Biologic Scaffold for CNS Repair

Abstract

Injury to the CNS typically results in significant morbidity and endogenous repair mechanisms are limited in their ability to restore fully functional CNS tissue. Biologic scaffolds composed of individual purified components have been shown to facilitate functional tissue reconstruction following CNS injury. Extracellular matrix scaffolds derived from mammalian tissues retain a number of bioactive molecules and their ability for CNS repair has recently been recognized. In addition, novel biomaterials for dural mater repairs are of clinical interest as the dura provides barrier function and maintains homeostasis to CNS. The present article describes the application of regenerative medicine principles to the CNS tissues and dural mater repair. While many approaches have been exploring the use of cells and/or therapeutic molecules, the strategies described herein focus upon the use of extracellular matrix scaffolds derived from mammalian tissues that are free of cells and exogenous factors.

Restoring Mucosal Barrier Function and Modifying Macrophage Phenotype with an Extracellular Matrix Hydrogel: Potential Therapy for Ulcerative Colitis

“…The findings of the present study are consistent with, and analogous to, the known mechanisms by which ECM-based approaches facilitate the constructive remodeling of injured tissues in other anatomic locations [5,26,27,28,29,30]. Specifically, ECM materials derived via decellularization of a variety of allogeneic or xenogeneic source tissues have been shown to induce a phenotypic transition from the proinflammatory macrophage and lymphocyte phenotype toward a regulatory, "anti-inflammatory" and healing phenotype [9,31,32,33], and to promote endogenous stem/progenitor cell activation and recruitment [11,29,34,35].…”

Concentration-dependent rheological properties of ECM hydrogel for intracerebral delivery to a stroke cavity

“…1C). Detailed neurosurgical planning, in combination with delivery of an appropriate concentration of biomaterial, is hence required to maximize the potential of biomaterial therapy for CNS repair [4]. …”

“…To achieve retention of injected cells within the lesion cavity, it is essential to provide a permissive structural and functional microenvironmental niche [6–9]. Such niche support may be achieved by biomaterials specifically engineered to be compatible with neural tissue and amenable to delivery through a small gauge needle for intracerebral injections, with minimal damage to healthy tissue [1,4,10]. Hydrogel forms of naturally occurring biomaterials composed of extracellular matrix (ECM) show in vitro chemoattraction and differentiation stimuli for neural stem cells [11–13].…”

Diamagnetic chemical exchange saturation transfer (diaCEST) affords magnetic resonance imaging of extracellular matrix hydrogel implantation in a rat model of stroke

“…Upon tissue decellularization, these ECM molecules are retained and can be used for bioscaffolding purposes [7, 42]. Non-invasive imaging of ECM molecules has mainly focussed on glycosaminoglycans (GAGs) due to their presence in intervertebrate discs and the clinical need to improve our ability to visualize its degradation.…”