Chronic low back pain (LBP) as a single condition has consistently held the top position with respect to the numbers of years lived with disability. Numerous attempts for alleviating LBP have been presented by stimulating the damaged intervertebral disc (IVD) to repair, but no consensus regarding the right therapeutical modality has been found. The main approaches have consisted in either injecting single cell suspensions (cell-based therapy) or delivering biomaterial matrices (scaffold-based therapy) to regain some of the IVD´s functionality. Still, LBP remains a redundant healthcare burden for our society, and searching for new and more ambitious therapeutic modalities to stimulate IVD repair is of high relevance.
DiskedInj proposes to tackle the issue of poor IVD regeneration through a novel strategy merging the advantage of both cell-based and scaffold-based options: the “third tissue engineering strategy”. The main objective of DiskedInj is to fabricate cellularized units based on human bone marrow stromal cells (hBMSCs) combined with polymeric biodegradable microscaffolds, to be used as building blocks, with an optimal design in terms of size and architecture, to maintain high cellular activities.
The proposed combination will not only protect the cells from external damages due to the presence of the scaffolds, but those small units will also exhibit high fusiogenic property and consequently, can self-assemble in situ shortly after their injection into the damaged or degenerated IVD. Our preliminary work has validated the possibility to produce high numbers of microscaffolds using multiphoton lithography, to cellularize them in a high throughput way, and to assemble them together to form a stable, large, and volume-wise controllable macrotissue. During this project, multiple micro-units will be produced and used as cellularized IVD-building blocks, while the amount to be injected can also be adapted to the size of the defect, offering first insight towards personalized therapy for IVD repair. To enhance the regenerative potential of our technology, we propose additionally to control the differentiation of the hBMSC-spheroids by functionalizing the polymeric microscaffolds carrying them with defined growth factors.
The technology to be developed during the DiskedInj project is way beyond the state of the art and we are convinced that, with the expertise gathered within this programme, DiskedInj will achieve unprecedented breakthrough in terms of quality of IVD repair. In terms of tasks, mathematical modelling will be involved early in the DiskedInj project to guide decision making of key factors, such as the optimal cellular density and the most suitable microscaffold design. As IVD degeneration is mostly caused by either pro-inflammatory condition or traumatological events, we will evaluate both the paracrine and autocrine activities of the hBMSCs spheroid-laden microscaffolds. Then, to assess the healing potential of our technology and to ensure that the outcomes will have a translational value, we selected suitable preclinical models well established by the partners, starting from in vitro cell culture to ex vivo organ models. The internal and external partners proposed in this project and their access to cutting-edge methods and equipment will be pivotal to be able to reach our aims.
We are convinced that our objective, even though being ambitious, is reachable due to the highly multidisciplinary and recognized experts brought together in the DiskedInj programme. As the workflow to be developed might be transposable after adaptation to other tissues or organs affected by chronic degeneration, DiskedInj represents an important step-stone, not only for the field of IVD regeneration, but for the wider field of regenerative medicine.
