Karin Stana Kleinschek

Nanofibrous polysaccharide hydroxyapatite composites with biocompatibility against human osteoblasts

Regenerative medicine has a high demand for defined scaffold materials that promote cell growth, stabilize the tissue during maturation and provide a proper three dimensional structure that allows the exchange of nutrients. In many instances nanofiber composites have already shown their potential for such applications. This work elaborates the development of polysaccharide based nanofibers with integrated hydroxyapatite nanoparticles. A detailed study on the formation of electrospun nanofibres from aqueous mixtures of carboxymethyl cellulose polyethylene oxide was performed. The influence of different processing conditions and spinning solution properties using a nozzle-less electrospinning device was systematically studied. Optimized parameters were used to incorporate hydroxyapatite nanoparticles into the fibers. Nanofibers were additionally hydrophobized with alkenyl succinic anhydride (ASA) to render them insoluble in water. The nanofiber webs were thoroughly investigated with respect to morphology, chemical composition and inorganic content. Time dependent biocompatibility testing of the materials with human bone-derived osteoblasts showed no significant reduction in cell viability for the developed materials composed of carboxymethyl cellulose/polyethyleneoxide. Cells grown on hydrophobized materials show similar viability as those grown on a commercial collagen/apatite matrix.

Advanced Wound Care

The world is ageing rapidly. The percentage of older people (aged 60 years and over) worldwide increased from 9.2 % in 1990 to 11.7 % in 2013, and will reach 21.1 % by 2050 (Wound Management in An

Other Solutions to Achieve Desired Wound Healing Characteristics

18.5 billion+ worldwide market in 2021, 2015 [1]). That means the number of elderly is expected to more than double, from 841 million people in 2013 to more than 2 billion in 2050 (Fig. 1a). The ageing is connected strongly with the higher incidence of wounds. Exponential growth of older people is, therefore, parallel, followed by exponential growth of the wound management market (Fig. 1b).

Tissue Engineering Products

The variety of wound types has resulted in a wide range of wound care approaches, which are fast developing due to numerous researches. The integration of technological advances with understanding of the complex cellular and biochemical mechanisms of wound healing has led to the development of various advanced wound healing modalities, such as bioengineered skin and tissue equivalents, Negative Pressure Wound Therapy (NPWT), use of plasma, photochemical tissue bonding, electroactive material and hyperbaric oxygen therapy.

Safety and Efficiency Testing

The importance and demand for relatively cheap and available skin-replacement products encouraged many research groups worldwide to focus on creating biomaterials for skin substitution [1]. Engineered tissues that not only close wounds, but also stimulate the regeneration of the dermis, would provide a significant benefit in human wound healing [2].

Polysaccharide Based Wound Care Materials

The biocompatibility/cytotoxicity of materials intended for biomedical applications are always of utter importance (Danoux et al. in Acta Mater 17:1–15, 2015 [1], Yan et al. in Acta Biomater 12:227–241, 2015 [2]) Although the main objective of such testing is mostly related to assessment of the respective material safety and efficiency, functional testing of materials in relation to their targeted use is also needed to be considered. The main objective of the approach towards such testing is, therefore, not only related to the assessment of the specific materials’ biocompatibility with desired cells, but also the execution of the test as similar to the physiological application as possible (Naranda et al. in Sci Rep 6:28695, 2016 [3], Finsgar et al. in Sci Rep 6:26653, 2016 [4]). Related to this, the effect of possibly released toxic degradation products that could hinder cell growth can be determined, as well as possible local overdoses of respective drugs, which are often part of tested formulations, could be assessed, since these could also potentially harm the growing cells (Finsgar et al. in Sci Rep 6:26653, 2016[4]). Another related testing approach is to determine the respective formulation influence on the cell growth in comparison with different control samples (Naranda et al. in Sci Rep 6:28695, 2016 [3], Gradisnik et al. in Global Spine J 6:WST014, 2016 [5], Velnar et al. in Global Spine J 6:WST019, 2016 [6]). The following chapter will, therefore, be composed of two main parts. The first will review briefly some of the most used testing approaches in general (mostly according to the related ISO Standard—ISO 10993), while the second part will review and describe some of possible modifications of such standard approaches to get the best possible overview of the respective materials’ safety and efficiency for a specific purpose.

Emerging Techniques in the Preparation of Wound Care Products

Polysaccharides are finding an increasing number of applications in medical and pharmaceutical fields thanks to their biodegradability, biocompatibility, and, in some cases, bioactivity (Liu et al. in Cellulose 23:3129–3143, 2016 [1]). Since they also play an important role in the field of Wound Healing, the second chapter will be dedicated entirely to them.

Active Substances for Acceleration of Wound Healing

Numerous methods have been utilised to fabricate scaffolds with varying mechanical properties, suitable also to be used in wound care, for instance, conventional techniques, which include solvent casting and particle leaching, freeze-drying, thermally induced phase separation, gas foaming, and the sol–gel technique [1].

Novel electrospun fibers with incorporated commensal bacteria for potential preventive treatment of the diabetic foot

Modern approaches that influence wound healing actively to achieve rapid and complete healing of chronic wounds are in demand. There is a still unmet need for novel strategies to achieve expeditious wound healing because of the enormous financial burden worldwide. The next chapters, therefore, review some of the most daring novel solutions that could speed up the uptake of novel technologies into wound care, as well as some important advancements in this field that shall influence the modern wound treatment in the near future. Some aspects of advanced wound dressings to go beyond the state-of-the-art in this field, are shown in Fig. 4.1.

Effect of different surface active polysaccharide derivatives on the formation of ethyl cellulose particles by the emulsion-solvent evaporation method

AIMnA novel electrospun biocompatible nanofibrous material loaded with commensal bacteria for potential preventive treatment of the diabetic foot was developed.nnnMATERIALS & METHODSnTwo biocompatible polymers (carboxymethylcellulose and polyethylene oxide) were combined with a bacterium isolate from the skin located between the toes of a healthy adult (identified using a matrix-assisted laser desorption/ionization mass spectrometry-based method as a strain of Staphylococcus epidermidis). Higher bacteria loads in the material were assured through their encapsulation in polyethylenimine. The nanofibrous material was characterized using scanning electron microscopy, zeta-potential measurements and through evaluation of cell growth and viability.nnnRESULTS & DISCUSSIONnnanometer formation was confirmed using scanning electron microscopy, while the zeta-potential measurements revealed successful bacteria encapsulation. Viable and sufficiently growing cells were confirmed prior and after their incorporation.nnnCONCLUSIONnThe prepared materials were proven suitable to deliver viable commensal bacteria in a comparable share to the Staphylococcaceae in the foot microbiome making this approach promising for preventive diabetic foot treatment.