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Synthetically designed biomaterials strive to recapitulate and mimic the complex environment of natural systems. Using natural materials as a guide, the ability to create high-performance biomaterials that control cell fate, and support the next generation of cell- and tissue-based therapeutics, is starting to emerge. Supramolecular chemistry takes inspiration from the wealth of noncovalent interactions found in natural materials that are inherently complex, and using the skills of synthetic and polymer chemistry, recreates simple systems to imitate their features. Within the past decade, supramolecular biomaterials have shown utility in tissue engineering and the progress predicts a bright future. On this 30th anniversary of the Netherlands Biomaterials and Tissue Engineering society, we briefly recount the state of supramolecular biomaterials in the Dutch academic and industrial research and development context. This review provides the background, recent advances, industrial successes and challenges, as well as future directions of the field, as we see it. Throughout this work, we notice the intricate interplay between simplicity and complexity in creating more advanced solutions. We hope that the interplay and juxtaposition between these two forces can propel the field forward. Impact statement Supramolecular biomaterials based on noncovalent interactions hold the ability to rebuild some of the complexity of natural biomaterials in synthetic systems. While still in its infancy, the field is currently vigorously moving from fundamental experiments toward applications and products in the tissue engineering and regenerative medicine arena. Herein, we review the current state of the field in the Netherlands. While supramolecular biomaterials have incredible potential, systematic studies, balancing complexity and simplicity, efficient translation, and enhanced performance are all required for success of these strategies. As we move the field toward commercial solutions for clinical patients, we must also pay homage and remember the fundamental studies that allow these jumps in innovation.

Meniscus regeneration could be enhanced by targeting meniscus cells and mesenchymal stromal cells (MSCs) with the right growth factors. Combining these growth factors with the Collagen Meniscus Implant (CMI®) could accelerate cell ingrowth and tissue formation in the implant and thereby improve clinical outcomes. Using a transwell migration assay and a micro‐wound assay, the effect of insulin‐like growth factor‐1, platelet‐derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor beta 1 (TGF‐β1), fibroblast growth factor, and platelet lysate (PL) on migration and proliferation of meniscus cells and MSCs was assessed. The formation of extracellular matrix under influence of the above‐mentioned growth factors was assessed after 28 days of culture of both MSCs and meniscus cells. As a proof of concept, the CMI® was functionalized with a VEGF binding peptide and coated with platelet‐rich plasma (PRP) for clinical application. Our results demonstrate that PDGF, TGF‐β1, and PL stimulate migration, proliferation, and/or extracellular matrix production of meniscus cells and MSCs. Additionally, the CMI® was successfully functionalized with a VEGF binding peptide and PRP which increased migration of meniscus cell and MSC into the implant. This study demonstrates proof of concept of functionalizing the CMI® with growth factor binding peptides. A CMI® functionalized with the right growth factors holds great potential for meniscus replacement after partial meniscectomy.

Endothelial cells play a central role in the vascular system, where their function is tightly regulated by both cell-extracellular matrix (e.g., via integrins) and cell-cell interactions (e.g., via cadherins). In this study, we incorporated cholesterol-modified integrin and N-cadherin peptide binding ligands in fluid supported lipid bilayers. Human umbilical vein endothelial cell adhesion, spreading and vinculin localization in these cells were dependent on ligand density. One composition led to observe a higher extent of cell spreading, where cells exhibited extensive lamellipodia formation and a qualitatively more distinct N-cadherin localization at the cell periphery, which is indicative of N-cadherin clustering and a mimic of cell-cell contact formation. The results can be used to reconstitute the endothelial-pericyte interface on biomedical devices and materials.

Biomaterial integration into bone requires optimal surface conditions to promote osteoprogenitor behavior, which is affected by integrin-binding via arginine-glycine-aspartate (RGD). RGD-functionalized supported lipid bilayers (SLBs) might be interesting as biomaterial coating in bone regeneration, because they allow integration of proteins, for example, growth factors, cytokines, and/or antibacterial agents. Since it is unknown whether and how they affect osteoprogenitor adhesion and differentiation, the aim was to investigate adhesion, focal adhesion formation, morphology, proliferation, and osteogenic potential of pre-osteoblasts cultured on RGD-functionalized SLBs compared to unfunctionalized SLBs and poly-l-lysine (PLL). After 17 hr, pre-osteoblast density on SLBs without or with RGD was similar, but lower than on PLL. Cell surface area, elongation, and number and size of phospho-paxillin clusters were also similar. Cells on SLBs without or with RGD were smaller, more elongated, and had less and smaller phospho-paxillin clusters than on PLL. OPN expression was increased on SLBs with RGD compared to PLL. Moreover, after 1 week, COL1a1 expression was increased on SLBs without or with RGD. In conclusion, pre-osteoblast adhesion and enhanced differentiation were realized for the first time on RGD-functionalized SLBs, pointing to a new horizon in the management of bone regeneration using biomaterials. Together with SLBs nonfouling nature and the possibility of adjusting SLB fluidity and peptide content make SLBs highly promising as substrate to develop innovative biomimetic coatings for biomaterials in bone regeneration.

With the rising number of Unmanned Aerial Systems (UAS) flying in the sky, an increase in collisions with manned aircraft seems inevitable. Since these devices are permitted to operate in airspace which they share with rotorcraft, a helicopter is certainly not retained from the risk of colliding with a UAS. The only prevailing impact related certification requirement for rotorcraft is the §29.631, which is only applicable to all larger (Part 29) rotorcraft. This requirement states that the rotorcraft must be capable of safe continuation of the flight and/or safe landing after an impact with a 1 kg bird up to the rotorcraft’s maximum horizontal velocity. In this paper, simulations have been performed in explicit Finite Element software to assess how much damage a Part 29 compliant helicopter would sustain after colliding with a UAS. For this purpose, an Agusta A-109 helicopter windshield was impacted by a DJI Phantom III quadcopter UAS under various conditions. The results of the simulations showed that the windshield would sustain severe damage after the impact. Not only would the windshield break into dangerous fragments that could enter the cockpit, parts of the UAS would also penetrate the windshield. These items could strike the crew and a safe continuation of the flight and/or safe landing following the impact cannot be guaranteed. A similar level of safety compared to the bird strike requirement in the prevailing certification requirement is therefore not assured.

Quantification of the multivalent interactions of influenza viruses binding at interfaces may provide ways to tackle key biological questions regarding influenza virulence and zoonoses. Yet, the deconvolution of the contributions of molecular and interfacial parameters, such as valency, interaction area, and receptor density, to the binding of whole viruses is hindered by difficulties in the direct determination of these parameters. We report here a chemical platform technology to study the binding of multivalent recombinant hemagglutinin (rHA) nanoparticles at artificial sialoglycan cell receptor-presenting interfaces in which all these parameters can be derived, thus allowing the desired full and quantitative binding analysis. SiO 2 substrates were functionalized with supported lipid bilayers containing a targeted and tunable fraction of a biotinylated lipid, followed by the adsorption of streptavidin and biotinylated polyvalent 2,3-or 2,6-sialyl lactosamine (SLN). rHA nanoparticles were used as a virus mimic to provide a good prediction of the number of interactions involved in binding. Low nanomolar affinities and selectivities for binding at the 2,6-SLN platforms were observed for rHA particles from three different virus variants. When fitting the data to a multivalency model, the nanomolar overall affinity appears to be achieved by 6-9 HA-sugar molecular interaction pairs, which individually present a rapid association/dissociation behavior. This dynamic behavior may be an essential biological attribute in the functioning of the influenza virus.

Three-dimensional (3D) scaffolds with chemical diversity are significant to direct cell adhesion onto targeted surfaces, which provides solutions to further control over cell fates and even tissue formation. However, the site-specific modification of specific biomolecules to realize selective cell adhesion has been a challenge with the current methods when building 3D scaffolds. Conventional methods of immersing as-prepared structures in solutions of biomolecules lead to nonselective adsorption; recent printing methods have to address the problem of switching multiple nozzles containing different biomolecules. The recently developed concept of macroscopic supramolecular assembly (MSA) based on the idea of “modular assembly” is promising to fabricate such 3D scaffolds with advantages of flexible design and combination of diverse modules with different surface chemistry. Herein we report an MSA method to fabricate 3D ordered structures with internal chemical diversity for site-selective cell adhesion. The 3D structure is prepared via 3D alignment of polydimethylsiloxane (PDMS) building blocks with magnetic pick-and-place operation and subsequent interfacial bindings between PDMS based on host/guest molecular recognition. The site-specific cell affinity is realized by distributing targeted building blocks that are modified with polylysine molecules of opposite chiralities: PDMS modified with films containing poly-l-lysine (PLL) show higher cell density than those with poly-d-lysine (PDL). This principle of selective cell adhesion directed simply by spatial distribution of chiral molecules has been proven effective for five different cell lines. This facile MSA strategy holds promise to build complex 3D microenvironment with on-demand chemical/biological diversities, which is meaningful to study cell/material interactions and even tissue formation.

Simple Summary For the enrichment of very rare cells, such as Circulating Tumor Cells (CTCs), immunomagnetic enrichment is frequently used. For this purpose, magnetic nanoparticles (MNPs) coated with specific antibodies directed against cancer cells are used. In this review, we look at the properties such a particle needs to have in order to be used successfully, and describe the different methods used in the production of such a particle as well as the methods for their separation. Additionally, an overview is given of the antibodies that could potentially be used for this purpose. Abstract Here, we review the characteristics and synthesis of magnetic nanoparticles (MNPs) and place these in the context of their usage in the immunomagnetic enrichment of Circulating Tumor Cells (CTCs). The importance of the different characteristics is explained, the need for a very specific enrichment is emphasized and different (commercial) magnetic separation techniques are shown. As the specificity of an MNP is in a large part dependent on the antibody coated onto the particle, different strategies in the coupling of specific antibodies as well as an overview of the available antibodies is given.