Abstract
The central nervous system (CNS), consisting of the brain and spinal cord, regulates the mind and functions of the organs. CNS diseases, leading to changes in neurological functions in corresponding sites and causing long-term disability, represent one of the major public health issues with significant clinical and economic burdens worldwide. In particular, the abnormal changes in the extracellular matrix under various disease conditions have been demonstrated as one of the main factors that can alter normal cell function and reduce the neuroregeneration potential in damaged tissue. Decellularised extracellular matrix (dECM)-based biomaterials have been recently utilised for CNS applications, closely mimicking the native tissue. dECM retains tissue-specific components, including proteoglycan as well as structural and functional proteins. Due to their unique composition, these biomaterials can stimulate sensitive repair mechanisms associated with CNS damages. Herein, we discuss the decellularisation of the brain and spinal cord as well as recellularisation of acellular matrix and the recent progress in the utilisation of brain and spinal cord dECM.
Highlights
The human central nervous system (CNS) is a highly complex biological tissue, comprised of neurons and support cells called glia (Refs 1, 2)
Glial cells produce and assemble a highly organised extracellular matrix (ECM) that makes up approximately 20% of the total volume of the adult CNS (Refs 3, 4, 5)
Inflammatory responses to prevent the expansion of tissue damage after traumatic injuries or during neurodegenerative diseases alter the composition of the CNS ECM and result in remodelling (Ref. 12)
Summary
The human central nervous system (CNS) is a highly complex biological tissue, comprised of neurons and support cells called glia (Refs 1, 2). MSCs are widely studied adult SCs as part of therapeutic cell transplantation to repair failed tissues and organs for regenerative medicine and treatment of various diseases such as Parkinson’s, and ischemic stroke with the capability to replace and regenerate damaged tissues with no immunogenic effect (Refs 32, 33, 34). Various studies have shown that neural, bone marrow and adipose-derived MSCs can be induced to express a neuronal cell phenotype, trans/differentiate to neural precursors and/or mature neurons and promote neuroprotection and neurogenesis in vitro under specific experimental conditions for the treatment of CNS diseases (Refs 28, 35, 36, 37, 38). Apart from highlighted applications, dECM-based biomaterials have been utilised in various tissue engineering approaches such as support materials for 3D cell culture studies (e.g., brain organoids), injectable hydrogels for the repair of tissue damage, carriers for drug and growth factors, composite materials for neuroregeneration, substrates mimicking native tissue microenvironment in organ-on-a-chip platforms, and bioinks for 3D bioprinting (Fig. 1). This review focuses on the physical, chemical and biological methods for decellularisation of brain and spinal cord ECM in the context of CNS applications and discusses innovative applications
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