skin wound healing process is regulated by various cytokines, chemokines, and growth factors. Recent reports have demonstrated that spermine/spermidine (SPD) promote wound healing through urokinase-type plasminogen activator (uPA)/uPA receptor (uPAR) signaling in vitro. Here, we investigated whether the systemic and topical administration of SPD would accelerate the skin wound-repair process in vivo.Methods A skin wound repair model was established using C57BL/6 J mice. SPD was mixed with white petrolatum for topical administration. For systemic administration, SPD mixed with drinking water was orally administered. Changes in wound size over time were calculated using digital photography.Results Systemic and topical SPD treatment significantly accelerated skin wound healing. The administration of SPD promoted the uPA/uPAR pathway in wound sites. Moreover, topical treatment with SPD enhanced the expression of IL-6 and TNF-α in wound sites. Scratch and cell proliferation assays revealed that SPD administration accelerated scratch wound closure and cell proliferation in vitro.Conclusion These results indicate that treatment with SPD promotes skin wound healing through activation of the uPA/uPAR pathway and induction of the inflammatory response in wound sites. The administration of SPD might contribute to new effective treatments to accelerate skin wound healing.

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Platelet-rich plasma accelerates skin wound healing by promoting re-epithelialization

Burns & Trauma ◽

10.1093/burnst/tkaa028 ◽

2020 ◽

Vol 8 ◽

Cited By ~ 1

Author(s):

Pengcheng Xu ◽

Yaguang Wu ◽

Lina Zhou ◽

Zengjun Yang ◽

Xiaorong Zhang ◽

...

Keyword(s):

Wound Healing ◽

Growth Factor ◽

Wound Repair ◽

Chronic Wounds ◽

Platelet Rich Plasma ◽

Skin Wound ◽

Local Inflammation ◽

Skin Wound Healing

Abstract Background Autologous platelet-rich plasma (PRP) has been suggested to be effective for wound healing. However, evidence for its use in patients with acute and chronic wounds remains insufficient. The aims of this study were to comprehensively examine the effectiveness, synergy and possible mechanism of PRP-mediated improvement of acute skin wound repair. Methods Full-thickness wounds were made on the back of C57/BL6 mice. PRP or saline solution as a control was administered to the wound area. Wound healing rate, local inflammation, angiogenesis, re-epithelialization and collagen deposition were measured at days 3, 5, 7 and 14 after skin injury. The biological character of epidermal stem cells (ESCs), which reflect the potential for re-epithelialization, was further evaluated in vitro and in vivo. Results PRP strongly improved skin wound healing, which was associated with regulation of local inflammation, enhancement of angiogenesis and re-epithelialization. PRP treatment significantly reduced the production of inflammatory cytokines interleukin-17A and interleukin-1β. An increase in the local vessel intensity and enhancement of re-epithelialization were also observed in animals with PRP administration and were associated with enhanced secretion of growth factors such as vascular endothelial growth factor and insulin-like growth factor-1. Moreover, PRP treatment ameliorated the survival and activated the migration and proliferation of primary cultured ESCs, and these effects were accompanied by the differentiation of ESCs into adult cells following the changes of CD49f and keratin 10 and keratin 14. Conclusion PRP improved skin wound healing by modulating inflammation and increasing angiogenesis and re-epithelialization. However, the underlying regulatory mechanism needs to be investigated in the future. Our data provide a preliminary theoretical foundation for the clinical administration of PRP in wound healing and skin regeneration.

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222. A new role for activin in endometrial restoration after menses

Reproduction Fertility and Development ◽

10.1071/srb08abs222 ◽

2008 ◽

Vol 20 (9) ◽

pp. 22

Author(s):

T. J. Kaitu'u-Lino ◽

D. J. Phillips ◽

N. B. Morison ◽

L. A. Salamonsen

Keyword(s):

Wound Healing ◽

Wound Repair ◽

Abnormal Uterine Bleeding ◽

Positive Control ◽

Activin A ◽

In Vivo Studies ◽

Skin Wound Healing ◽

Complete Repair

10% of Australian women suffer from abnormal uterine bleeding (AUB). To stop endometrial bleeding after menstruation, the endometrium must repair adequately. We propose that endometrial restoration after menstruation has characteristics of wound healing and that inadequate endometrial repair may result in AUB. In vivo studies support a contribution of activins to skin wound healing: in mice overexpressing activins' natural inhibitor, follistatin, wound healing is significantly delayed (1). We hypothesised that activin would enhance endometrial repair and examined its contribution using an in vitro wound healing model and our well characterised in vivo mouse model of endometrial breakdown and repair (2). For the in vitro model, confluent human endometrial epithelial cells (ECC-1 cell line) were wounded and treated with carrier protein (control, 0.1% BSA), activin A (50ng/mL) or EGF (positive control: 50ng/mL). Wound areas were quantitated daily for 6 days. For the in vivo study, serum follistatin levels were measured by ELISA in follistatin overexpressing mice (FS) (2) and wild-type (WT) littermates. Mice were induced to undergo endometrial breakdown and repair (mimicking menstruation in women). Activin βA was immunolocalised during endometrial repair, and extent of repair assessed using our morphological scoring system (2). ECC-1 wound repair was significantly (P < 0.05) enhanced by activin A treatment v. control from days 2–6 of culture. In WT mice, activin βA localised to areas of endometrial repair. Serum follistatin was significantly elevated in FS mice v. controls (33.3 ± 3.8 v 7.07 ± 1.8 ng/mL, P < 0.01). In FS mice (n = 8) only 50% of uterine sections showed complete repair after endometrial breakdown, significantly less than those from WT animals (n = 15, P < 0.05) where 85% of sections demonstrated complete repair. These results demonstrate for the first time that activin A functions to promote endometrial restoration following menses and that this can be delayed under physiological conditions: such studies indicate potential treatments for AUB. (1) Wankell et al. (2001) EMBO J 20:5361–5372 (2) Kaitu'u-Lino et al. (2007) Endocrinology 148:5105–5111

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Human interleukin-4–treated regulatory macrophages promote epithelial wound healing and reduce colitis in a mouse model

Science Advances ◽

10.1126/sciadv.aba4376 ◽

2020 ◽

Vol 6 (23) ◽

pp. eaba4376 ◽

Cited By ~ 1

Author(s):

Timothy S. Jayme ◽

Gabriella Leung ◽

Arthur Wang ◽

Matthew L. Workentine ◽

Sruthi Rajeev ◽

...

Keyword(s):

Wound Healing ◽

Healthy Volunteers ◽

Wound Repair ◽

Interleukin 4 ◽

Cellular Immunotherapy ◽

Blood Monocytes ◽

Systemic Delivery ◽

Epithelial Wound Healing

Murine alternatively activated macrophages can exert anti-inflammatory effects. We sought to determine if IL-4–treated human macrophages [i.e., hM(IL4)] would promote epithelial wound repair and can serve as a cell transfer treatment for inflammatory bowel disease (IBD). Blood monocytes from healthy volunteers and patients with active and inactive IBD were converted to hM(IL4)s. IL-4 treatment of blood-derived macrophages from healthy volunteers and patients with inactive IBD resulted in a characteristic CD206+CCL18+CD14low/− phenotype (RNA-seq revealed IL-4 affected expression of 996 genes). Conditioned media from freshly generated or cryopreserved hM(IL4)s promoted epithelial wound healing in part by TGF, and reduced cytokine-driven loss of epithelial barrier function in vitro. Systemic delivery of hM(IL4) to dinitrobenzene sulphonic acid (DNBS)–treated Rag1−/− mice significantly reduced disease. These findings from in vitro and in vivo analyses provide proof-of-concept support for the development of autologous M(IL4) transfer as a cellular immunotherapy for IBD.

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Injectable Nanocurcumin-Formulated Chitosan-g-Pluronic Hydrogel Exhibiting a Great Potential for Burn Treatment

Journal of Healthcare Engineering ◽

10.1155/2018/5754890 ◽

2018 ◽

Vol 2018 ◽

pp. 1-14 ◽

Cited By ~ 18

Author(s):

Le Hang Dang ◽

Thi Hiep Nguyen ◽

Ha Le Bao Tran ◽

Vu Nguyen Doan ◽

Ngoc Quyen Tran

Keyword(s):

Wound Healing ◽

Wound Repair ◽

Healing Process ◽

Nanocomposite Hydrogel ◽

Burn Wound ◽

Burn Treatment ◽

Nanocomposite Hydrogels ◽

Burn Wound Healing

Burn wound healing is a complex multifactorial process that relies on coordinated signaling molecules to succeed. Curcumin is believed to be a potent antioxidant and anti-inflammatory agent; therefore, it can prevent the prolonged presence of oxygen free radicals which is a significant factor causing inhabitation of optimum healing process. This study describes an extension of study about the biofunctional nanocomposite hydrogel platform that was prepared by using curcumin and an amphiphilic chitosan-g-pluronic copolymer specialized in burn wound healing application. This formular (nCur-CP, nanocomposite hydrogel) was a free-flowing sol at ambient temperature and instantly converted into a nonflowing gel at body temperature. In addition, the storage study determined the great stability level of nCur-CP in long time using UV-Vis and DLS. Morphology and distribution of nCur in its nanocomposite hydrogels were observed by SEM and TEM, respectively. In vitro studies suggested that nCur-CP exhibited well fibroblast proliferation and ability in antimicrobacteria. Furthermore, second- and third-degree burn wound models were employed to evaluate the in vivo wound healing activity of the nCur-CP. In the second-degree wound model, the nanocomposite hydrogel group showed a higher regenerated collagen density and thicker epidermis layer formation. In third degree, the nCur-CP group also exhibited enhancement of wound closure. Besides, in both models, the nanocomposite material-treated groups showed higher collagen content, better granulation, and higher wound maturity. Histopathologic examination also implied that the nanocomposite hydrogel based on nanocurcumin and chitosan could enhance burn wound repair. In conclusion, the biocompatible and injectable nanocomposite scaffold might have great potential to apply for wound healing.

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Platelet-Rich Plasma-Derived Exosomal USP15 Promotes Cutaneous Wound Healing via Deubiquitinating EIF4A1

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/9674809 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Yan Xu ◽

Ze Lin ◽

Lei He ◽

Yanzhen Qu ◽

Liu Ouyang ◽

...

Keyword(s):

Wound Healing ◽

Wound Repair ◽

Platelet Rich Plasma ◽

Healing Process ◽

Cell Counting ◽

Wound Healing Process ◽

Hacat Cells ◽

Epithelial Regeneration

Epithelial regeneration is an essential wound healing process, and recent work suggests that different types of exosomes (Exos) can improve wound repair outcomes by promoting such epithelial regeneration. Platelet-rich plasma (PRP) is known to facilitate enhanced wound healing, yet the mechanisms underlying its activity are poorly understood. To explore these mechanisms, we first isolated PRP-derived Exos (PRP-Exos). Using immortalized keratinocytes (HaCaT cells) treated with PBS, PRP, or PRP-Exos, we conducted a series of in vitro Cell Counting Kit-8 (CCK-8), EdU, scratch wound, and transwell assays. We then established a wound defect model in vivo in mice and assessed differences in the mRNA expression within these wounds to better understand the basis for PRP-mediated wound healing. The functions of PRP-Exos and USP15 in the context of wound healing were then confirmed through additional in vitro and in vivo experiments. We found that PRP-Exos effectively promoted the in vitro proliferation, migration, and wound healing activity of HaCaT cells. USP15 was further identified as a key mediator through which these PRP-Exos were able to promote tissue repair both in vitro and in vivo. At a mechanistic level, USP15 enhanced the functional properties of HaCaT cells by promoting EIF4A1 deubiquitination. Thus, PRP-Exos and USP15 represent promising tools that can promote wound healing via enhancing epithelial regeneration.

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Wound Healing Activities and Potential of Selected African Medicinal Plants and Their Synthesized Biogenic Nanoparticles

Plants ◽

10.3390/plants10122635 ◽

2021 ◽

Vol 10 (12) ◽

pp. 2635

Author(s):

Caroline Tyavambiza ◽

Phumuzile Dube ◽

Mediline Goboza ◽

Samantha Meyer ◽

Abram Madimabe Madiehe ◽

...

Keyword(s):

Wound Healing ◽

Medicinal Plants ◽

Wound Repair ◽

Chronic Wounds ◽

In Vivo Models ◽

Repair Mechanisms ◽

Treatment Of Wounds ◽

Biogenic Nanoparticles

In Africa, medicinal plants have been traditionally used as a source of medicine for centuries. To date, African medicinal plants continue to play a significant role in the treatment of wounds. Chronic wounds are associated with severe healthcare and socio-economic burdens despite the use of conventional therapies. Emergence of novel wound healing strategies using medicinal plants in conjunction with nanotechnology has the potential to develop efficacious wound healing therapeutics with enhanced wound repair mechanisms. This review identified African medicinal plants and biogenic nanoparticles used to promote wound healing through various mechanisms including improved wound contraction and epithelialization as well as antibacterial, antioxidant and anti-inflammatory activities. To achieve this, electronic databases such as PubMed, Scifinder® and Google Scholar were used to search for medicinal plants used by the African populace that were scientifically evaluated for their wound healing activities in both in vitro and in vivo models from 2004 to 2021. Additionally, data on the wound healing mechanisms of biogenic nanoparticles synthesized using African medicinal plants is included herein. The continued scientific evaluation of wound healing African medicinal plants and the development of novel nanomaterials using these plants is imperative in a bid to alleviate the detrimental effects of chronic wounds.

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Exosomes Derived from Human Bone Marrow Mesenchymal Stem Cells Stimulated by Deferoxamine Accelerate Cutaneous Wound Healing by Promoting Angiogenesis

BioMed Research International ◽

10.1155/2019/9742765 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 11

Author(s):

Jianing Ding ◽

Xin Wang ◽

Bi Chen ◽

Jieyuan Zhang ◽

Jianguang Xu

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Wound Repair ◽

Umbilical Vein ◽

Tube Formation ◽

Diabetic Rats

The exosomes are derived from mesenchymal stem cells (MSCs) and may be potentially used as an alternative for cell therapy, for treating diabetic wounds, and aid in angiogenesis. This study, aimed to investigate whether exosomes originated from bone marrow-derived MSCs (BMSCs) preconditioned by deferoxamine (DFO-Exos) exhibited superior proangiogenic property in wound repair and to explore the underlying mechanisms involved. Human umbilical vein endothelial cells (HUVECs) were used for assays involving cell proliferation, scratch wound healing, and tube formation. To test the effects in vivo, streptozotocin-induced diabetic rats were established. Two weeks after the procedure, histological analysis was used to measure wound-healing effects, and the neovascularization was evaluated as well. Our findings demonstrated that DFO-Exos activate the PI3K/AKT signaling pathway via miR-126 mediated PTEN downregulation to stimulate angiogenesis in vitro. This contributed to enhanced wound healing and angiogenesis in streptozotocin-induced diabetic rats in vivo. Our results suggest that, in cell-free therapies, exosomes derived from DFO preconditioned stem cells manifest increased proangiogenic ability.

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Mitogenic whey extract stimulates wound repair activity in vitro and promotes healing of rat incisional wounds

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2000.278.6.r1651 ◽

2000 ◽

Vol 278 (6) ◽

pp. R1651-R1660 ◽

Cited By ~ 24

Author(s):

Timothy E. Rayner ◽

Allison J. Cowin ◽

J. Gray Robertson ◽

Rodney D. Cooter ◽

Richard C. Harries ◽

...

Keyword(s):

Wound Healing ◽

Growth Factors ◽

Wound Repair ◽

Direct Action ◽

Bovine Milk ◽

In Vitro Models ◽

Individual Growth ◽

Dose Dependent Fashion

The ability of single growth factors to promote healing of normal and compromised wounds has been well described, but wound healing is a process requiring the coordinated action of multiple growth factors. Only the synergistic effect on wound healing of combinations containing at most two individual growth factors has been reported. We sought to assess the ability of a novel milk-derived growth factor-enriched preparation [mitogenic bovine whey extract (MBWE)], which contains six known growth factors, to promote repair processes in organotypic in vitro models and incisional wounds in vivo. MBWE stimulated the contraction of fibroblast-populated collagen lattices in a dose-dependent fashion and promoted the closure of excisional wounds in embryonic day 17 fetal rat skin. Application of MBWE increased incisional wound strength in normal animals on days 3, 5, 7, and 10 and reversed the decrease in wound strength observed following steroid treatment. Wound histology showed increased fibroblast numbers in wounds from normal and steroid-compromised animals. These data suggest the mixture of factors present in bovine milk exerts a direct action on the cells of cutaneous wound repair to enhance both normal and compromised healing.

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Simulation of lung alveolar epithelial wound healing in vitro

Journal of The Royal Society Interface ◽

10.1098/rsif.2010.0041 ◽

2010 ◽

Vol 7 (49) ◽

pp. 1157-1170 ◽

Cited By ~ 8

Author(s):

Sean H. J. Kim ◽

Michael A. Matthay ◽

Keith Mostov ◽

C. Anthony Hunt

Keyword(s):

Wound Healing ◽

In Silico ◽

Wound Repair ◽

Three Dimensional ◽

Alveolar Type ◽

Alveolar Epithelial ◽

Epithelial Wound Healing ◽

Additional Cell

The mechanisms that enable and regulate alveolar type II (AT II) epithelial cell wound healing in vitro and in vivo remain largely unknown and need further elucidation. We used an in silico AT II cell-mimetic analogue to explore and better understand plausible wound healing mechanisms for two conditions: cyst repair in three-dimensional cultures and monolayer wound healing. Starting with the analogue that validated for key features of AT II cystogenesis in vitro , we devised an additional cell rearrangement action enabling cyst repair. Monolayer repair was enabled by providing ‘cells’ a control mechanism to switch automatically to a repair mode in the presence of a distress signal. In cyst wound simulations, the revised analogue closed wounds by adhering to essentially the same axioms available for alveolar-like cystogenesis. In silico cell proliferation was not needed. The analogue recovered within a few simulation cycles but required a longer recovery time for larger or multiple wounds. In simulated monolayer wound repair, diffusive factor-mediated ‘cell’ migration led to repair patterns comparable to those of in vitro cultures exposed to different growth factors. Simulations predicted directional cell locomotion to be critical for successful in vitro wound repair. We anticipate that with further use and refinement, the methods used will develop as a rigorous, extensible means of unravelling mechanisms of lung alveolar repair and regeneration.

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