Combination of advanced techniques of 3D printing, electrospinning and spin-coating with the support of active substances (analgesics, cells, growth factors) for development of novel materials for effective chronic wound care

Reference number

ARRS-RPROJ-JR-Prijava/2016-I/753

Partnering organisations

Univesity in Maribor, Faculty of mechanical engineering

Univerza v Mariboru Logotip

Coordination

Tina Maver (project leader) 

Duration

1.5.2017―30.4.2019 

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Abstract:

This project goes beyond the state of the art in various fields by combining the most advanced techniques in materials science (3D printing of biomaterials, production of nanofibers by electrospinning, and production of model films by spin coating), sophisticated approaches in pharmaceutical technology (with the inclusion of analgesics and growth factors), and following recent trends in biomedical applications (advanced in vitro release testing, assessment of wound healing physiology, and testing with human functional cells). Such an interdisciplinary approach led to significant insights in the development of biomaterials for wound care as well as in the field of controlled release of drugs.

Scaffolds for wound care were fabricated by 3D (bio)printing of the currently most promising materials for wound care that have been shown to have a beneficial effect on healing (alginate, carboxymethylcellulose, polycaprolactone, etc.). Keratinocytes (epidermis) and fibroblasts (dermis) from human skin were then incorporated in-situ. The effect of these materials on cell viability was studied after up to one month. An additional layer of nanofiber network was applied to the surface of the 3D scaffold, which was produced by electrospinning (laboratory single-needle or pilot-needle electrospinning). By incorporating active ingredients into the nanofiber network, we added another functionality to the new material, namely pharmacotherapeutic activity (pain relief either by the nonsteroidal anti-inflammatory drug (NSAID) diclofenac or by local anesthetics (LA) lidocaine and bupivacaine). At the same time, the 3D constructs thus produced were also able to influence the healing process at the molecular level (e.g., proliferation of fibroblasts, collagen deposition, angiogenesis, etc.), which was achieved by adding growth factors such as platelet-derived growth factor (PDGF) and fibroblastic growth factor (FGF). The electrospun nanofibers have a positive effect on the healing process on three levels: 1) they relieve pain (through active pharmacotherapy), which promotes the healing process through stress reduction, 2) the growth factors have a direct positive effect on the healing process, and 3) through the similar structure and morphology of the electrospun nanofiber network with the native extracellular matrix (ECM) of the skin. A systematic characterization of the fabricated materials was performed using different methods.

Finally, the safety and efficacy of the fabricated materials were investigated using cell cultures from human skin. The verification and understanding of the processes and interactions between the polymeric materials and the incorporated active components, as well as the polymeric materials and their physiological environment in the wound, was achieved through the fabrication of thin model films made by spin coating of the same material compositions used in the 3D-printed materials. AFM and IR methods were used to also characterize the model films in simulated physiological environments of the wound (simulating conditions in wounds).

Although this project was at its core a basic science project, it was nevertheless aimed at developing patentable advanced materials that could significantly improve the quality of life of patients suffering from chronic wounds in the future. At the same time, it provided a platform for testing other related materials with potential in the field of regenerative medicine.

Financing, programme, call

Public Call for co-financing of research projects in 2017) 

Basic Postdoc Project 

Publications

Polysaccharide-Based Bioink Formulation for 3D Bioprinting of an In Vitro Model of the Human Dermis, Nanomaterials, 2020

Needleless electrospun carboxymethyl cellulose/polyethylene oxide mats with medicinal plant extracts for advanced wound care applications, Cellulose, 2020

Impact of growth factors on wound healing in polysaccharide blend thin films, Applied Surface Science, 2019

Development of multifunctional 3D printed bioscaffolds from polysaccharides and NiCu nanoparticles and their application, Applied Surface Science, 2019

Polysaccharide thin solid films for analgesic drug delivery and growth of human skin cells, Frontiers in chemistry, 2019

Systematic evaluation of a diclofenac-loaded carboxymethyl cellulose-based wound dressing and its release performance with changing ph and temperature, AAPS PharmSciTech, 2019

A multifunctional electrospun and dual nano-carrier biobased system for simultaneous detection of pH in the wound bed and controlled release of benzocaine, Cellulose, 2018

Combining 3D printing and electrospinning for preparation of pain-relieving wound-dressing materials, Journal of Sol-Gel Science and Technology, 2018

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