Advanced Functional Polymers for Medicine
Authors: Andreas Lendlein, Axel T. Neffe, Christine Jérôme
Journal: Advanced Healthcare Materials (2014)

Applications of polymers in biomedicine are diverse and comprise areas such as cell culture systems, extracorporeal devices or implants.1 Functions and properties of polymers need to address the complex requirements of specific applications,2 which is often challenging to reach with the few materials established in the clinics to date. In order to realize novel fields of applications, chemists, physicists, biologists, and materials scientists are aiming at knowledge-based approaches for biomaterial design of systems based on synthetic3 or biopolymers,4 which would allow to actually fulfill the demands rather than to search for an application suitable to the existing properties and functions of known materials. Implementing new, unexpected, and even seemingly contradictory combinations of functions in polymer-based materials, tailoring their properties, and exploring their potential for biomedical applications are actual topics in this research area. This special issue (SI) of Advanced Healthcare Materials is dedicated to Advanced Functional Polymers for Medicine and was inspired by a conference related to this subject area, which took place in Liège, Belgium, in May 2014, fostering the exchange between the scientific disciplines. The access to biomaterial design and testing as well as the interdisciplinary cooperation becomes exemplarily apparent in the articles of this SI. Three of the articles highlight physical methods and aspects. Schüller-Ravoo et al. describe the formation of microvascular networks by stereolithography of poly(trimethylene carbonate)-based resins. By realizing three-dimensional polymer structures resembling the natural microvasculature, elastic and flexible microstructures were realized displaying a high density of small open channels allowing the perfusion of water at physiological pressures. Human umbilical vein endothelial cells could be cultivated on the structure to give almost confluent layers after three days of culture. In a next step, the diffusion of oxygen through the polymer will need to be improved to realize scaffolds suitable for tissue engineering. Shape-memory micronetworks based on covalent polyester-based networks presented by Friess et al. give access to carriers with a spatially directed active movement upon exposure to an external stimulus. The entropy elastic recovery of the oriented chains in the micronetworks allowed overcoming external forces such as the stability of a metal coating. The system opens the way to study shape-dependent effects of particulate structures in the low μm range. Layer-by-layer (LbL) coating of electron spun nanofibers with polysaccharides was explored by Croisier et al. as means to separate bulk properties of a matrix and their biointerface. By adding a free carboxylic acid groups containing polymer to poly(ε-caprolactone) in the electrospinning process, negative charges can be introduced to the surface allowing the following LbL deposition of chitosan and hyaluronic acid. As the process is modular, basically any polymer for the fibres and polyelectrolytes for the surface deposition can be used. In the presented experiments, a terminal chitosan layer showed better support of keratinocyte growth than the pure fibres. The next three investigations were driven from a more chemical point of view. Sundaramurthy et al. designed an LbL technique for multilayers, in which the interaction of two layers is not based on charged groups, but on hydrogen bonds. For this purpose they employed tannic acid as hydrogen bond donor and three different poly(2-oxazolines) with varying hydrophilicities as hydrogen bond acceptors. The poly(2-oxazolines) were synthesized by microwave-assisted cationic ring-opening polymerization to give polymers with number average molecular weights of 15–17 kDa. Investigation of the thermodynamics of layer growth by isothermal titration calorimetry showed that the deposition of the more hydrophilic poly(2-methyl-2oxazoline) is driven by hydrogen bond formation, while the deposition of the more hydrophobic poly(2-propyl-2- oxazoline) is entropically favored through the release of bound water. As poly(2-oxazolines) are of highest interest for e.g. antifouling coatings, the methodology allows the formation and investigation of important thin layer models. In a Review article, Liu et al. summarize the state-of-the-art for N-vinylcaprolactame-based (co)polymers (PNVC), and discuss the different routes of polymer synthesis, copolymer properties, and formation of particulate structures, surface grafts, and hydrogels, as well as potential applications. PNVCs have an LCST and therefore show thermosensitive behavior. In contrast to poly(N-isopropylacrylamide)s, the thermal transitions of PNVCs are tailorable more efficiently, so that in fact not only proof of concept studies, but actual biomedical applications can be envisioned. Shi et al. report on thermosensitive polymeric micelles. By employing π−π stacking interactions of parts of the micelle forming block-copolymers, photosensitizers can be efficiently loaded also exploiting the interaction with the aromatic groups. In this way, aggregation and/or premature release of the load can be prevented. At the same time, singlet oxygen production by irradiation is more biologically effective than in micelles not containing aromatic groups. Bridging chemical structure and biological effects is essential for the design of antimicrobial polymers. Jain et al. reviewed the literature on this topic. By explaining the different modes of action, structure-activity relations, as well as fields of application, are discussed. In this way, a valuable basis for researchers in the field is provided. The geometry of three-dimensional microwell structures influences the morphology, migration, and proliferation of human adipose-derived mesenchymal stem cells. Xu et al. could gain a deeper biological understanding by systematically investigating a series of microprocessed medical grade polymers, highlighting the importance of the collaboration between chemists and biologists. Interestingly, the cell behavior such as differentiation and migration could be related to changes in the gene expression profile, especially connected to the intracellular Rho/ROCK pathway. These fundamental studies may allow a transfer to structured implant materials in an in vivo situation. Finally, Fontana et al. present the guiding of stem cell differentiation towards nucleus pulposos (NP)-like phenotypes important for regeneration of intervertebral discs by tailoring the cell's microenvironment in microgels. The microgels were based on type II collagen and hyaluronan. By changing the amount of collagen in the microgels, the resistance to enzymatic degradation, but also the efficiency of promoting NP-like differentiation of the stem cells could be tailored. The three complementing approaches, use of physical and chemical cues in biomaterial design as well as understanding the biological effects of cell-material interactions presented in the articles of this SI exemplarily show the necessary interdisciplinarity of biomaterial research and illustrate the potential of multifunctional polymers in biomedical applications. The guest editors thank Dr. Lorna Stimson and Wiley-VCH for the realization of this special issue, and Sabine Benner for editorial and administrative support. Prof. Andreas Lendlein, Institute of Biomaterial, Science Helmholtz-Zentrum, Geesthacht and University of Potsdam, Germany Dr. Axel T. Neffe Institute of Biomaterial Science, Helmholtz-Zentrum Geesthacht and University of Potsdam, Germany Prof. Christine Jérôme Center for Education and Research on Macromolecules (CERM), University of Liège Belgium