Current strategies for treatment of intervertebral disc degeneration: substitution and regeneration possibilities

Background: Intervertebral disc degeneration has an annual worldwide socioeconomic impact masked as low back pain of over 70 billion euros. This disease has a high prevalence over the working age class, which raises the socioeconomic impact over the years. Acute physical trauma or prolonged intervertebral disc mistreatment triggers a biochemical negative tendency of catabolic-anabolic balance that progress to a chronic degeneration disease. Current biomedical treatments are not only ineffective in the long-run, but can also cause degeneration to spread to adjacent intervertebral discs. Regenerative strategies are desperately needed in the clinics, such as: minimal invasive nucleus pulposus or annulus fibrosus treatments, total disc replacement, and cartilaginous endplates decalcification. Main Body: Herein, it is reviewed the state-of-the-art of intervertebral disc regeneration strategies from the perspective of cells, scaffolds, or constructs, including both popular and unique tissue engineering approaches. The premises for cell type and origin selection or even absence of cells is being explored. Choice of several raw materials and scaffold fabrication methods are evaluated. Extensive studies have been developed for fully regeneration of the annulus fibrosus and nucleus pulposus, together or separately, with a long set of different rationales already reported. Recent works show promising biomaterials and processing methods applied to intervertebral disc substitutive or regenerative strategies. Facing the abundance of studies presented in the literature aiming intervertebral disc regeneration it is interesting to observe how cartilaginous endplates have been extensively neglected, being this a major source of nutrients and water supply for the whole disc. Conclusion: Severalinnovative avenues for tackling intervertebral disc degeneration are being reported â from acellular to cellular approaches, but the cartilaginous endplates regeneration strategies remain unaddressed. Interestingly, patient-specific approaches show great promise in respecting patient anatomy and thus allow quicker translation to the clinics in the near future.The authors would like to acknowledge the support provided by the Portuguese Foundation for Science and Technology (FCT) through the project EPIDisc (UTAP-EXPL/BBBECT/0050/2014), funded in the Framework of the “International Collaboratory for Emerging Technologies, CoLab”, UT Austin|Portugal Program. The FCT distinctions attributed to J. Miguel Oliveira (IF/00423/2012 and IF/01285/ 2015) and J. Silva-Correia (IF/00115/2015) under the Investigator FCT program are also greatly acknowledged.info:eu-repo/semantics/publishedVersio

Composite bioscaffolds incorporating decellularized ECM as a cell-instructive component within hydrogels as in vitro models and cell delivery systems

© Springer Science+Business Media New York 2017. Decellularized tissues represent promising biomaterials, which harness the innate capacity of the tissue-specific extracellular matrix (ECM) to direct cell functions including stem cell proliferation and lineage-specific differentiation. However, bioscaffolds derived exclusively from decellularized ECM offer limited versatility in terms of tuning biomechanical properties, as well as cell–cell and cell–ECM interactions that are important mediators of the cellular response. As an alternative approach, in the current chapter we describe methods for incorporating cryo-milled decellularized tissues as a cell-instructive component within a hydrogel carrier designed to crosslink under mild conditions. This composite strategy can enable in situ cell encapsulation with high cell viability, allowing efficient seeding with a homogeneous distribution of cells and ECM. Detailed protocols are provided for the effective decellularization of human adipose tissue and porcine auricular cartilage, as well as the cryo-milling process used to generate the ECM particles. Further, we describe methods for synthesizing methacrylated chondroitin sulphate (MCS) and for performing UV-initiated and thermally induced crosslinking to form hydrogel carriers for adipose and cartilage regeneration. The hydrogel composites offer great flexibility, and the hydrogel phase, ECM source, particle size, cell type(s) and seeding density can be tuned to promote the desired cellular response. Overall, these systems represent promising platforms for the development of tissue-specific 3-D in vitro cell culture models and in vivo cell delivery systems