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Tissue engineering of nervous system
The document discusses tissue engineering approaches for the nervous system. It begins with an introduction to the anatomy and limited regenerative capacity of the central and peripheral nervous systems. For peripheral nerve injuries, the current gold standard treatment is autologous nerve grafts, but these have limitations. Alternative approaches discussed include the use of nerve guides containing matrices and scaffolds to bridge gaps and guide axon regeneration. Factors like scaffold composition and geometry, inclusion of cells and growth factors, and degradation properties can influence how well scaffolds support regeneration across critical gaps in nerves. The document reviews considerations for scaffold and matrix design and various strategies for incorporating growth-promoting components in peripheral nerve engineering.
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Tissue engineering of nervous system
- 1. TISSUE ENGINEERING OF NERVOUSSYSTEM Presented by S.Shashank Chetty 2nd year M.Tech, NAST
- 2. Objectives: Introduction to Nervous System. Anatomyand Origin of Peripheral nerve System. Autologous nerve grafts (autograft) Nerve guides critical gap length in peripheral nerves. Matrices and scaffolds selection of approaches Summary
- 4. Introduction The loss oftouch, sight, hearing or movement often results from diseases or injuries to the nervous system. The retina, cochlear, spinal cord, brain and peripheral nerve have very different molecular and cellular environments, and tissue engineering within each requires different strategies. The limited regeneration in the central nervous system (CNS) is primarily due to the different cellular and molecular environment, and less to the internal properties of the corresponding neurons. Scaffolds and matrices in the nervous system, therefore, provide a substrate for axonal growth that has efficacy even in the inhibitory CNS environment. The most popular approach in peripheral nerve tissue engineering involves in vivo implantation of artificial scaffolds and substrates that will guide naturally regenerating axons to the distal segment.
- 5. Peripheral nerve Peripheral nerveinjuries (PNI) can lead to lifetime loss of function and disfigurement. Figure: Anatomy of the peripheral nerve. The axons from the selected fascicle are indicated in yellow. The Schwann cell myelin sheath is drawn to demonstrate the wrapping of the cell body around the axon; however, the myelin is compact and only a single dark ring is typically seen with histology (right).
- 6. Ependymal cells • lineventricles of brain & central canal of spinal cord • produce, monitor & help circulate CSF (cerebrospinal fluid) Astrocytes • create supportive framework for neurons • create “blood-brain barrier” • monitor & regulate interstitial fluid surrounding neurons • secrete chemicals for embryological neuron formation • stimulate the formation of scar tissue secondary to CNS injury Microglia • “brain macrophages” • phagocytize cellular wastes & pathogens Oligodendrocytes • create myelin sheath around axons of neurons in the CNS. Myelinated axons transmit impulses faster than unmyelinated axons Schwann cells • surround all axons of neurons in the PNS creating a neurilemma around them. Neurilemma allows for potential regeneration of damaged axons • creates myelin sheath around most axons of PNS
- 7. Autologous nerve grafts(autograft) Figure: End-to-end suturing of peripheral nerves. Alignment of the fascicles is critical in successful regeneration and microsurgical techniques have been developed to optimize this surgery.
- 8. Use of tubes(nerve guides) in the PNS Figure: Sequence of events in empty silicone nerve guides. Initially, fluid and cytokines fill up the nerve guide (a), followed by the formation of a fibrin matrix inside the lumen which initially supports invading fibroblasts (blue) (b), followed by Schwann cells (green) and axons (red) (c), which eventually penetrate to the distal stump. The regenerated nerve usually is thinner in the middle of the bridge (yellow). Figure: The chance of successful reinnervation with nerve guides is dramatically reduced once an injury gap reaches a certain value. This length, termed the critical gap length, L C, is where successful regeneration occurs 50% of the time.
- 9. Basic Nerve Guide Requirements • Sterilizable •Porous • Low antigenicity • Persists during regeneration • Biodegradable over long-term • Resists compression or collapse • Pliable (not too rigid) • Contains regeneration stimuli
- 10. In PNS, theproximal segment may be able to regenerate and reestablish nerve function. Proliferating Schwann cells, macrophages, and monocytes work together to remove myelin debris, release neruotrophins, and lead axons toward their synaptic targets, resulting in restored neuronal function. In CNS, an impermeable glial scar composed of myelin, cellular debris, astrocytes, oligodendrocytes, and microglia formed. Regeneration neurons are blocked from reaching their synaptic target.
- 11. Matrices and scaffolds Peripheralnerve tissue engineering matrices have either oriented or random structures, while scaffolds predominantly have an oriented morphology. Figure: Selected examples of the critical gap length gap, LC, adapted from Yannas and Hill (2004) for the rat sciatic nerve. Empty silicone nerve guides (a) have a L C of 9.7 mm and the introduction of a collagen–GAG matrix (b) increases the L C to at least 14.8 mm with a L of 5.1 mm. When oriented fibrin matrices are used (c), this results in a L of at least 4.7 mm when compared to the same, nonoriented matrices. Degradable collagen nerve guides (d) have a L of at least 5.4 mm compared to silicone tubes. When polyamide or collagen fibers are introduced (e), the L is at least 7.4 mm compared to empty nerve guides, while Schwann cells (f) result in a similar L value of 7.4 mm, compared to nerve guides filled with phosphate-buffered saline. Note: the shift length ( L ) is the result of the therapy – not necessarily compared to empty nerve guides .
- 12. First, there isthe scaffold, this being a microporous, usually three dimensional, structure, within which a cell suspension can be placed and where the cells themselves have the opportunity to attach to the free surfaces of the material, and the media, with nutrients and other agents, can circulate. Fibrin is commonly used as a matrix and can be modified with peptide sequences from laminin or used to deliver neurotrophic factors with a heparin-binding site Secondly there are the matrices, which are gels, and more specifically hydrogels, involving a network of structural, usually crosslinked, molecules, within a water-based viscous matrix. Guidance scaffolds/polymers based upon poly(-hydroxy acids) demonstrate the ability to stimulate axon growth The principal advantages with the porous scaffold approach are the potential control over the morphology and mechanical characteristics, while the matrix has the very considerable advantage of resembling the extra cellularmatrix within which most cells normally reside.
- 13. Figure: A selectionof approaches for delivering growth factors into peripheral nerve guides. Growth factors can be incorporated into the nerve guide (a) or introduced closer to the lumen with a rod(b) or as growth factor containing microspheres (c). The growth factors may be incorporated into the matrix as non bound (d) or as a Non-covalent controlled release system(e).
- 14. Sequence of events afterimplantation of a fibronectin scaffold in the hemisection lesion of the spinal cord
- 15. Summary Neurotrophic factors playan important, but complicated, role in regenerative therapies. The limited regeneration in the central nervous system (CNS) is primarily due to the different cellular and molecular environment and less to the internal properties of the corresponding neurons. A range of cell and scaffolds implanted into the injured spinal cord reduces astrocytic scarring, promotes tissue sparing, and facilitates axonal regeneration and myelination. Age and gender differences may also need to be taken into account. Tissue engineering therapies for treating traumatic injury (acute/chronic) versus degenerative diseases differ greatly (i.e. what to do and when to do it?). Genetic modification of cells prior to transplantation into the injured brain and spinal cord can increase neuronal survival and enhance the regeneration response. Neural tissue engineering strategies commonly adopt multifactorial strategies both in terms of diversity of therapies (i.e. scaffold and cells and drugs) and timing of interventions (parallel orsequential).
- 16. Thank you forKind attention