Acceleration of Wound Healing through Amorphous Calcium Carbonate, Stabilized with High-Energy Polyphosphate
Shunfeng Wang,
Meik Neufurth,
Hadrian Schepler,
Rongwei Tan,
Zhending She,
Bilal Al-Nawas,
Xiaohong Wang,
Heinz C. Schröder,
Werner E. G. Müller
Affiliations
Shunfeng Wang
ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany
Meik Neufurth
ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany
Hadrian Schepler
Department of Dermatology, University Clinic Mainz, Langenbeckstr. 1, D-55131 Mainz, Germany
Rongwei Tan
Shenzhen Lando Biomaterials Co., Ltd., Building B3, Unit 2B-C, China Merchants Guangming Science Park, Guangming District, Shenzhen 518107, China
Zhending She
Shenzhen Lando Biomaterials Co., Ltd., Building B3, Unit 2B-C, China Merchants Guangming Science Park, Guangming District, Shenzhen 518107, China
Bilal Al-Nawas
Clinic for Oral and Maxillofacial Surgery and Plastic Surgery, University Medical Center of the Johannes Gutenberg University, Augustusplatz 2, D-55131 Mainz, Germany
Xiaohong Wang
ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany
Heinz C. Schröder
ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany
Werner E. G. Müller
ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany
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.
