3-D printed flexible hybrids for tissue regeneration

Abstract

Tissue regeneration is a key function of the body, but often tissues are subject to damage that they are unable to self-heal. The repair can be supported by a scaffold, which is commonly a 3D porous temporary template that substitutes the damaged tissue and guides the growth of healthy tissue while bioresorbing. Successful scaffolds should satisfy several requirements, including interconnected porosity, sufficient mechanical properties, and biodegradability at a rate matching tissue regrowth. Covalently-bonded sol-gel inorganic/organic hybrids are interpenetrating co-networks of bioactive glass and polymers intimately linked at the molecular level, designed to provide tailored mechanical properties and congruent degradation. This project aimed to develop new silica/polycaprolactone (SiO2/PCL) hybrid scaffolds for bone or cartilage regeneration. The covalent bond between PCL and silica was successfully achieved using (3-glycidoxypropyl)trimethoxysilane (GPTMS) as a coupling agent. This led to a novel synthesis that combined the sol-gel process with in situ ring-opening polymerisation of the solvent (tetrahydrofuran), resulting in innovative silica/polytetrahydrofuran/PCL (SiO2/PTHF/PCL) hybrids with unprecedented features. They showed tailorable mechanical properties in a broad range of compositions (2.5-63.4 wt.% inorganic), from polymer-like to glass-like behaviour with excellent flexibility and ability to recover the deformation. Hybrids with SiO2 <40 wt.% maintained their mechanical properties in wet environments; they also unexpectedly showed the intrinsic potential to autonomously self-heal when damaged in dry conditions. 3D grid-like hybrid scaffolds containing ~24 wt.% inorganic were successfully fabricated through 3D extrusion printing from sol-gel process. This technique relies on the gradual increase of viscosity occurring during gelation, which makes the viscous sol a suitable ink for direct extrusion within a limited time window. The obtained scaffolds showed mechanical properties similar to native cartilage and were proven to stimulate the production of collagen Type II, typical of hyaline cartilage, during chondrocyte culture. Therefore, SiO2/PTHF/PCL hybrid scaffolds have great potential for articular cartilage regeneration.