Advancing Frontiers in Bone Bioprinting

Detailed descriptions of the structural features of bone abound in the literature; however, the mechanical properties of bone, in particular those at the micro- and nano-structural level, remain poorly understood. This paper surveys the mechanical data that are available, with an emphasis on the relationship between the complex hierarchical structure of bone and its mechanical properties. Attempts to predict the mechanical properties of bone by applying composite rule of mixtures formulae have been only moderately successful, making it clear that an accurate model should include the molecular interactions or physical mechanisms involved in transfer of load across the bone material subunits. Models of this sort cannot be constructed before more information is available about the interactions between the various organic and inorganic components. Therefore, further investigations of mechanical properties at the 'materials level', in addition to the studies at the 'structural level' are needed to fill the gap in our present knowledge and to achieve a complete understanding of the mechanical properties of bone.

We present a new 4D printing approach that can create high resolution (up to a few microns), multimaterial shape memory polymer (SMP) architectures. The approach is based on high resolution projection microstereolithography (PμSL) and uses a family of photo-curable methacrylate based copolymer networks. We designed the constituents and compositions to exhibit desired thermomechanical behavior (including rubbery modulus, glass transition temperature and failure strain which is more than 300% and larger than any existing printable materials) to enable controlled shape memory behavior. We used a high resolution, high contrast digital micro display to ensure high resolution of photo-curing methacrylate based SMPs that requires higher exposure energy than more common acrylate based polymers. An automated material exchange process enables the manufacture of 3D composite architectures from multiple photo-curable SMPs. In order to understand the behavior of the 3D composite microarchitectures, we carry out high fidelity computational simulations of their complex nonlinear, time-dependent behavior and study important design considerations including local deformation, shape fixity and free recovery rate. Simulations are in good agreement with experiments for a series of single and multimaterial components and can be used to facilitate the design of SMP 3D structures.

The present paper intends to overview a wide range of natural-origin polymers with special focus on proteins and polysaccharides (the systems more inspired on the extracellular matrix) that are being used in research, or might be potentially useful as carriers systems for active biomolecules or as cell carriers with application in the tissue engineering field targeting several biological tissues. The combination of both applications into a single material has proven to be very challenging though. The paper presents also some examples of commercially available natural-origin polymers with applications in research or in clinical use in several applications. As it is recognized, this class of polymers is being widely used due to their similarities with the extracellular matrix, high chemical versatility, typically good biological performance and inherent cellular interaction and, also very significant, the cell or enzyme-controlled degradability. These biocharacteristics classify the natural-origin polymers as one of the most attractive options to be used in the tissue engineering field and drug delivery applications.