Cells and tissues are an essential part of many medicinal experiments – either as main players in novel therapies or as a waste material accompanying medicinal intervention (or both). Regardless of their role in therapy they can be collected and stored by biobanks. We present the example of a very effective pathway from a clinical trial of Advanced Therapy Investigational Medicinal Products (ATIMP) containing adipose-derived stem cells towards patent application embracing a cell-containing dressing for treating hard-to-heal wounds. The medicinal area of the clinical trial and the dressing application are completely different (are not related to each other). The point is, that excess cells intended for use in the therapy were collected in the biobank and used in the experiments to design innovative ADSC-enriched wound care products.
With this example, we present a very effective pathway of using the biological material with the biobank in a central part of it.
The ADSCs were obtained from healthy donors' subcutaneous fat after informed consent (No KB/887/13, KB/887A/13 and KB/1097/17), then subjected to preparation of ATIMP for the clinical trial under GMP regime. The excess cells were transferred to the biobank of the Medical University of Warsaw and used for development of the innovative dressing. ADSCs were cultured in complete NutriStem medium, then seeded on 4 commercially available wound dressings dedicated for diabetic foot ulcer treatment: Tisseel Lyo, UrgoTul, Mepilex, and MepitelOne. Successful cell attachment to dressings was confirmed with Presto Blue proliferation test, fluorescent staining, scanning electron microscope (SEM), and light microscope (LM) observations. Obtained ADSC-enriched wound dressings were tested for proficiency for wound healing process acceleration in scar tests with fibroblasts from healthy donors (nHF). Additionally, freeze-thaw cycle was performed to confirm the feasibility of long-term storage.
Both SEM and LM observations confirmed the presence of ADSCs on or in the wound dressings. Presto Blue assay and fluorescent staining showed that ADSC maintain their viability up to 21 days of culture on selected wound dressings. After freezing-thawing cycle ADSC-enriched wound dressings were observed in LM. Only Mepilex did not maintain ADSCs viability throughout the freezing procedure. In the scar test assay, all ADSC-enriched wound dressings accelerated nHF scar closure rate compared to control: UrgoTul–10,30% (starting scar surface), Mepilex–1,32%; Tisseel Lyo–11,78%; MepitelOne–full closure of the scar; no dressing control–20,33%.
In summary, the most promising base for ADSC-enriched ATIMP development were two of the selected commercially available dressings – MepitelOne and UrgoTul. Both setups accelerated wound healing in vitro and maintained ADSC viability throughout the freezing-thawing cycle. Those are the key features regarding cell-based dressing for hard-to-heal wound treatment. Therefore, the ADSC complexes with MepitelOne and UrgoTul have been subjected to a patent procedure, which resulted in an international patent application – “A dressing for treating hard-to-heal wounds and a process for the manufacture thereof” (PCT application number PCT/PL2021/050068).
This work was supported by NCBR, grant no. STRATEGMED2/267976/13/NCBR/2015 and MNSW, grant no. DIR/WK/2017/2018/01-1.