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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 Wang^2✉, Werner E.G. Müller^2✉

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.

✉ Corresponding authors: Prof. Dr. W.E.G. Müller, Prof. Dr. X.H. Wang, ERC Advanced Investigator Grant Research Group at Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany. Tel.: +49 6131-39-25910; Fax: +49 6131-39-25243; E-mail: wmuellerde (Prof. Dr. W.E.G. Müller); wang013de (Prof. Dr. X.H. Wang). More

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

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