Extracellular matrix from umbilical cord as component for bioscaffolds tailored to intervertebral disc diseases
Abstract:
The main aim of the present proposal is the development of a new class of composite biomaterials (i.e. scaffolds of different compositions) designed for the treatment of degenerate intervertebral disc (IVD). In this respect it is noteworthy to mention that IVD damages represent the major cause of chronic low back and neck pain which affects over 70% of the world’s population and is the most prevalent form of disability with a huge socioeconomic burden.
Although some tissue engineering strategies have been proposed, currently, restoration of the healthy IVD microenvironment remains a great challenge.
It is well known that the continuous breakdown of extracellular matrix (ECM) components is one of the predominant phenomena in IVD degenerative conditions: to find new solutions the current project focuses on the design of scaffolds containing, as an “active” constituent, a decellularized ECM. The decellularized umbilical cord Wharton’s Jelly matrix (DWJM) was chosen based on our preliminary results. The rationale for this strategic choice is that the molecular constituents of the DWJM are very similar to those of the IVD, and DWJM is effective in restoring the chondrogenic-like phenotype lost by degenerate IVD cells.
In view of possible therapeutic applications of DWJM-based scaffolds in IVD degeneration, the strategy summarized below will be used.
With the aim to obtain an entire spectrum of composite scaffolds tailored to different injection/implantation modalities, the DWJM will be combined with other natural and synthetic biomaterials such as marine polysaccharides, gelatin/collagen, polyesters, tri-block-copolymers, bioglasses (RU1). Combining different percentages of the biomaterials with DWJM a vast spectrum of physical states and geometries will be produced, spanning from liquid, to low viscosity hydrogels, to semisolid elastic materials. Much attention will be also paid to studying the porosity of the scaffolds in view of an appropriate recellularization. The different scaffolds will be combined with human IVD cells (i.e. seeded or encapsulated) and the cell response, in terms of attachment, proliferation, differentiation and matrix deposition will be investigated up to at least 3 weeks of culture (RU1 and RU2) in 2% oxygen tension.
Furthermore, the release of anti-inflammatory and pro-differentiating molecules will be studied both as soluble factors and as extracellular vesicles in biomaterials combined or not with the cells (RU2). This will help to understand the beneficial of the different biomaterials both in recreating in vitro a native IVD microenvironment or in inducing the combined cells to secrete anabolic factors promoting the endogenous repair.
The production of bioinks based on DWJM will be also investigated, by 3D-bioprinting and electron microscopy facilities (Subunit of RU1), with the aim to produce scaffolds for future applications inspired by the principle of "personalized medicine".
Although some tissue engineering strategies have been proposed, currently, restoration of the healthy IVD microenvironment remains a great challenge.
It is well known that the continuous breakdown of extracellular matrix (ECM) components is one of the predominant phenomena in IVD degenerative conditions: to find new solutions the current project focuses on the design of scaffolds containing, as an “active” constituent, a decellularized ECM. The decellularized umbilical cord Wharton’s Jelly matrix (DWJM) was chosen based on our preliminary results. The rationale for this strategic choice is that the molecular constituents of the DWJM are very similar to those of the IVD, and DWJM is effective in restoring the chondrogenic-like phenotype lost by degenerate IVD cells.
In view of possible therapeutic applications of DWJM-based scaffolds in IVD degeneration, the strategy summarized below will be used.
With the aim to obtain an entire spectrum of composite scaffolds tailored to different injection/implantation modalities, the DWJM will be combined with other natural and synthetic biomaterials such as marine polysaccharides, gelatin/collagen, polyesters, tri-block-copolymers, bioglasses (RU1). Combining different percentages of the biomaterials with DWJM a vast spectrum of physical states and geometries will be produced, spanning from liquid, to low viscosity hydrogels, to semisolid elastic materials. Much attention will be also paid to studying the porosity of the scaffolds in view of an appropriate recellularization. The different scaffolds will be combined with human IVD cells (i.e. seeded or encapsulated) and the cell response, in terms of attachment, proliferation, differentiation and matrix deposition will be investigated up to at least 3 weeks of culture (RU1 and RU2) in 2% oxygen tension.
Furthermore, the release of anti-inflammatory and pro-differentiating molecules will be studied both as soluble factors and as extracellular vesicles in biomaterials combined or not with the cells (RU2). This will help to understand the beneficial of the different biomaterials both in recreating in vitro a native IVD microenvironment or in inducing the combined cells to secrete anabolic factors promoting the endogenous repair.
The production of bioinks based on DWJM will be also investigated, by 3D-bioprinting and electron microscopy facilities (Subunit of RU1), with the aim to produce scaffolds for future applications inspired by the principle of "personalized medicine".
Dettagli progetto:
Referente scientifico: Piva Maria Roberta
Fonte di finanziamento: Bando PRIN 2022
Data di avvio: 28/09/2023
Data di fine: 28/09/2025
Contributo MUR: 121.778 €
Cofinanziamento UniFe: 38.395 €
Partner:
- Università degli Studi di FERRARA (capofila)
- Università degli Studi di PADOVA