Theranostics 2022; 12(1):18-34. doi:10.7150/thno.67148 This issue Cite

Research Paper

Acceleration of chronic wound healing by bio-inorganic polyphosphate: In vitro studies and first clinical applications

Hadrian Schepler1, Meik Neufurth2, Shunfeng Wang2, Zhengding She3, Heinz C. Schröder4, Xiaohong Wang2✉, Werner E.G. Müller2✉

1. Department of Dermatology, University Clinic Mainz, Langenbeckstr. 1, D-55131 Mainz, Germany.
2. 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.
3. Shenzhen Lando Biomaterials Co., Ltd., Building B3, Unit 2B-C, China Merchants Guangming Science Park, Guangming District, Shenzhen 518107, China.
4. NanotecMARIN GmbH, Mühlstr. 19, D-55218 Ingelheim am Rhein, Germany.

Citation:
Schepler H, Neufurth M, Wang S, She Z, Schröder HC, Wang X, Müller WEG. Acceleration of chronic wound healing by bio-inorganic polyphosphate: In vitro studies and first clinical applications. Theranostics 2022; 12(1):18-34. doi:10.7150/thno.67148. https://www.thno.org/v12p0018.htm
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Abstract

Graphic abstract

The healing of chronic wounds is impaired by a lack of metabolic energy. In previous studies, we showed that physiological inorganic polyphosphate (polyP) is a generator of metabolic energy by forming ATP as a result of the enzymatic cleavage of the high-energy phosphoanhydride bonds of this polymer. Therefore, in the present study, we investigated whether the administration of polyP can substitute for the energy deficiency in chronic wound healing.

Methods: PolyP was incorporated into collagen mats and applied in vitro and to patients in vivo.

Results: (i) In vitro studies: Keratinocytes grown in vitro onto the polyP/collagen mats formed long microvilli to guide them to a favorable environment. HUVEC cells responded to polyP/collagen mats with an increased adhesion and migration propensity as well as penetration into the mats. (ii) In vivo - human clinical studies: In a “bench to bedside” process these promising in vitro results were translated from the laboratory into the clinic. In the proof-of-concept application, the engineered polyP/collagen mats were applied to chronic wounds in patients. Those mats impressively accelerated the re-epithelialization rate, with a reduction of the wound area to 65% after 3 weeks and to 36.6% and 22.5% after 6 and 9 weeks, respectively. Complete healing was achieved and no further treatment was necessary. Biopsy samples from the regenerating wound area showed predominantly myofibroblasts. The wound healing process was supported by the use of a polyP containing moisturizing solution.

Conclusion: The results strongly recommend polyP as a beneficial component in mats for a substantial healing of chronic wounds.

Keywords: Inorganic polyphosphate, Nanoparticles, Chronic wounds, Compressed collagen, Re-epithelialization


Citation styles

APA
Schepler, H., Neufurth, M., Wang, S., She, Z., Schröder, H.C., Wang, X., Müller, W.E.G. (2022). Acceleration of chronic wound healing by bio-inorganic polyphosphate: In vitro studies and first clinical applications. Theranostics, 12(1), 18-34. https://doi.org/10.7150/thno.67148.

ACS
Schepler, H.; Neufurth, M.; Wang, S.; She, Z.; Schröder, H.C.; Wang, X.; Müller, W.E.G. Acceleration of chronic wound healing by bio-inorganic polyphosphate: In vitro studies and first clinical applications. Theranostics 2022, 12 (1), 18-34. DOI: 10.7150/thno.67148.

NLM
Schepler H, Neufurth M, Wang S, She Z, Schröder HC, Wang X, Müller WEG. Acceleration of chronic wound healing by bio-inorganic polyphosphate: In vitro studies and first clinical applications. Theranostics 2022; 12(1):18-34. doi:10.7150/thno.67148. https://www.thno.org/v12p0018.htm

CSE
Schepler H, Neufurth M, Wang S, She Z, Schröder HC, Wang X, Müller WEG. 2022. Acceleration of chronic wound healing by bio-inorganic polyphosphate: In vitro studies and first clinical applications. Theranostics. 12(1):18-34.

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