Supramolecular design of multitactic 3D polymeric biomaterials for spinal cord repair

Description

Spinal cord injury (SCI) represents one of the leading causes of disability worldwide , being characterized by a permanent loss of motor function and sensory perception owing to the complex pathophysiology and inability of the central nervous system (CNS) to self-regenerate. Currently, the most common therapeutic approaches involve the systemic administration of steroids and surgical decompression of the spine to prevent further damage. However, these treatments fail to repair the damaged neural tissue. One promising direction for SCI therapy is the modulation of the local microenvironment to promote neuroprotection and neurogenesis. Functional biomaterials have great potential for remodeling the SCI microenvironment by providing native extracellular matrix (ECM)-mimetic biophysical cues to support to cells, but also biochemical and biomechanical cues for directing tissue growth. Biomaterials can work as a support for enabling axonal regeneration, or they can be modified to serve as carriers of cells, drugs, or other bioactive molecules to increase their effect in remodeling the hostile SCI environment. Consequently, there is a critical need for innovative, biomimetic scaffolds that combine structural support with biochemical and biomechanical cues to mimic the native neural tissue. The SUPRANEURO project aims to develop a biomimetic, multicomponent supramolecular biomaterial-based neural guidance conduit to fully support spinal cord regeneration . The main goal is to leverage natural polymeric biomaterials, bioactive neural ECM-mimetic self-assembling peptides, micropatterned architectures, and controlled neurotrophic factor delivery to promote neural tissue regeneration . This approach will rely on three major objectives . First, i) the development of biocompatible and biodegradable free-standing (FS) multilayered membranes denoting bioactive cues and anisotropic microtopographies, which will provide both a topographical and mechanical framework for directing neuronal tissue growth. Secondly, ii) the sustained release of brain-derived neurotrophic factor (BDNF), incorporated into the conduit to support neural precursor cells (NPCs) survival and differentiation into neuronal phenotypes. Thirdly, iii) the design of a fully 3D functional neural guidance conduit that integrates both structural biomimicry, biochemical and biomechanical support, enhancing its potential for SCI recovery. SUPRANEURO ’s joins a highly inter- and multidisciplinary team consisting of expert scientists in chemistry, biochemistry, material science and engineering, biomaterials and cell biology fields. Our collective mastered experience and efforts in developing natural polymer-based biomaterials, fabricating micropatterned structures, and conducting stem cell culture in advanced 3D systems will be critical to ensure the successful execution and implementation of the project. The team is well-equipped with background knowledge, experience, expertise, and technical skills to tackle the challenges of developing a biomimetic neural biomaterial conduit that can effectively support and address SCI repair. What sets the SUPRANEURO project apart from traditional approaches is its fully integrated and innovative approach to SCI treatment. Specifically, the approach relies on three key elements. First, the use of non-immunogenic, biocompatible and biodegradable natural polymeric biomaterials , such chitosan and hyaluronic acid, and self-assembling peptides, ensuring FS membrane’s biocompatibility, biodegradability, and bioactive properties for neural regeneration. Secondly, the innovative biomimetic anisotropic microarchitecture that will play a critical role in directing axonal growth and improve functional connectivity and recovery. Thirdly, the incorporation of BDNF as an intrinsic building block of the FS multilayered membranes , increasing the loading efficiency and local sustained release, will promote cell survival and growth. This controlled release biomaterial system will ensure a continuous and gradual supply of neurotrophic factors. The project will move forward current state-of-the-art knowledge and advance regenerative medicine therapies by proposing a pioneering, fully integrated, safe, robust and advanced 3D bioactive biomaterial-based neural guidance conduit which will enhance the understanding of nervous tissue repair and tackle SCI. Ultimately, SUPRANEURO seeks to improve treatments for SCI and related nervous system conditions, offering the potential to transform currently available methods, and improve the quality and life expectancy of SCI patients SCI and, simultaneously, reduce the healthcare costs. The SUPRANEURO project will foster advanced training of students and researchers in the emerging field of supramolecular polymeric biomaterials-based devices and therapies for SCI repair.