Scarless healing of oral mucosa is characterized by faster resolution of inflammation and control of myofibroblast action compared to skin wounds in the red Duroc pig model

Mak, Karen; Manji, Aleem; Gallant‐Behm, Corrie L.; Wiebe, Colin; Hart, David A.; Larjava, Hannu; Häkkinen, Lari

doi:10.1016/j.jdermsci.2009.09.005

Cited by 183 publications

(221 citation statements)

References 34 publications

Supporting

Mentioning

206

Contrasting

Unclassified

Order By: Relevance

“…[6] Besides, a much larger population is badly in need of scar reduction therapies. [7,8] Although recent research has elucidated many factors and details that contribute to scar formation, [6,[9][10][11] www.advancedsciencenews.com www.advhealthmat.de factor (PDGF), TGF-β, vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and epidermal growth factor (EGF)). [29,30] Thus, macrophages may either induce tissue destruction (M1) or initiate regeneration (M2).…”

Section: Introductionmentioning

confidence: 99%

Pro‐Regenerative Hydrogel Restores Scarless Skin during Cutaneous Wound Healing

Sun

2017

Adv Healthcare Materials

View full text Add to dashboard Cite

The transformation of fibrotic healing process to regenerative one has great potential to fully restore wounded skin. The M2 macrophage phenotype promotes constructive tissue remodeling and instructs tissue repair in a regenerative manner. It is hypothesized that hydrogels that can establish robustness of endogenous cells to regulate M2 phenotype will promote constructive dermal remodeling. Toward this end, a series of dextran‐based bioabsorbable hydrogels are developed and self‐crosslinkable dextran‐isocyanatoethyl methacrylate‐ethylamine (DexIEME) is identified as the potential scaffold. The initial screening study revealed that DexIEME has superior biocompatibility in varying concentrations. Although DexIEME brings about low proinflammatory responses, it promotes M2 macrophage phenotype. Then the optimized hydrogel formulation is tested for acute skin injuries using both murine and porcine models. Preliminary data demonstrated that the innovative DexIEME hydrogel promotes complete skin regeneration with hair regrowth on pre‐existing scars, while untreated scars remain intact. Preclinical studies further demonstrated that the DexIEME hydrogel regenerated perfect skin during deep porcine wound healing. Overall, the approach to investigate immune‐modulated hydrogels yields pro‐regenerative DexIEME hydrogel, which may lead to greater clinical success in treating deep dermal injury and attenuating scar formation.

show abstract

Section: Introductionmentioning

confidence: 99%

Pro‐Regenerative Hydrogel Restores Scarless Skin during Cutaneous Wound Healing

Sun

2017

Adv Healthcare Materials

View full text Add to dashboard Cite

show abstract

“…142 Myofibroblasts persist in fibrotic conditions and pathological scars, where they continue to produce matrix. 141 However, the number of myofibroblasts in the oral mucosal wounds, which heal with minimal scarring, is higher than in skin wounds, 143 suggesting that the presence of myofibroblasts per se does not predict scarring or fibrosis.…”

mentioning

confidence: 99%

Integrins in Wound Healing

Koivisto

Heino

Häkkinen

et al. 2014

Advances in Wound Care

Self Cite

181

154

View full text Add to dashboard Cite

“…In general, oral wounds heal more rapidly and with better final scar quality than skin wounds (Engeland et al, 2006; Kiecolt‐Glaser et al, 1995; Larjava et al, 2011; Mak et al, 2009). In this study we characterized and compared the mode of action of SS and GS that were cultured under identical procedures and are fully compliant with the current European regulations for ATMPs.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, gingiva not only heals faster than skin, but also heals with negligible final scarring (Larjava et al, 2011; Mak et al, 2009; Szpaderska, Zuckerman, & DiPietro, 2003), although it is currently unknown why. HGF has been shown to have an anti‐fibrotic effect and it also acts as a mitogen and motogen (Crestani et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…In this study we identified the mode of action in vitro of the second generation SS and GS and in doing so can describe important intrinsic differences between SS and GS. These tissue‐specific differences may explain in part the superior quality of wound healing generally observed in oral mucosa compared with skin (Engeland, Bosch, Cacioppo, & Marucha, 2006; Kiecolt‐Glaser, Marucha, Malarkey, Mercado, & Glaser, 1995; Larjava et al, 2011; Mak et al, 2009). …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Comparison of advanced therapy medicinal product gingiva and skin substitutes and their in vitro wound healing potentials

Boink

Roffel

Breetveld

et al. 2017

J Tissue Eng Regen Med

View full text Add to dashboard Cite

Skin and oral mucosa substitutes are a therapeutic option for closing hard‐to‐heal skin and oral wounds. Our aim was to develop bi‐layered skin and gingiva substitutes, from 3 mm diameter biopsies, cultured under identical conditions, which are compliant with current European regulations for advanced therapy medicinal products. We present in vitro mode of action methods to (i) determine viability: epithelial expansion, proliferation (Ki‐67), metabolic activity (MTT assay); (ii) characterize skin and gingiva substitutes: histology and immunohistochemistry; and (iii) determine potency: soluble wound healing mediator release (enzyme‐linked immunosorbent assay). Both skin and gingiva substitutes consist of metabolically active autologous reconstructed differentiated epithelium expanding from the original biopsy sheet on a fibroblast populated connective tissue matrix (donor dermis). Gingival epithelium expanded 1.7‐fold more than skin epithelium during the 3 week culture period. The percentage of proliferating Ki‐67‐positive cells located in the basal layer of the gingiva substitute was >1.5‐fold higher than in the skin substitute. Keratins 16 and 17, which are upregulated during normal wound healing, were expressed in both the skin and gingiva substitutes. Notably, the gingiva substitute secreted higher amounts of key cytokines involved in mitogenesis, motogenesis and chemotaxis (interleukin‐6 > 23‐fold, CXCL8 > 2.5‐fold) as well as higher amounts of the anti‐fibrotic growth factor, hepatocyte growth factor (>7‐fold), compared with the skin substitute. In conclusion, while addressing the viability, characterization and potency of the tissue substitutes, important intrinsic differences between skin and gingiva were discovered that may explain in part the superior quality of wound healing observed in the oral mucosa compared with skin.

show abstract

Scarless healing of oral mucosa is characterized by faster resolution of inflammation and control of myofibroblast action compared to skin wounds in the red Duroc pig model

Cited by 183 publications

References 34 publications

Pro‐Regenerative Hydrogel Restores Scarless Skin during Cutaneous Wound Healing

Pro‐Regenerative Hydrogel Restores Scarless Skin during Cutaneous Wound Healing

Integrins in Wound Healing

Comparison of advanced therapy medicinal product gingiva and skin substitutes and their in vitro wound healing potentials

Contact Info

Product

Resources

About