A recombinant signalling‐selective activated protein C that lacks anticoagulant activity is efficacious and safe in cutaneous wound preclinical models.
Various preclinical and clinical studies have demonstrated the robust wound healing capacity of the natural anticoagulant activated protein C (APC). A bioengineered APC variant designated 3K3A‐APC retains APC's cytoprotective cell signalling actions with <10% anticoagulant activity. This study was a...
| Publicado en: | Wound Repair & Regeneration Vol. 32; no. 1; pp. 90 - 104 |
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| Autores principales: | , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Jan/Feb2024
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=175055566&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 175055566 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 10671927 DPV jtl: Wound Repair & Regeneration issn: 10671927 maglogo: Y pubinfo: dt: Jan/Feb2024 vid: 32 iid: 1 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 175055566 174557461 175055566 175055566 10.1111/wrr.13148 175055566 ppf: 90 ppct: 14 formats: fmt: – @attributes: type: T – @attributes: type: C – @attributes: type: P tig: atl: A recombinant signalling‐selective activated protein C that lacks anticoagulant activity is efficacious and safe in cutaneous wound preclinical models. aug: au: Zhao, Ruilong Xue, Meilang Lin, Haiyan Smith, Margaret Liang, Helena Weiler, Hartmut Griffin, John H. Jackson, Christopher J. affil: Sutton Laboratory, Kolling Institute of Medical Research, Sydney New South Wales,, Australia sug: subj: Skin Injuries Wounds and Injuries Drug Therapy Recombinant Proteins Therapeutic Use Anticoagulants Therapeutic Use Drug Efficacy Evaluation Wound Healing Evaluation Drug Evaluation, Preclinical Wound Care Human Funding Source Animal Studies Mice Swine Matrix Metalloproteinases Fibroblasts Histological Techniques Models, Biological Cell Culture Techniques Comparative Studies Models, Statistical Anticoagulants Administration and Dosage Administration, Topical ab: Various preclinical and clinical studies have demonstrated the robust wound healing capacity of the natural anticoagulant activated protein C (APC). A bioengineered APC variant designated 3K3A‐APC retains APC's cytoprotective cell signalling actions with <10% anticoagulant activity. This study was aimed to provide preclinical evidence that 3K3A‐APC is efficacious and safe as a wound healing agent. 3K3A‐APC, like wild‐type APC, demonstrated positive effects on proliferation of human skin cells (keratinocytes, endothelial cells and fibroblasts). Similarly it also increased matrix metollaproteinase‐2 activation in keratinocytes and fibroblasts. Topical 3K3A‐APC treatment at 10 or 30 μg both accelerated mouse wound healing when culled on Day 11. And at 10 μg, it was superior to APC and had half the dermal wound gape compared to control. Further testing was conducted in excisional porcine wounds due to their congruence to human skin. Here, 3K3A‐APC advanced macroscopic healing in a dose‐dependent manner (100, 250 and 500 μg) when culled on Day 21. This was histologically corroborated by greater collagen maturity, suggesting more advanced remodelling. A non‐interference arm of this study found no evidence that topical 3K3A‐APC caused either any significant systemic side‐effects or any significant leakage into the circulation. However the female pigs exhibited transient and mild local reactions after treatments in week three, which did not impact healing. Overall these preclinical studies support the hypothesis that 3K3A‐APC merits future human wound studies. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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