Periodic Reporting for period 1 - iDISC (Rejuvenation of the Intervertebral Disc Using Self-Healing Biomimetic Extracellular Matrix Biomaterial Tissue Adhesives)
Período documentado: 2024-04-01 hasta 2025-09-30
Lower back pain is a global epidemiological and socioeconomic problem. This project envisions a future whereby patients with degenerated intervertebral discs are injected with a self-healing biomimetic adhesive biomaterial which can restore both the biochemical and biomechanical properties to native tissue levels. Current surgical procedures do not replace herniated tissue from the central nucleus pulposus or repair the annulus fibrosus (outer ring of tissue), which can lead to accelerated degeneration, reherniation and recurrent pain. Spinal fusion, whereby the compromised or degenerated tissue is removed, and the vertebral segments are fused together, does not restore biomechanical function leading to degeneration of adjacent discs with long-term failure rates as high as 40%. My lab has developed a biomimetic injectable hydrogel (iDISC) consisting of the main components of native disc tissue that can be tailored to match the biochemical and biomechanical properties of native disc tissue. In addition, the iDISC hydrogel demonstrates self-healing and adhesive properties to facilitate tissue integration and exhibits excellent cell biocompatibility. The objective of this project was to perform in depth in vitro characterisation (WP1), multiaxial biomechanical testing (WP2), pre-clinical evaluation (WP3) and marketing and commercialisation evaluation (WP4). The development of these injectable biomimetic hydrogel systems may facilitate earlier interventions aimed at halting the degenerative process, restore natural biomechanical function, enhancing patient accessibility, improving quality of life, reduce healthcare expenses and lost productivity in the European Union. The platform technology and knowledge generated through this research are beyond the current state-of-the-art and will provide a significant transformative scientific and clinical step change opening new horizons in minimally invasive spine treatment strategies.
The iDISC platform has been developed as an injectable hydrogel system designed to replicate the biochemical and mechanical properties of the native intervertebral disc (IVD), serving as both a filler and a regenerative hydrogel. The system includes formulations targeting the nucleus pulposus (NP) and annulus fibrosus (AF), providing structural reinforcement, bioadhesion, and cellular support within degenerated discs. The AF hydrogel was synthesised and combined with AF extracellular matrix nanofibres (AFNF). The fibrous AFNF network significantly enhanced mechanical performance, with the AFNF formulation achieving an aggregate modulus within the physiological range of native AF tissue. Tensile testing confirmed improvements in strength and modulus comparable to standard clinical adhesives. The NP hydrogel, developed using modified NP ECM, exhibited biomechanical and biochemical properties similar to native NP tissue. Its bioadhesive strength was comparable to fibrin glue, supported by interactions with tissue proteins. Both AF and NP hydrogels exhibited good biocompatibility, supporting cell viability and disc-specific ECM production. Injection tests confirmed minimal shear-induced damage to encapsulated cells, while histology analysis revealed collagen type II and Sox9 expression consistent with disc regeneration. Ex vivo evaluation demonstrated the hydrogels’ ability to adhere securely and withstand physiological compression and torsion in bovine disc models. In degenerated goat disc models, NP and cell-laden hydrogels maintained cell viability and integrated seamlessly with native tissue confirming their potential as cell delivery vehicles and biomechanical stabilisers. Preclinical evaluation in a caprine disc degeneration model, confirmed the hydrogel’s safety over four months post-implantation.
A market assessment has been completed to evaluate the commercial potential of the iDISC platform. The analysis identified a clear market gap for regenerative biomaterials targeting intervertebral disc repair, supporting the feasibility of translation into a clinical product. A European patent application titled “An extracellular-matrix-derived gel composition” has also been filed to protect the intellectual property arising from the ERC INTEGRATE and ERC Proof of Concept (PoC) iDISC projects. The data generated so far demonstrate strong commercialisation potential, and future steps will focus on conducting longer-term animal studies under GMP conditions to validate safety and efficacy. Plans are underway to establish a spin-out company and initiate fundraising to support regulatory translation and product development. In summary, the iDISC project has successfully developed a series of ECM-derived injectable hydrogels for intervertebral disc regeneration, combining mechanical performance, bioadhesion, and cellular compatibility. The system shows promise as a translational platform for minimally invasive treatment of disc degeneration. Current work is directed toward process optimisation, scale-up, GMP validation, and commercial development for future clinical application.
A market assessment has been completed to evaluate the commercial potential of the iDISC platform. The analysis identified a clear market gap for regenerative biomaterials targeting intervertebral disc repair, supporting the feasibility of translation into a clinical product. A European patent application titled “An extracellular-matrix-derived gel composition” has also been filed to protect the intellectual property arising from the ERC INTEGRATE and ERC Proof of Concept (PoC) iDISC projects. The data generated so far demonstrate strong commercialisation potential, and future steps will focus on conducting longer-term animal studies under GMP conditions to validate safety and efficacy. Plans are underway to establish a spin-out company and initiate fundraising to support regulatory translation and product development. In summary, the iDISC project has successfully developed a series of ECM-derived injectable hydrogels for intervertebral disc regeneration, combining mechanical performance, bioadhesion, and cellular compatibility. The system shows promise as a translational platform for minimally invasive treatment of disc degeneration. Current work is directed toward process optimisation, scale-up, GMP validation, and commercial development for future clinical application.
The iDISC platform advances the state of the art in intervertebral disc regeneration by integrating biochemical mimicry, mechanical reinforcement, and bioadhesion within a single injectable hydrogel system. Derived from tissue-specific extracellular matrix components, the hydrogels replicate the native properties of NP and AF tissues, enabling both structural sealing and biological regeneration. Compared to existing adhesives or hydrogels, iDISC demonstrates superior mechanical strength, biocompatibility, and integration with native tissue. These results have strong clinical potential for minimally invasive treatment of disc degeneration, reducing reherniation and the need for spinal fusion. To ensure further uptake, key steps include longer-term in vivo validation, manufacturing scale-up, regulatory engagement, and investment for commercialisation. A European patent has been filed to protect the technology, supporting future translation and market readiness.