The expression of sonic hedgehog in diabetic wounds following treatment with poly(methacrylic acid-co-methyl methacrylate) beads

Fitzpatrick, Lindsay E.; Lisovsky, Alexandra; Sefton, Michael V.

doi:10.1016/j.biomaterials.2012.04.008

Cited by 29 publications

(41 citation statements)

References 67 publications

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“…Previously, MAA beads were found to increase vascularization in both small and large wounds at day 7 in diabetic males [5,6]. Likewise, MAA beads increased the vessel density in large wounds in non-diabetic transgenic males at day 7 (p ¼ 0.001) (Fig.…”

Section: The Effect Of Maa Beads On Vessel Densitymentioning

confidence: 65%

“…MAA beads were previously studied in diabetic (BKS.Cg-mþ/þ Lepr db /J; db/db) mice in both large (15 mm Â 15 mm) and small (7.5 mm Â 7.5 mm) wounds [5,6]. Large wounds were chosen as the model in the present study, since it was thought that smaller wounds would heal too quickly on their own in non-diabetic animals.…”

Section: Effect Of Maa Beads In the Non-diabetic Wound Healing Model mentioning

confidence: 99%

“…7 (males), n ¼ 10 (females); ***p 0.001. (PDGFb) -associated with the Shh pathway and previously shown to be modulated by MAA beads to some degree either in vivo [6] or in vitro [8,9] were investigated in males. These genes were not significantly modulated by MAA beads within the wound tissue at days 4 and 7 (Supplementary information, Fig.…”

Section: The Effect Of Maa Beads On Shh Signaling In Granulation Tissuementioning

confidence: 99%

“…[1e4]]. Earlier studies in diabetic animals demonstrated the therapeutic effect of methacrylic acid (MAA)-based biomaterials in wound healing [5,6]. Poly(methacrylic acid-co-methyl methacrylate) (MAA) beads increased vessel formation and subsequently improved wound repair (e.g., degree of wound closure and epithelial gap) [5].…”

Section: Introductionmentioning

confidence: 99%

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Shh pathway in wounds in non-diabetic Shh-Cre-eGFP/Ptch1-LacZ mice treated with MAA beads

Lisovsky

Sefton

2016

Biomaterials

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Section: The Effect Of Maa Beads On Vessel Densitymentioning

confidence: 65%

Section: Effect Of Maa Beads In the Non-diabetic Wound Healing Model mentioning

confidence: 99%

Section: The Effect Of Maa Beads On Shh Signaling In Granulation Tissuementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Shh pathway in wounds in non-diabetic Shh-Cre-eGFP/Ptch1-LacZ mice treated with MAA beads

Lisovsky

Sefton

2016

Biomaterials

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“…This study investigated the effects of a methacrylic acid (MAA) copolymer on cells because these polymers have been shown to promote vascular regenerative responses in vivo (9,10), but the mechanism behind this response is unknown (11)(12)(13). Previous studies showed that 45% poly(MAA-co-methyl methacrylate [MM]) copolymer beads promoted vascularization and improved wound healing in diabetic mice (10) or with skin grafts in rats (9).…”

mentioning

confidence: 99%

Unbiased phosphoproteomic method identifies the initial effects of a methacrylic acid copolymer on macrophages

Chamberlain

Wells

Lisovsky

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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An unbiased phosphoproteomic method was used to identify biomaterial-associated changes in the phosphorylation patterns of macrophage-like cells. The phosphorylation differences between differentiated THP1 (dTHP1) cells treated for 10, 20, or 30 min with a vascular regenerative methacrylic acid (MAA) copolymer or a control methyl methacrylate (MM) copolymer were determined by MS. There were 1,470 peptides (corresponding to 729 proteins) that were differentially phosphorylated in dTHP1 cells treated with the two materials with a greater cellular response to MAA treatment. In addition to identifying pathways (such as integrin signaling and cytoskeletal arrangement) that are well known to change with cell–material interaction, previously unidentified pathways, such as apoptosis and mRNA splicing, were also discovered.

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Cell Interactions with Vascular Regenerative MAA‐Based Materials in the Context of Wound Healing

Lisovsky

Chamberlain

Wells

et al. 2015

Adv Healthcare Materials

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In diabetic patients the development of chronic non-healing wounds is a common complication. A methacrylic acid-based biomaterial is a vascular regenerative material that enhances diabetic healing without the use of cells or growth factors. The bioactive nature of this material is thought to be associated with its anionic charge or surface chemistry. Contact between the methacrylic acid-based biomaterial and tissue begins with protein (including complement) adsorption and is followed by interaction of the biomaterial with resident and infiltrating cells in the wound bed (e.g., macrophages and endothelial cells). This results in changes to their surface receptors to activate phosphorylation cascades that lead to differential activation of signalling pathways such as those involving osteopontin and sonic hedgehog. These changes modulate the phenotype of the cells in the wound bed, eventually improving vessel formation and wound healing. Understanding the molecular and cellular mechanisms will have broad implications for biomaterials, not just the methacrylic acid-based material, and will facilitate the advancement of regenerative biomaterials for diverse applications.

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The expression of sonic hedgehog in diabetic wounds following treatment with poly(methacrylic acid-co-methyl methacrylate) beads

Cited by 29 publications

References 67 publications

Shh pathway in wounds in non-diabetic Shh-Cre-eGFP/Ptch1-LacZ mice treated with MAA beads

Shh pathway in wounds in non-diabetic Shh-Cre-eGFP/Ptch1-LacZ mice treated with MAA beads

Unbiased phosphoproteomic method identifies the initial effects of a methacrylic acid copolymer on macrophages

Cell Interactions with Vascular Regenerative MAA‐Based Materials in the Context of Wound Healing

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