Volume 14, Issue 3-4 - Special Issue: Milestones in Biomaterials Research / on the Occasion of the 20th Anniversary of the German Society for Biomaterials

Prosthetic devices have existed for centuries. Originally prosthetics were simply replacements for missing limbs, but now they help people have extremely active lives. Such improvements have been made possible because of new surgical techniques, advancement of components for making prosthetics, and creative engineering ideas. In this article we will attempt to provide an insight to the history of prosthetics and some of the surgical techniques employed, albeit very basic. Mythological tales prove that some revered gods and goddesses of ancient cultures could have a handicap. We then develop the disabling causes in old civilisations going from legs and foot prostheses to arm and hand prostheses. For these limb replacements, we give examples of famous amputees. We then consider the head as a favorite place for implants and prostheses and develop trepanation with skull implants, eye and nose prostheses to finally treat the large domain of dental restorations.

Osteoporosis and osteoporotic fractures have a high impact on the quality of life of patients and on the financial aspects of Western health care systems. There is a tremendous need for improvement of the treatment outcome in osteoporotic fracture patients and biomaterials are of interest to stimulate fracture healing in those patients. For adequate characterization of biomaterials for the indication of osteoporotic fractures a clinically relevant animal model with a fracture defect in the metaphyseal region of a long bone in an osteoporotic animal is required. We recently developed a 3–5 mm wedge shaped osteotomy model in the distal metaphysis of the femur in osteoporotic rats. There are different biomaterials approaches to stimulate fracture healing in osteoporotic fractures and recently published results suggest that the composite implants from osteoconductive carriers combined with osteoanabolic agents, e.g., strontium-modified calcium phosphate cement, can enhance new bone formation. Further in vivo and clinical research will be necessary in the future for introduction of new and different types of biomaterials for osteoporotic fracture patients into all day clinical practice.

Bone tissue engineering includes a broad range of strategies and approaches to improve osteoinductive and osteoconductive properties of biomaterials. One approach is applying components of the native extracellular matrix (ECM) to mimic a favorable environment for bone forming cells like osteoblasts and their progenitors. The development of such artificial extracellular matrices (aECMs) is based on collagen, which can be modified by glycoproteins, proteoglycans and glycosaminoglycans. This article reviews the preparation, immobilization and the biochemical characteristics of these coatings for scaffolds and implants. In addition, the influence of aECM coating on cells, bone-implant contact and new bone formation in small and large animals is discussed.

The interaction of cells with material surfaces is of fundamental relevance and contributes to the clinical success of implants. Cells sense their physico-chemical environment resulting in focal adhesion reorganization, spatio-temporal localization and activation of integrin dependent signalling proteins as well as phenotypic changes, e.g., of the actin cytoskeleton. The technology of designing instructive biomaterials involves chemical modifications by grafting of chemical groups, adhesion ligands and growth factors. Physical modifications of the materials are created by structuring the surfaces stochastically and geometrically and by modifications of the material stiffness. Insights into the mechanism at the interface that are involved in the regulation of cells such as stem cells, osteoblasts and chondrocytes by materials will advance the development of innovative biomaterials in regenerative medicine.

Nanoparticles are used in medicine to deliver drugs, for imaging, for vaccination and for local heating of tissue (tumor thermotherapy). If malignant tissue shall be addressed, it is of prime importance to direct the nanoparticles to their target. This can be accomplished by making use of physical effects (e.g., the EPR effect: enhanced permeation and retention) or by chemical modification of the nanoparticles to specifically recognize cells or tissues. The efficiency of the targeting can be assessed by in vitro cell culture experiments and also in vivo in animal experiments. As they are closest to the practical clinical application, in vivo imaging methods are particularly suitable to monitor the targeting. In general, a limited colloid-chemical stability of the nanoparticles in a biological environment and the formation of a protein corona around the nanoparticle may constrain their targeting ability. The current state of such targeting strategies is reviewed and discussed.

Scaffold-based tissue engineering approaches have been under investigation for more than 30 years now and many different techniques have been developed in order to engineer various tissues of the body. Some of them have been translated from bench to bedside, yet many are still under intensive examination. Biodegradable scaffolds applied in tissue engineering aim to temporarily substitute for the extracellular matrix and its complex biological functions during the regeneration and/or remodelling period, and are subsequently degraded and replaced by new tissue. We herein discuss how knowledge from developmental biology and collective tissue healing biology can be applied to optimise the design of scaffolds that promote fundamental steps in tissue regeneration by creating a suitable microenvironment. The review focuses on the design and fabrication of scaffolds for bone tissue engineering, yet also highlights general considerations which apply to scaffolds used in any tissue engineering strategy. We then turn to scaffold manufacturing where a plethora of design and fabrication technologies have been applied to process biomaterials into scaffolds for bone tissue engineering and other applications. Each manufacturing technology has its advantages and disadvantages from a processing, material science and biological point of view. We herein review several additive manufacturing technologies, which in the authors’ opinion currently are most relevant for scaffold-based bone tissue engineering. We also provide a future outlook on Image-guided Tissue Engineering, Additive Tissue Manufacturing and Guided Tissue Regeneration with respect to tissue engineering in general and bone tissue engineering in particular.

In biological media, nanoparticles acquire a coating of biomolecules (proteins, lipids, polysaccharides) from their surroundings, which reduces their surface energy and confers a biological identity to the particles. This adsorbed layer is the interface between the nanomaterial and living systems and therefore plays a significant role in determining the fate and behaviour of the nanoparticles. This review summarises the state of the art in terms of understanding the bio-nano interface and provides direction for potential future research and recommendations for future priorities and strategies to support the safe implementation of nanotechnologies. The central premise is that nanomaterials must be studied as biological entities under the appropriate exposure conditions and that this should be implemented in study design and reporting for nanosafety assessment. The implications of the bio-nano interface for nanomaterials fate and behaviour are described in light of four interlinked perspectives: the Coating concept; the Translocation concept; the Signalling concept, and the Kinetics concept. A key conclusion is that nanoparticles cannot be viewed as non-interacting species, but rather must be thought of, and studied as, biological entities, where their interaction with the environment is mediated by the proteins and other biomolecules that adsorb to them, and the key parameter to characterise then becomes the nature, composition and evolution of the bio-nano interface.

Medical devices made of polymers are often protected against infection-relevant biofilm formation by embedding nanoparticles as a source of bioactive metal ion release. Safe application of such nanocomposites requires finding the optimal ion dose and identifying the cross-effects caused by material mixtures. This study investigated the safety and antimicrobial efficacy of thermoplastic polyurethane (TPU), which is widely used for medical devices, e.g., catheters containing zinc, silver, copper and magnesium nanoparticles, respectively, and combinations thereof. Nanoparticles were generated by using pulsed laser ablation in polymer solution. We found that the composites embedded with nanosilver were noncytotoxic to cells but toxic to bacteria, with an optimal effect at 0.5 wt%. In contrast, zinc, copper, and magnesium nanoparticle composites did not inhibit bacteria growth. Interestingly, by combining the antibacterial metals (Ag, Cu) with nanoparticles made of elements required in biological systems (Zn, Mg), we observed an altered ion release and corresponding changes to their antibacterial efficacy and biocompatibility. The combination of silver with magnesium in the nanocomposites did increase both the amount and rate of silver ion release, and resulted in an increased antimicrobial effect of this Ag-Mg-TPU composite material. The therapeutic window of silver could not be changed quantitatively by the Ag-Mg combination, but less wt% silver was required for achieving antimicrobial efficacy because of faster ion release in the clinically relevant, critical initial phase of immersion. According to our observations, the mechanism of Mg increasing the mass-specific bio-effectivity of silver is possibly nonelectrochemical but volumetric. A fine-tuning of the Mg to Ag ratio and the overall load would be required to test whether a larger therapeutic window compared with Ag composites can be gained by the mixed Mg-Ag nanocomposites. Overall, the addition of Mg to Ag reduces the lag phase of bioactivity by increasing the Ag ion release in the critical first days after application of the medical device.

Environment hazards and risks of engineered NanoParticles (NPs) have been debated in recent years. In this paper, the effects of silver (Ag) and carbon (C) NPs were explored in sea urchin Paracentrotus lividus ( P. lividus ) development. Fertilization and development of P. lividus up to the pluteus stage were assayed in the presence of increasing amounts of NPs. The embryotoxicity test performed on sea urchin P. lividus , from fertilization until the larva stage, revealed that both AgNPs and CNPs were embryotoxic since they caused embryo malformations and alteration of the normal progression through the development stages. Embryonic development was slowed down by AgNPs and sped up by CNPs. Interestingly, AgNPs-induced malformations led embryos to die in a concentration-dependent manner; while embryos bearing CNPs-induced malformations survived for a longer time.

Currently it is not fully understood how carbon nanotubes (CNTs) may affect human health. Despite this, CNTs are produced at a tonne mass scale yearly. Due to their large production and intended use within a variety of applications it is imperative that a clear understanding of the hazard potential of CNTs is gained. The aim of this study therefore was to assess the impact of five different industrially produced CNTs which varied in their physical properties on the viability of human monocyte derived macrophages (MDM), and subsequently, at sub-lethal concentrations (0.005–0.02 mg/mL), their ability to cause oxidative stress and a pro-inflammatory response in these important immune cells over a 24-h period. None of the CNTs caused significant cytotoxicity up to 0.02 mg/mL after 24 h. Only the long multi-walled CNTs (MWNCTs) caused a significant, dose-dependent (0.005–0.02 mg/mL) reactive oxygen species production, whilst bundled MWCNTs showed a significant tumor necrosis factor alpha release after 24 h exposure at 0.02 mg/mL. No effects were observed for either tangled MWCNTs or short MWCNTs. It can be concluded from the findings of the present study that the industrially produced CNTs studied can cause hazardous effects in vitro that may be associated with their physical properties.