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Current therapies for treating brain injuries, including stroke and traumatic brain injury, are designed to modify symptoms pharmacologically but do not promote full structural and functional regeneration of the brain. Integrating the merits of cell, biomaterials scaffolds and pharmaceutical therapies, biodegradable scaffold-facilitated cell therapy is a promising multifaceted approach to modify the local injury environment, and also to promote transplanted cell replacement and endogenous regeneration mechanisms. Collagen is an attractive candidate for providing a temporary supportive matrix for cell and drug delivery to the brain. With good biocompatibility, design flexibility and biomimetic properties of the natural extracellular matrix, collagen-based cell transplantation has demonstrated therapeutic potentials in preclinical studies of brain injury. In this review, we will discuss the properties and design considerations of collagen-based scaffolds for brain tissue engineering. Also, the current developments of collagen-based scaffolds in conveying different sources of cells, such as mesenchymal stem cells, neural stem/progenitor cells, embryonic stem cells and induced pluripotent stem cells and derivatives to the brain will be illustrated. Advanced understanding in the interactions between collagen, cells and the local injury environment has greatly expanded the potential of these biomimetic systems to repair and regeneration the brain.
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