Macromolecular Biomaterials Interfacing with Cells

Several months ago, the Editor of Macromolecular Bioscience - Dr. Mara Staffilani - asked me to propose a theme for a special issue generally devoted to some medical applications of macromolecules. Although very large, I personally found this theme fascinating. We, therefore, decided to focus on macromolecular biomaterials that interface with cells. In fact, in my humble opinion, this topic truly highlights one of the main issues that still remain partially unsolved in the biomaterials field: The development of pro-active materials. After four to five decades of research in the field, this is what has emerged: Biomaterials should be pro-active. This means that when biomaterials are implanted, the surrounding cells and tissues (of the patients) should ‘interact with’ instead of ‘react to’ the implant. It now seems simple, even evident, but going back to the literature of the 1960s, it is not uncommon to read that inertness was the main requirement the first generation of biomaterials had to fulfill. Today, it is well known that reactions tend to generate mainly negative effects, while interactions are expected to generate positive effects, which directs us towards the success of the implant, its functionality, the health of the patient and their quality of life. What we still lack is how to be successful in allowing materials to communicate with cells. We know that cells are able to communicate with each other towards several pathways, and that materials are inert, while cells are living. This still represents a tight scientific bottleneck not easy to overcome. The great advances made in biology in the last decades have opened new horizons for biomaterial scientists. Firstly, this newly developed knowledge pushed researchers to closely mimic biological structures and mechanisms. Secondly, this inspired researchers worldwide to develop different but complementary approaches to targeting specific interactions between materials and cells. Factual examples of this are i) the special issue (2/2007) of Macromolecular Bioscience devoted to new distinct classes of bio-inspired materials, and ii) this special issue (that you are handling and reading), which is devoted to macromolecular biomaterials that interface with cells. Tissue engineering and regenerative medicine constitute two other clear examples of the results generated by merging biology and engineering. However, one should not forget that the surgical replacement of diseased tissues and dysfunctional organs with biomaterials and artificial organs (which are expected to remain functional for the rest of the life of the patient) still clinically represent the alternative of choice. Biomaterials and artificial organs today allow restoration, on a short to medium term, of the quality of life for millions and millions of patients annually worldwide. In this context, although promising and already with a few external applications, tissue engineering and regenerative medicine are on target to allow patients to be clinically treated in only one to two decades from now (at least). However, the main advantage is that tissue engineering and regenerative medicine are expected to restore the quality of life of patients for the long term. Although no one can exactly predict when and how, it is logic to expect that in the coming years, the number of tissue-engineered products clinically available for surgery, for example, will certainly increase. In some decades, it is reasonable to expect the development of a proven ability to regenerate organized tissues or functional organs in vitro and even in vivo from human healthy cells to replace or restore diseased tissues or pathological (non functional) organs. In this context, the ability to develop materials able to interface with cells remains one of the main challenges. Macromolecules are particularly well suited for interfacing with cells, mainly because the biological environment, to which cells are used to interacting, is particularly rich in macromolecular components. Macromolecular biomaterials interfacing with cells cannot be reduced to a mere question of technology. It concerns a number of sciences and engineering specialities, biology and its facets, and clinical sciences as well. For most of these aspects, in this issue we are able to include specific contributions of selected scientists with renowned expertise. As a matter of fact, one of the main objectives of this issue was to highlight the mutual benefits in promoting a multidisciplinary approach based on multi-competencies, instead of emphasizing on monocompetence. In my humble point of view, this constitutes the major frontier that people involved in this scientific field need to overcome prior to the generation of true knowledge, significant breakthroughs, and before real advances will be able to have considerable effect in improving the patients' quality of life worldwide. I shall dream that, based on the highest ethical and scientific matter, researchers will not favor to invest all the available resources in well recognized topics, but that from time to time they will dare to explore adventurous and unconventional paths that are perhaps even out-of-fashion but promising. Therefore, I am convinced that research on topics that involve multiple disciplines could strongly benefit from the synergy of a multi-competencies approach instead of the traditional way, which usually restrains a scientific project to a specific competence, mainly with respect to financial matters. It is up to researchers to choose the relatively new open path of multi-competence collaborations. Research approaches based on multi-competencies have also an increased potential to creatively solve new complex problems. In a recent book (Five minds for the future) a very senior scientist (Professor Howard Gardner), described creating minds as those having the capacity to uncover and clarify new problems. It seems that most of the teaching processes in schools and universities lead to the development of a “converging intelligence”, which is the one not easily influenced by imagination. It also seems that the development of the “diverging intelligence”, the one more linked to creativity, the capacity of multiple and original solutions, is rarely stimulated by academic and scholar programs. These latter, are organized and implemented in order to stimulate minds to appropriately answer to a given question or to solve a problem with a given solution (converging intelligence). As a result, creative thinking is unequivocally discouraged, although it is the only one required for ensuring the progress of knowledge and the advancement of science. Imagination is more important than knowledge, wrote Albert Einstein. In this context, mastering the complexity of multidisciplinary challenges, like those that have to be overpasses in tissue engineering, necessarily require creativity. By promoting different analytical processes leading to solve a targeted problem, the approaches by multicompetencies certainly provide a valid creative environment. In this context, the objective of this special issue is to enable the reader to better understand the extent of this fascinating field. It is our hope that in this issue senior scientists will find interdisciplinary ideas on how to solve specific problems or to overcome technical bottlenecks, while young scientists will be able to rapidly but comprehensively develop a clear and unbiased portrait of this field and of the dimension of its activity. This special issue presents twenty papers that report data, ideas, strategies, and results over the following six topics: The first manuscript of this review is a truly inspiring work with a visionary approach. It concisely reviews and nicely presents creative results for the design and fabrication of synthetic self-assembling peptide scaffolds for regenerative medicine and tissue engineering. Two works aimed at the prediction of cell–material interactions by a computational approach are then included. Although approximated, computational approaches are absolutely helpful to understand how cells interface materials, and (in my opinion) they should be mandatory and carried out in parallel or prior to most experimental works. Three-dimensional cultures for tissue engineering require appropriate environments, specific methods for assessing cell phenotypes, and quantitative techniques to investigate cell activity. The first work of this section reports the original characterization of the oscillatory flow perfusion seeding of rat mesenchimal stem cells on arg-gly-asp (RGD)-modified poly(L-lactic acid) foams. The second work describes how atomic force microscopy/force modulation microscopy techniques could be used to extract mechanical information on mesenchimal stem cells submitted to osteogenic, chondrogenic, and adipogenic mesoderm phenotypes. The third work proposes a comparative test to investigate endothelial cell adhesion onto proteins by an original electrochemical method. An elegant approach to allow materials ‘to communicate’ with cells and, therefore, to stimulate the materials' pro-activeness, is one in which they are loaded with a gene or drug in such a manner to target their release. The first work of this section describes how degradable macromolecular biomaterials can be structured to form complexes with DNA and to show suitable physicochemical properties for gene-delivery systems. The second paper investigates how small amounts of poly(ethylene glycol) segments can be incorporated into two-component polyanhydrides to speed up the erosion rate as a result of increased hydrophilicity and decreased crystallinity of the degradation products. Finally, the third work focuses on the preparation of biodegradable microspheres with tailored properties for potential applications in the medical field as temporary drug and cell carriers. Designing the next generation of implantable macromolecular biomaterials for the replacement or regeneration of bone also needs a multi-competence approach. The first work presents an overview of polymeric materials used in orthopaedic tissue engineering applications, which is followed by a detailed discussion on bone morphogenetic proteins and how synthetic nano-polymers can be used as carriers. In the second work, the combined potential of i) improving fluid flow, ii) enlarging the scaffold pore sizes, and iii) targeting the process of scaffold fabrication is investigated for the culture of human mesenchimal stem cells. Finally, the third paper highlights the technology based on macromolecular-bone protein linkers. Materials to support specific cells during metabolic activities, which are essential for human life, are required to show synergistically high biological performances and high chemical and mechanical resistances. This represents a major challenge from a biomaterial point of view. The first two works explore the properties of macromolecular membranes for bioartificial liver and/or hepatocyte culture systems. The third work focuses on the design of constructs to function in the complex mechanical environment of the bladder wall. The potential considerations for such demanding applications of macromolecular materials with nanometric surface features (less than 100 nm) as bio-absorptive substrates is carefully investigated. The regeneration of vessels requires cylindrical three-dimensional structures that can be progressively seeded and cultured with cells in a layer-by-layer approach. This is expected to lead to concentric functional tissues organized by layers. The first work of this section is a comprehensive review of macromolecular biomaterials used, or that have the possibility to be used, in vascular tissue engineering. The development of scaffolds in which macromolecules and cells are placed to work together directly in a cylindrical configuration is then presented. The third work presents a new method to synthesize hydrogels and report their characterization and biological properties. The last two works are devoted to surface modifications of macromolecular surfaces to improve the clinical performances of i) vascular prostheses, and ii) vascular stent-grafts, currently commercially available in hospitals. Finally, I would like to thank all the people who, directly or indirectly, have made this special issue possible, first of all, the authors themselves who enthusiastically answered my invitation. Special thanks also go to Mara Staffilani and all the editorial staff at Wiley-VCH in Germany, without their efficacy and efficiency this special issue would never have been created. Finally, I would like to thank all you readers, to whom I personally wish that the time you invest in reading this special issue is both stimulating and enriching.

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