Sustained release of human platelet lysate growth factors by thermosensitive hydroxybutyl chitosan hydrogel promotes skin wound healing in rats

: Skin wound healing is a complex and dynamic process that involves angiogenesis and growth factor secretion. Newly formed vessels can provide nutrition and oxygen for skin wound healing. Growth factors in skin wounds are important for keratinocytes and fibroblasts proliferation, epithelialization, extracellular matrix remodeling, and angiogenesis, which accelerate skin wound healing. Therefore, treatment strategies that enhance angiogenesis and growth factors secretion in skin wounds can accelerate skin wound healing. This study investigated the effects of a SIKVAV (Ser-Ile-Lys-Val-Ala-Val) peptide-modified chitosan hydrogel on skin wound healing. Hematoxylin and eosin (H&E) staining demonstrated that the SIKVAV-modified chitosan hydrogel accelerated the re-epithelialization of wounds compared with that seen in the negative and positive controls. Masson’s trichrome staining showed that more collagen fibers were deposited in the skin wounds treated with the SIKVAV-modified chitosan hydrogel than in the negative and positive controls. Immunohistochemistry assays demonstrated that more myofibroblasts were deposited and more angiogenesis occurred in skin wounds treated with the SIKVAV-modified chitosan hydrogel than in the negative and positive controls. In addition, ELISA assays showed that the SIKVAV-modified chitosan hydrogels promoted the secretion of growth factors in skin wounds. Taken together, these results suggest that the SIKVAV-modified chitosan hydrogel has the potential to be developed as synthesized biomaterials for the treatment of skin wounds.

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The Effect of a Polyester Nanofibrous Membrane with a Fibrin-Platelet Lysate Coating on Keratinocytes and Endothelial Cells in a Co-Culture System

Nanomaterials ◽

10.3390/nano11020457 ◽

2021 ◽

Vol 11 (2) ◽

pp. 457

Author(s):

Andreu Blanquer ◽

Jana Musilkova ◽

Elena Filova ◽

Johanka Taborska ◽

Eduard Brynda ◽

...

Keyword(s):

Wound Healing ◽

Endothelial Cells ◽

Chronic Wounds ◽

Human Keratinocytes ◽

Skin Wound ◽

Platelet Lysate ◽

Therapeutic Approaches ◽

Skin Wound Healing ◽

New Therapeutic Approaches ◽

Proliferation And Differentiation

Chronic wounds affect millions of patients worldwide, and it is estimated that this number will increase steadily in the future due to population ageing. The research of new therapeutic approaches to wound healing includes the development of nanofibrous meshes and the use of platelet lysate (PL) to stimulate skin regeneration. This study considers a combination of a degradable electrospun nanofibrous blend of poly(L-lactide-co-ε-caprolactone) and poly(ε-caprolactone) (PLCL/PCL) membranes (NF) and fibrin loaded with various concentrations of PL aimed at the development of bioactive skin wound healing dressings. The cytocompatibility of the NF membranes, as well as the effect of PL, was evaluated in both monocultures and co-cultures of human keratinocytes and human endothelial cells. We determined that the keratinocytes were able to adhere on all the membranes, and their increased proliferation and differentiation was observed on the membranes that contained fibrin with at least 50% of PL (Fbg + PL) after 14 days. With respect to the co-culture experiments, the membranes with fibrin with 20% of PL were observed to enhance the metabolic activity of endothelial cells and their migration, and the proliferation and differentiation of keratinocytes. The results suggest that the newly developed NF combined with fibrin and PL, described in the study, provides a promising dressing for chronic wound healing purposes.

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Film Dressings Based on Hydrogels: Simultaneous and Sustained-Release of Bioactive Compounds with Wound Healing Properties

Pharmaceutics ◽

10.3390/pharmaceutics11090447 ◽

2019 ◽

Vol 11 (9) ◽

pp. 447 ◽

Cited By ~ 7

Author(s):

Fabian Ávila-Salas ◽

Adolfo Marican ◽

Soledad Pinochet ◽

Gustavo Carreño ◽

Oscar Valdés ◽

...

Keyword(s):

Wound Healing ◽

Sustained Release ◽

Bioactive Compounds ◽

Target Therapy ◽

Dicarboxylic Acids ◽

Skin Wound ◽

Dynamics Simulation ◽

Skin Wound Healing

This research proposes the rational modeling, synthesis and evaluation of film dressing hydrogels based on polyvinyl alcohol crosslinked with 20 different kinds of dicarboxylic acids. These formulations would allow the sustained release of simultaneous bioactive compounds including allantoin, resveratrol, dexpanthenol and caffeic acid as a multi-target therapy in wound healing. Interaction energy calculations and molecular dynamics simulation studies allowed evaluating the intermolecular affinity of the above bioactive compounds by hydrogels crosslinked with the different dicarboxylic acids. According to the computational results, the hydrogels crosslinked with succinic, aspartic, maleic and malic acids were selected as the best candidates to be synthesized and evaluated experimentally. These four crosslinked hydrogels were prepared and characterized by FTIR, mechanical properties, SEM and equilibrium swelling ratio. The sustained release of the bioactive compounds from the film dressing was investigated in vitro and in vivo. The in vitro results indicate a good release profile for all four analyzed bioactive compounds. More importantly, in vivo experiments suggest that prepared formulations could considerably accelerate the healing rate of artificial wounds in rats. The histological studies show that these formulations help to successfully reconstruct and thicken epidermis during 14 days of wound healing. Moreover, the four film dressings developed and exhibited excellent biocompatibility. In conclusion, the novel film dressings based on hydrogels rationally designed with combinatorial and sustained release therapy could have significant promise as dressing materials for skin wound healing.

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P-07 FREEZING/THAWING CYCLES OF DONOR PLATELET APHERESIS PRODUCE VARIABLE LEVELS OF GROWTH FACTORS IN HUMAN PLATELET LYSATE

Transfusion and Apheresis Science ◽

10.1016/s1473-0502(12)70043-5 ◽

2012 ◽

Vol 47 ◽

pp. S24-S25

Author(s):

M. Bernardi ◽

E. Albiero ◽

S. Castegnaro ◽

K. Chieregato ◽

C. Lievore ◽

...

Keyword(s):

Growth Factors ◽

Human Platelet ◽

Platelet Lysate ◽

Human Platelet Lysate

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Comparison of the efficacy of cryopreserved human platelet lysate and refrigerated lyophilized human platelet lysate for wound healing

Regenerative Therapy ◽

10.1016/j.reth.2018.10.003 ◽

2019 ◽

Vol 10 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Sharon Claudia Notodihardjo ◽

Naoki Morimoto ◽

Natsuko Kakudo ◽

Toshihito Mitsui ◽

Tien Minh Le ◽

...

Keyword(s):

Wound Healing ◽

Human Platelet ◽

Platelet Lysate ◽

Human Platelet Lysate

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Peptide-Modified Chitosan Hydrogels Accelerate Skin Wound Healing by Promoting Fibroblast Proliferation, Migration, and Secretion

Cell Transplantation ◽

10.1177/0963689717721216 ◽

2017 ◽

Vol 26 (8) ◽

pp. 1331-1340 ◽

Cited By ~ 18

Author(s):

Xionglin Chen ◽

Min Zhang ◽

Shixuan Chen ◽

Xueer Wang ◽

Zhihui Tian ◽

...

Keyword(s):

Wound Healing ◽

Growth Factors ◽

Skin Wound ◽

Skin Wounds ◽

Skin Wound Healing ◽

Promote Cell Proliferation ◽

Modified Chitosan ◽

Chitosan Hydrogels ◽

Positive Controls

Skin wound healing is a complicated process that involves a variety of cells and cytokines. Fibroblasts play an important role in this process and participate in transformation into myofibroblasts, the synthesis of extracellular matrix (ECM) and fibers, and the secretion of a variety of growth factors. This study assessed the effects of peptide Ser-Ile-Lys-Val-Ala-Val (SIKVAV)--modified chitosan hydrogels on skin wound healing. We investigated the capability of peptide SIKVAV to promote cell proliferation and migration, the synthesis of collagen, and the secretion of a variety of growth factors using fibroblasts in vitro. We also treated skin wounds established in mice using peptide SIKVAV-modified chitosan hydrogels. Hematoxylin and eosin staining showed that peptide-modified chitosan hydrogels enhanced the reepithelialization of wounds compared with negative and positive controls. Masson’s trichrome staining demonstrated that more collagen fibers were deposited in the wounds treated with peptide-modified chitosan hydrogels compared with the negative and positive controls. Immunohistochemistry revealed that the peptide-modified chitosan hydrogels promoted angiogenesis in the skin wound. Taken together, these results suggest that peptide SIKVAV-modified chitosan hydrogels may be useful in wound dressing and the treatment of skin wounds.

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A laminin mimetic peptide SIKVAV-conjugated chitosan hydrogel promoting wound healing by enhancing angiogenesis, re-epithelialization and collagen deposition

Journal of Materials Chemistry B ◽

10.1039/c5tb00842e ◽

2015 ◽

Vol 3 (33) ◽

pp. 6798-6804 ◽

Cited By ~ 28

Author(s):

Shixuan Chen ◽

Min Zhang ◽

Xuebing Shao ◽

Xueer Wang ◽

Lei Zhang ◽

...

Keyword(s):

Wound Healing ◽

Skin Wound ◽

Collagen Deposition ◽

Critical Factors ◽

Skin Wound Healing ◽

Chitosan Hydrogel ◽

Mimetic Peptide

Angiogenesis and re-epithelialization are critical factors in skin wound healing.

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Developing a Glyoxal-Crosslinked Chitosan/Gelatin Hydrogel for Sustained Release of Human Platelet Lysate to Promote Tissue Regeneration

International Journal of Molecular Sciences ◽

10.3390/ijms22126451 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6451

Author(s):

Ching-Cheng Tsai ◽

Tai-Horng Young ◽

Guang-Shih Chen ◽

Nai-Chen Cheng

Keyword(s):

Growth Factor ◽

Sustained Release ◽

Tissue Regeneration ◽

Transforming Growth Factor ◽

Human Platelet ◽

Umbilical Vein ◽

Platelet Lysate ◽

Release Pattern ◽

Human Platelet Lysate

The clinical application of human platelet lysate (HPL) holds promise for tissue regeneration, and the development of an efficient vehicle for its delivery is desired. Chitosan-based hydrogels are potential candidates, but they often exhibit weak mechanical properties. In this study, a chitosan/gelatin (CS-GE) hydrogel crosslinked by glyoxal was fabricated for sustained release of HPL. The influence of HPL on Hs68 fibroblast and human umbilical vein endothelial cell (HUVEC) culture was evaluated, and we found that supplementing 5% HPL in the medium could significantly improve cell proliferation relative to supplementing 10% fetal bovine serum (FBS). Moreover, HPL accelerated the in vitro wound closure of Hs68 cells and facilitated the tube formation of HUVECs. Subsequently, we fabricated CS-GE hydrogels crosslinked with different concentrations of glyoxal, and the release pattern of FITC-dextrans (4, 40 and 500 kDa) from the hydrogels was assessed. After an ideal glyoxal concentration was determined, we further characterized the crosslinked CS-GE hydrogels encapsulated with different amounts of HPL. The HPL-incorporated hydrogel was shown to significantly promote the proliferation of Hs68 cells and the migration of HUVECs. Moreover, the release pattern of transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor-BB (PDGF-BB) from hydrogel was examined in vitro, demonstrating a sustained release profile of the growth factors. Finally, the chick chorioallantoic membrane assay revealed that HPL encapsulation in the hydrogel significantly stimulated angiogenesis in ovo. These results demonstrate the great potential of the crosslinked CS-GE hydrogel to serve as an effective delivery system for HPL to promote tissue regeneration.

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Features of skin wound healing in rats with experimental chronic kidney disease

Regulatory Mechanisms in Biosystems ◽

10.15421/022181 ◽

2021 ◽

Vol 12 (4) ◽

pp. 594-598

Author(s):

S. B. Pavlov ◽

O. B. Litvinova ◽

N. M. Babenko

Keyword(s):

Chronic Kidney Disease ◽

Wound Healing ◽

Growth Factors ◽

Kidney Disease ◽

Wound Repair ◽

Histological Analysis ◽

Kidney Diseases ◽

Skin Wound ◽

Control Group ◽

Skin Wound Healing

Chronic kidney disease negatively affects the morphofunctional state of all organs due to hemodynamic and metabolic disorders. Changes in the content of cytokines observed in kidney diseases, which regulate the processes of inflammation and tissue repair, can complicate the course of the wound process. This research aimed to study disorders in the process of skin wound repair due to changes in the dynamics of production of interleukins IL-1β, IL-6, IL-10, IL-4, growth factors bFGF and VEGF in animals with experimental chronic kidney disease. The levels of interleukins and growth factors were determined on the 7th, 14th and 28th days after surgical modeling of wounds in the blood of rats with experimental chronic kidney disease and animals of the control group. To assess the dynamics and quality of wound healing, a semi-quantitative histological analysis was performed. The study showed an increase in the content of pro-inflammatory interleukins in the group of sick rats: on the 7th day the level of IL-1β was 1.19 times higher, and IL-6 – 1.55 times, on the 14th day the level of IL-1β was 1.37 times in comparison with the control group. The maximum increase in the concentration of anti-inflammatory interleukins was noted on the 28th day: IL-4 was 2.10 times higher, IL-10 – 1.39 times higher than in the control group. The content of bFGF and VEGF in animals of the control group reached its maximum on the 7th day, and in animals with chronic kidney disease – on the 15th day after surgery. Semi-quantitative histological analysis showed a decrease in indicators in the group of sick animals: the number of fibroblasts and collagen deposition – on the 7th day, reepithelialization – on the 28th day. A persistent increase in the number of polymorphonuclear leukocytes was also noted at all periods of the experiment: by 1.38, 1.99, and 9.82 times – on the 7th, 14th, and 28th days, respectively. The study showed that the dynamics of the production of interleukins and growth factors were impaired in rats with chronic kidney disease. In the process of damage regeneration in sick animals, pro-inflammatory mechanisms prevailed with the involvement of a large number of immunocompetent cells, as a result, skin wounds took longer to heal.

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