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 non-covalent 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 will briefly recount the state of supramolecular biomaterials in the Dutch academic and industrial research and development context. This review will provide 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.

The Official Journal of EuroPCR and the European Association of Percutaneous Cardiovascular Interventions (EAPCI)

Vascular in situ tissue engineering encompasses a single-step approach with a wide adaptive potential and true off-the-shelf availability for vascular grafts. However, a synchronized balance between breakdown of the scaffold material and neo-tissue formation is essential. Chronic kidney disease (CKD) may influence this balance, lowering the usability of these grafts for vascular access in end-stage CKD patients on dialysis. We aimed to investigate the effects of CKD on in vivo scaffold breakdown and tissue formation in grafts made of electrospun, modular, supramolecular polycarbonate with ureido-pyrimidinone moieties (PC-UPy). We implanted PC-UPy aortic interposition grafts (n = 40) in a rat 5/6th nephrectomy model that mimics systemic conditions in human CKD patients. We studied patency, mechanical stability, extracellular matrix (ECM) components, total cellularity, vascular tissue formation, and vascular calcification in CKD and healthy rats at 2, 4, 8, and 12 weeks post-implantation. Our study shows successful in vivo application of a slow-degrading small-diameter vascular graft that supports adequate in situ vascular tissue formation. Despite systemic inflammation associated with CKD, no influence of CKD on patency (Sham: 95% vs CKD: 100%), mechanical stability, ECM formation (Sirius red+, Sham 16.5% vs CKD 25.0%–p:0.83), tissue composition, and immune cell infiltration was found. We did find a limited increase in vascular calcification at 12 weeks (Sham 0.08% vs CKD 0.80%—p:0.02) in grafts implanted in CKD animals. However, this was not associated with increased stiffness in the explants. Our findings suggest that disease-specific graft design may not be necessary for use in CKD patients on dialysis.

Synthetic vascular grafts continue to face significant challenges in small-diameter clinical applications, particularly for dialysis access. Endogenous tissue restoration (ETR) is emerging as a promising solution, harnessing the body’s natural healing mechanisms to restore functional tissue. Recent advances in biomaterials – especially supramolecular polymers – have enabled the development of biocompatible, biodegradable, and tunable scaffolds that can be precisely engineered for clinical use. Unlike conventional grafts that often rely on persistent polyfluoroalkyl substances (PFAS)-based chemistries, the aXess restorative dialysis access graft utilizes supramolecular polymer technology to avoid “forever chemicals” and support ETR. This chapter provides an overview of the preclinical and clinical application of supramolecular polymers for ETR, with a focus on vascular access, and demonstrates the potential of supramolecular technology to address both clinical and environmental challenges in bringing ETR to patients.