Intervertebral disc decellularisation: progress and challenges

Abstract

Intervertebral disc (IVD) degeneration and the consequent low-back pain (LBP) affect over 80 % of people in western societies, constituting a tremendous socio-economic burden worldwide and largely impairing patients’ life quality. Extracellular matrix (ECM)-based scaffolds, derived from decellularised tissues, are being increasingly explored in regenerative medicine for tissue repair. Decellularisation plays an essential role for host cells and antigen removal, while maintaining native microenvironmental signals, including ECM structure, composition and mechanical properties, which are essential for driving tissue regeneration. With the lack of clinical solutions for IVD repair/regeneration, implantation of decellularised IVD tissues has been explored to halt and/or revert the degenerative cascade and the associated LBP symptoms. Over the last few years, several researchers have focused on the optimisation of IVD decellularisation methods, combining physical, chemical and enzymatic treatments, in order to successfully develop a cell-free matrix. Recellularisation of IVD-based scaffolds with different cell types has been attempted and numerous methods have been explored to address proper IVD regeneration. Herein, the advances in IVD decellularisation methods, sterilisation procedures, repopulation and biocompatibility tests are reviewed. Additionally, the importance of the donor profile for therapeutic success is also addressed. Finally, the perspectives and major hurdles for clinical use of the decellularised ECM-based biomaterials for IVD are discussed. The studies reviewed support the notion that tissue-engineering-based strategies resorting to decellularised IVD may represent a major advancement in the treatment of disc degeneration and consequent LBP.

Nucleus pulposus cells degeneration model: a necessary way to study intervertebral disc degeneration

“…It is necessary to further explore the optimal conditions and optimize the induction method in the future. Intervertebral disc degeneration resulting in pain and abnormal function of lower limbs, has become a serious problem in modern society, causing a huge economic burden [117] . Traditional surgery and drug therapy cannot satisfy the fundamental treatment goals.…”

Endplate role in the degenerative disc disease: A brief review

“…The approaches targeting the reconstruction or regeneration of the intervertebral disc, on the other hand, are still evolving, thus being in the experimental phase of clinical use, mainly in the in vitro settings. Here, the tissue engineering strategies encompass the use of implantable biomaterials, nanofibers and implantable cells, since the degenerative processes are not limited to the nucleus or annulus only but also include the terminal plate[ 112 - 114 ]. The knowledge of the intervertebral disc biomechanical properties, ageing and degeneration and the design of novel treatment strategies are crucial for the design of a therapeutic approach.…”

“…It is ubiquitous in the human body, relatively easy obtainable in larger quantities and with low immunogenicity. At the same time, atelocollagen can be acquired from collagen by preparation with the enzyme pepsin[ 114 - 116 ]. The atelocollagen has excellent bioimmunological properties and is therefore one of the most commonly used materials for tissue matrices.…”

“…The atelocollagen has excellent bioimmunological properties and is therefore one of the most commonly used materials for tissue matrices. The honeycomb-like organisation of the atelocollagen also offers excellent mechanical stability and provides a scaffold for optimal cell ingrowth in proliferation[ 114 , 115 ].…”

Decellularized extracellular matrix-based scaffold and hypoxic priming: A promising combination to improve the phenotype of degenerate intervertebral disc cells

“…On the one hand, the use of decellularized matrix is part of studies aimed at exploring new opportunities for the development of biological IVD scaffolds/biomaterials [23][24][25][26]. Although attempts of organ decellularization have recently been performed on bovine, porcine and in a few cases also human IVD [27][28][29], however disc decellularization remains a challenge due to the dense nature of the tissue, which can be an obstacle to decellularization procedures, the scarcity of tissue donors, concerns of disease transmission, and inaccessibility to the healthy human IVD for ethical reason [29]. In this scenario, the use of the decellularized matrix from perinatal tissues such as the Wharton's Jelly of umbilical cord can represent a valid alternative to the production and use of decellularized matrix from the disc.…”