Bioprinting Complex Cartilaginous Structures with Clinically Compliant Biomaterials

Bioprinting is an emerging technology for the fabrication of patient‐specific, anatomically complex tissues and organs. A novel bioink for printing cartilage grafts is developed based on two unmodified FDA‐compliant polysaccharides, gellan and alginate, combined with the clinical product BioCartilage (cartilage extracellular matrix particles). Cell‐friendly physical gelation of the bioink occurs in the presence of cations, which are delivered by co‐extrusion of a cation‐loaded transient support polymer to stabilize overhanging structures. Rheological properties of the bioink reveal optimal shear thinning and shear recovery properties for high‐fidelity bioprinting. Tensile testing of the bioprinted grafts reveals a strong, ductile material. As proof of concept, 3D auricular, nasal, meniscal, and vertebral disk grafts are printed based on computer tomography data or generic 3D models. Grafts after 8 weeks in vitro are scanned using magnetic resonance imaging and histological evaluation is performed. The bioink containing BioCartilage supports proliferation of chondrocytes and, in the presence of transforming growth factor beta‐3, supports strong deposition of cartilage matrix proteins. A clinically compliant bioprinting method is presented which yields patient‐specific cartilage grafts with good mechanical and biological properties. The versatile method can be used with any type of tissue particles to create tissue‐specific and bioactive scaffolds.     

Porous Structures: In situ Porous Structures: A Unique Polymer Erosion Mechanism in Biodegradable Dipeptide‐Based Polyphosphazene and Polyester Blends Producing Matrices for Regenerative Engineering (Adv. Funct. Mater. 17/2010)

Synthetic biodegradable polymers serve as temporary substrates that accommodate cell infiltration and tissue in‐growth in regenerative medicine. To allow tissue in‐growth and nutrient transport, traditional three‐dimensional (3D) scaffolds must be prefabricated with an interconnected porous structure. Here we demonstrated for the first time a unique polymer erosion process through which polymer matrices evolve from a solid coherent film to an assemblage of microspheres with an interconnected 3D porous structure. This polymer system was developed on the highly versatile platform of polyphosphazene‐polyester blends. Co‐substituting a polyphosphazene backbone with both hydrophilic glycylglycine dipeptide and hydrophobic 4‐phenylphenoxy group generated a polymer with strong hydrogen bonding capacity. Rapid hydrolysis of the polyester component permitted the formation of 3D void space filled with self‐assembled polyphosphazene spheres. Characterization of such self‐assembled porous structures revealed macropores (10–100 μm) between spheres as well as micro‐ and nanopores on the sphere surface. A similar degradation pattern was confirmed in vivo using a rat subcutaneous implantation model. 12 weeks of implantation resulted in an interconnected porous structure with 82–87% porosity. Cell infiltration and collagen tissue in‐growth between microspheres observed by histology confirmed the formation of an in situ 3D interconnected porous structure. It was determined that the in situ porous structure resulted from unique hydrogen bonding in the blend promoting a three‐stage degradation mechanism. The robust tissue in‐growth of this dynamic pore forming scaffold attests to the utility of this system as a new strategy in regenerative medicine for developing solid matrices that balance degradation with tissue formation.