Pullulan Hydrogels Improve Mesenchymal Stem Cell Delivery into High‐Oxidative‐Stress Wounds

Wong, Victor W.; Rustad, Kristine C.; Glotzbach, Jason P.; Sorkin, Michael; Inayathullah, Mohammed; Major, Melanie R.; Longaker, Michael T.; Rajadas, Jayakumar; Gurtner, Geoffrey C.

doi:10.1002/mabi.201100180

Cited by 95 publications

(64 citation statements)

References 46 publications

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“…Additionally, we delivered our macrophages using a biomimetic pullalan-collagen composite dermal hydrogel (18). Prior studies using this scaffold have demonstrated improved delivery of other cell types into wounds that have high oxidative stress (19). These technical modifications provide an improved understanding of the true effects of delivering macrophages/monocytes at supraphysiologic levels into wounds.…”

Section: Discussionmentioning

confidence: 99%

Delivery of monocyte lineage cells in a biomimetic scaffold enhances tissue repair

Walmsley

Barnes

et al. 2017

JCI Insight

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Section: Discussionmentioning

confidence: 99%

Delivery of monocyte lineage cells in a biomimetic scaffold enhances tissue repair

Walmsley

Barnes

et al. 2017

JCI Insight

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“…7 The compound is nontoxic, nonimmunogenic and nonmutagenic, and has good antioxidant potential. 7,8 These properties have shown that pullulan is an ideal compound for use in skin substitutes and can both be incorporated with and recruit viable skin cells. 8,9 On the other hand, gelatin is an irreversibly hydrolyzed form of collagen that has been used extensively in hydrogels.…”

Section: Introductionmentioning

confidence: 99%

Cellularized Bilayer Pullulan-Gelatin Hydrogel for Skin Regeneration

Nicholas

Jeschke

Amini-Nik

2016

Tissue Engineering Part A

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Skin substitutes significantly reduce the morbidity and mortality of patients with burn injuries and chronic wounds. However, current skin substitutes have disadvantages related to high costs and inadequate skin regeneration due to highly inflammatory wounds. Thus, new skin substitutes are needed. By combining two polymers, pullulan, an inexpensive polysaccharide with antioxidant properties, and gelatin, a derivative of collagen with high water absorbency, we created a novel inexpensive hydrogel-named PG-1 for ''pullulan-gelatin first generation hydrogel''-suitable for skin substitutes. After incorporating human fibroblasts and keratinocytes onto PG-1 using centrifugation over 5 days, we created a cellularized bilayer skin substitute. Cellularized PG-1 was compared to acellular PG-1 and no hydrogel (control) in vivo in a mouse excisional skin biopsy model using newly developed dome inserts to house the skin substitutes and prevent mouse skin contraction during wound healing. PG-1 had an average pore size of 61.69 mm with an ideal elastic modulus, swelling behavior, and biodegradability for use as a hydrogel for skin substitutes. Excellent skin cell viability, proliferation, differentiation, and morphology were visualized through live/dead assays, 5-bromo-2¢-deoxyuridine proliferation assays, and confocal microscopy. Trichrome and immunohistochemical staining of excisional wounds treated with the cellularized skin substitute revealed thicker newly formed skin with a higher proportion of actively proliferating cells and incorporation of human cells compared to acellular PG-1 or control. Excisional wounds treated with acellular or cellularized hydrogels showed significantly less macrophage infiltration and increased angiogenesis 14 days post skin biopsy compared to control. These results show that PG-1 has ideal mechanical characteristics and allows ideal cellular characteristics. In vivo evidence suggests that cellularized PG-1 promotes skin regeneration and may help promote wound healing in highly inflammatory wounds, such as burns and chronic wounds.

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“…Gurtner and co-workers developed a biomimetic hydrogel based on the carbohydrate pullulan that can quench free radicals and has potent antioxidative capabilities. [ 56,57 ] Mouse MSCs were seeded onto the hydrogel and more than 95% of cells were found to be alive after culturing for 2 weeks, suggesting a good biocompatibility of the hydrogel. When exposed to toxic levels of H 2 O 2 (100 × 10 −6 M and 1 × 10 −3 M ), MSCs seeded in the hydrogel demonstrated markedly improved survival rates compared to the MSCs without hydrogel, indicating that pullulan-based hydrogels were able to protect seeded MSCs from oxidative stress.…”

Section: Materials Protecting Cells From Ros Damagementioning

confidence: 99%

Reactive Oxygen Species (ROS) Responsive Polymers for Biomedical Applications

Xiao

et al. 2016

Macromolecular Bioscience

304

202

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Reactive oxygen species (ROS) play important roles in cell signaling pathways, while increased production of ROS may disrupt cellular homeostasis, giving rise to oxidative stress and a series of diseases. Utilizing these cell‐generated species as triggers for selective tuning polymer structures and properties represents a promising methodology for disease diagnosis and treatment. Recently, significant progress has been made in fabricating biomaterials including nanoparticles and macroscopic networks to interact with this dynamic physiological condition. These ROS‐responsive platforms have shown potential in a range of biomedical applications, such as cancer targeted drug delivery systems, cell therapy platforms for inflammation related disease, and so on.

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Pullulan Hydrogels Improve Mesenchymal Stem Cell Delivery into High‐Oxidative‐Stress Wounds

Cited by 95 publications

References 46 publications

Delivery of monocyte lineage cells in a biomimetic scaffold enhances tissue repair

Delivery of monocyte lineage cells in a biomimetic scaffold enhances tissue repair

Cellularized Bilayer Pullulan-Gelatin Hydrogel for Skin Regeneration

Reactive Oxygen Species (ROS) Responsive Polymers for Biomedical Applications

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