Engineering patient-specific bioprinted constructs for treatment of degenerated intervertebral disc

Abstract

Lower back pain (LBP), which is strongly associated with intervertebral disc (IVD) degeneration, is one of the most frequently reported age- and work-related disorder in actual society, leading to a huge socio-economic impact worldwide. The current treatments have poor clinical outcomes and do not consider each patient needs. Thus, there is a growing interest in the potential of personalized cell-based tissue engineering (TE) approaches aimed to regenerate the damaged IVD and efficiently restore full disc function. In this work, a bioink composed by silk fibroin (SF) hydrogel combined with elastin was used to bioprint patient-specific substitutes mimicking IVD ultrastructure, in particular the outer region of the IVD (i.e. annulus fibrosus, AF). Following a reverse engineering approach, the proposed strategy makes use of a 3D model of AF obtained by semi-automatic morphological segmentation from magnetic resonance imaging dataset of human IVD. SF/elastin bioprinted scaffolds were characterized thoroughly in vitro, in terms of physico-chemical and biological performance. The bioprinted SF/elastin scaffolds were shown to possess structural and mechanical properties similar to the native AF and to support cell attachment and growth. Human adipose-derived stem cell cultured onto the SF/elastin bioprinted scaffolds were shown to adhere, proliferate and maintain metabolic activity and viability up to 21 days of culturing. The implantation of custom-made SF/elastin implants that best emulate a patient AF anatomy can potentially open up new personalized treatments for tackling IVD disorders by means of improving recovery time after surgery and helping to restore spine biofunctionality.