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- Title
Acceleration of Wound Healing through Amorphous Calcium Carbonate, Stabilized with High-Energy Polyphosphate.
- Authors
Wang, Shunfeng; Neufurth, Meik; Schepler, Hadrian; Tan, Rongwei; She, Zhending; Al-Nawas, Bilal; Wang, Xiaohong; Schröder, Heinz C.; Müller, Werner E. G.
- Abstract
Amorphous calcium carbonate (ACC), precipitated in the presence of inorganic polyphosphate (polyP), has shown promise as a material for bone regeneration due to its morphogenetic and metabolic energy (ATP)-delivering properties. The latter activity of the polyP-stabilized ACC ("ACC∙PP") particles is associated with the enzymatic degradation of polyP, resulting in the transformation of ACC into crystalline polymorphs. In a novel approach, stimulated by these results, it was examined whether "ACC∙PP" also promotes the healing of skin injuries, especially chronic wounds. In in vitro experiments, "ACC∙PP" significantly stimulated the migration of endothelial cells, both in tube formation and scratch assays (by 2- to 3-fold). Support came from ex vivo experiments showing increased cell outgrowth in human skin explants. The transformation of ACC into insoluble calcite was suppressed by protein/serum being present in wound fluid. The results were confirmed in vivo in studies on normal (C57BL/6) and diabetic (db/db) mice. Topical administration of "ACC∙PP" significantly accelerated the rate of re-epithelialization, particularly in delayed healing wounds in diabetic mice (day 7: 1.5-fold; and day 13: 1.9-fold), in parallel with increased formation/maturation of granulation tissue. The results suggest that administration of "ACC∙PP" opens a new strategy to improve ATP-dependent wound healing, particularly in chronic wounds.
- Subjects
WOUND healing; CALCIUM carbonate; TOPICAL drug administration; GRANULATION tissue; CHRONIC wounds &; injuries; BONE regeneration; SKIN injuries
- Publication
Pharmaceutics, 2023, Vol 15, Issue 2, p494
- ISSN
1999-4923
- Publication type
Article
- DOI
10.3390/pharmaceutics15020494