Self-folding metabiomaterials

An important goal of bone tissue engineering is the development of synthetic bio-scaffolds that would eliminate the need for bone transplantation, also known as bone grafting. Bone grafting is associated with some serious limitations such, as morbidity at the donor-site and shortage of donor tissue. Therefore, scientist have been trying to develop synthetic bone substituting materials that serve as a platform for the regeneration of tissue. Despite all the effort made towards that goal, no perfect alternative has been developed yet. The formulated requirements for the fabrication of bone scaffolds raise a serious challenge towards the development of such synthetic biomaterials. In order to mimic the structure of living bony tissue, scaffolds need to be composed of a large number of small, interconnected unit-cells, thereby providing a large surface area for cell attachment and tissue ingrowth. In addition, the mechanical properties of the scaffold should match those of the native bone tissue. A too high stiffness could lead to stress shielding and associated implant loosing while a weak scaffold offers a limited load-bearing capacity. Finally, synthetic biomaterials need to be biocompatible. This thesis presents a number of strategies for the development of synthetic bone scaffolds using shape-shifting techniques. As compared with alternative approaches, such as additive manufacturing, self-folding materials allow for the employment of planar fabrication techniques to embed the initially flat material with a variety of surface-related functionalities. Examples of such surface-features are bactericidal or osteogenic nano-patterns. Upon activation, the initially flat construct folds to create complex 3D constructs with embedded surface-features, which are highly beneficial in the context of porous biomaterials. The first two chapters of this thesis are related to fundamental aspects of shape-shifting materials. More specifically, in Chapter 2, we reviewed the different mechanisms for the programming of shape-shifting within flat materials. In addition, we describe the development of analytical and computational models to study the theoretical stiffness limits of self-folding hinges (Chapter 3). We found a maximum effective stiffness of 1.5 GPa for shape-memory polymers self-folding elements. In the second part of this thesis, we present the development of three different shape-shifting techniques. The first technique is based on the 4D printing of shape-memory polymer materials. During the extrusion of the filaments, the polymers chains align along the printing direction. This deformation is then stored as memory inside the structure of the material. Heating the as-printed construct allows for the relaxation of the programmed stress. Based on the alignment of the extruded filaments, different shape-shifting behaviors can be programmed. Both the fabrication of 2D-to-3D shape-shifting materials (Chapter 4) as well the production of deployable materials and devices (i.e., 3D-to-3D shape shifting) (Chapter 5) was studied. In Chapter 6, we focus on the development of a purely mechanical shape-shifting method. By incorporating different kirigami patterns within the material, large amounts of elastic and permanent deformations can be programmed upon stretching the material. Subsequent release of the pre-stretch allows for the recovery of the elastic deformations, driving the shape-shifting of the material. The main advantage of such a mechanical approach is that it could be applied to many different materials. The third shape-shifting technique is inspired by sheet metal forming processes (Chapter 7). Miniaturized automated folding devices were developed for the folding of cubic lattice structures. As a demonstration, metamaterials comprising 125 cubic unit-cells with a unit-cell dimension of 2.0 mm were fabricated. In contrast to conventional self-folding methods, sharp folds can be realized in metal sheets using the presented approach. Therefore, metamaterials with a high stiffness can be folded. In addition, a variety of surface-patterns can be incorporated into the initially flat sheets. Protected by a thin layer of coating, the applied surface-related functionalities remain undamaged during the folding process. Finally, a series of cell culture experiments were performed to demonstrate the ability of the folded functionalized materials to serve as a tissue engineering scaffold. In general, the presented shape-shifting techniques are of relevance to a variety of applications, such as optical metamaterials and 3D electronics. However, the specific aim of this thesis is the development of self-folding materials that can be applied as tissue engineering scaffolds. Considering the listed requirements, the folding technique inspired by sheet metal forming meet the necessary requirements the best. However, additional research towards further miniaturization of the scaffolds resulting from different methods as well as an increase in their stiffness are required for application in clinical settings. In the case of the automatically folded scaffolds, the initial cell culture experiments showed promising results and the proposed folding method can, indeed, serve as a platform for further biological testing