Fluorinated methacrylamide chitosan hydrogels enhance collagen synthesis in wound healing through increased oxygen availability

Patil, Pritam S.; Fountas-Davis, Natalie; Huang, He; Evancho-Chapman, M. Michelle; Fulton, Judith A.; Shriver, Leah P.; Leipzig, Nic D.

doi:10.1016/j.actbio.2016.03.022

Cited by 83 publications

(99 citation statements)

References 59 publications

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“…1) and characterized as previously described. 25, 38 Briefly, to prepare MACF first 3 wt% chitosan (ChitoClear 43010, Primex, Siglufjordur, Iceland) was dissolved in 2 vol% acetic acid:water. Fluorinated groups were added to chitosan by adding 0.14 M pentadecafluorooctanoyl chloride (Sigma-Aldrich, Saint Louis, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

“…38 Finally, small samples of each were dissolved in 2 vol% deuterated acetic acid/D 2 O and 1 H and 19 F nuclear magnetic resonance (NMR; Varian 500 MHz, Varian, Inc., Palo Alto, CA, USA) were conducted to find percent methacrylation and percent fluorination respectively as previously described. 25, 38 …”

Section: Methodsmentioning

confidence: 99%

“…Next, they were saturated with oxygen by bubbling the solution with pure gaseous O 2 to MACF gels for 30 min at 5 PSI as previously described. 25 …”

Section: Methodsmentioning

confidence: 99%

“…Chitosan is abundant in nature, biocompatible, non-toxic and is already used in many biomedical applications including wound healing. 12, 17, 25, 26, 38 Chitosan is useful in bioconjugation reactions as it contains free amines. Further, chitosan degrades via native hydrolases, such a as lysozyme, and the degradation kinetics can be tuned via deacetylation percentage.…”

Section: Introductionmentioning

confidence: 99%

“…38 More recently, in vivo studies conducted in a rat excisional wound healing model showed that oxygenating hydrogel sheets of MACF improved re-epithelization, collagen metabolism and deposition. 25 …”

Section: Introductionmentioning

confidence: 99%

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Fluorinated Methacrylamide Chitosan Hydrogels Enhance Cellular Wound Healing Processes

2017

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Low availability of oxygen can lead to stalled wound healing processes and chronic wounds. To address local hypoxia and to better understand direct cellular benefits, a perfluorocarbon (PFC) conjugated chitosan (MACF) hydrogel that delivers oxygen was created and applied for the first time to in vitro cultures of human dermal fibroblasts and human epidermal keratinocytes under both normoxic (21% O2) and hypoxic (1% O2) environments. Results revealed that local application of MACF provided 233.8 ± 9.9 mmHg oxygen partial pressure after 2 h then maintained equilibrium oxygen levels that were approximately 17 mmHg partial pressure greater than untreated controls. Cell culture experiments showed that MACF oxygenating gels improved cellular functions involved in wound healing such as cell metabolism, total DNA synthesis and cell migration under hypoxia in both fibroblasts and keratinocytes. Adenosine triphosphate (ATP) quantification also revealed that MACF treatments improved cellular ATP levels significantly over controls under both normoxia and hypoxia (p<0.005). In total, these studies provide new data to indicate that supplying local oxygen via MACF hydrogels under hypoxic environments improves key wound healing cellular functions.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Next, they were saturated with oxygen by bubbling the solution with pure gaseous O 2 to MACF gels for 30 min at 5 PSI as previously described. 25 …”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Fluorinated Methacrylamide Chitosan Hydrogels Enhance Cellular Wound Healing Processes

2017

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Functionalization of Graphene with Molecules and/or Nanoparticles for Advanced Applications

Scaffaro

Riccobono

Pibiri

2019

Handbook of Graphene

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Fluorinated Chitosan Microgels to Overcome Internal Oxygen Transport Deficiencies in Microtissue Culture Systems

2020

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candidates, and in the past preclinical animal models have been employed that do not necessarily provide results that translate into humans. [2] It has been shown that beginning drug discovery in human cell-based platforms can decrease failure rates. [3] This is only one illustrative example highlighting the usefulness of humanized cell-based platforms in the study of human health and disease. Emerging technologies such as microphysical systems, organs-on-a-chip, 3D bioprinting, and cell spheroid/organoids offer tantalizing utility for medicine. [4] Human cell-based organoids specifically present more realistic and physiologically relevant models, [5] and provide significant utility for personalized disease modelling, drug screening, and even regenerative medicine research. [3] Organoids are miniaturized and simplified versions of organs typically derived from stem cells. They possess threedimensional microanatomy with several organ-specific differentiated and progenitor cell types. Multi-cellular spheroids present a simplified version of organoids using one organ-specific cell-type to reduce the overall complexity and are often the preferred starting point for organoid research. [6] A persistent and significant challenge for organoids and spheroids alike is maintaining sufficient oxygen perfusion to create large anatomically relevant functional tissues in vitro. [7] Past attempts to artificially improve oxygen transport includes artificial microvessels, direct fluid perfusion, and oxygen vesicles for oxygen transport. [8] Each of these techniques faces their own challenges, and despite the efforts invested in developing them, insufficient oxygenation challenges persist ultimately limiting the size of organoids/ spheroids that can be produced, the ability to maintain them long-term, and consequently their physiologic relevance to medical applications. In this study we report a novel strategy to enhance oxygen transport in 3D in vitro human cell cultures using chitosan-PFC oxygenating microgels added to cell aggregate spheroids, enabling the ability to tune local spheroid oxygenation to enhance spheroid utility. One important advantage of this approach is that it combines several mechanisms to boost oxygen transport from the surrounding environment. First, Poor oxygen transport is a major obstacle currently for 3D microtissue culture platforms, which at this time cannot be grown large enough to be truly physio logically relevant and replicate adult human organ functions. To overcome internal oxygen transport deficiencies, oxygenating microgels are formed utilizing perfluorocarbon (PFC) modified chitosan and a highly scalable water-in-oil miniemulsion method. Microgels that are on the order of a cell diameter (≈10 µm) are formed allowing them to directly associate with cells when included in 3D spheroid culture, while not being internalized. The presence of immobilized PFCs in these microgels allows for enhancement and tuning of oxygen transport when incorporated into cultured microtissues. As such, it is demonstra...

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Fluorinated methacrylamide chitosan hydrogels enhance collagen synthesis in wound healing through increased oxygen availability

Cited by 83 publications

References 59 publications

Fluorinated Methacrylamide Chitosan Hydrogels Enhance Cellular Wound Healing Processes

Fluorinated Methacrylamide Chitosan Hydrogels Enhance Cellular Wound Healing Processes

Functionalization of Graphene with Molecules and/or Nanoparticles for Advanced Applications

Fluorinated Chitosan Microgels to Overcome Internal Oxygen Transport Deficiencies in Microtissue Culture Systems

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