Biological Substitutes

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Biological Substitutes Final Project Nerve Tissue Engineering Presented By : Amin Younis Faculty of Biomedical-Engineering Technion

Introduction : Anatomical Background:

Introduction : Anatomical Background The nervous system is a wired communication system of the body. The fundamental component of the human nervous system is the neuron . The various parts can be divided into two parts which differ in their physiology and function: 1)  The Central Nervous System (CNS), 2)  The Peripheral Nervous System (PNS).

Procedure in general:

Procedure in general Isolate cells Expand in culture Living tissue Reconstructed matrix Biochemical interface Structural biomaterials Micro-scale fabrication tools

PNS/CNS Regenerative Ability:

PNS/CNS Regenerative Ability Neurons cannot undergo mitosis. In the PNS nerves can regenerate on their own if injuries are small. Larger injuries must be surgically treated. Spinal cord injury is more complicated, as there are factors in the body that inhibit repair.

PNS/CNS Regenerative Ability:

PNS/CNS Regenerative Ability PNS : Schwann cells, macrophages, and monocytes work together to remove myelin debris, release neurotrophins. CNS : Glial scars inhibit regeneration.

Therapeutic Approaches:

Therapeutic Approaches Peripheral Nerve Regeneration Autologous Nerve Graft Degradable & Non-Degradable Biomaterials

Autologous Nerve Graft:

Autologous Nerve Graft Gold standard – The nerve graft takes tissue from a donor site to use at the injury site. Disadvantages : 1) Loss of tissue/function at donor site. 2) Subjects patients to additional painful and expensive surgeries.

Tissue Eng. Components:

Tissue Eng. Components Two important components in nerve tissue engineering are : A scaffold made up of both natural and synthetic materials and provide structural support for axonal growth. Support cells , which offer a highly preferred substrate for axon migration and release bioactive factors that further enhance nerve migration.

Support Cells:

Support Cells Although autologous cells are excellent source for use in tissue engineering, they are fully differentiated cells and as such they have a decreased ability to proliferate. A pluripotent, highly proliferative cell source obtained from human fetal tissue from which a variety of cell types could be derived became extremely useful in tissue engineering.

Support Cells:

Support Cells Using stem cells in nerve degeneration : To grow in a laboratory dish differentiated cells that are suitable for implantation into a patient by starting with undifferentiated neural cells. Finding growth hormones and other “trophic factors” - that help cells survive and grow. Which finally stimulates repair mechanisms


Scaffolds The nerve graft must be integrated into the surrounding tissues and must guide the nerve fibers between two ends of damaged nerve. To prevent fibrous tissue from invading the nerve gap. To be stable as long as the regenerating nerve fibers are not mature enough. To disappear rather than being removed, to avoid the risk of injuring the repaired nerve. Reqiurments :

Scaffolds - Nerve Guidance Channels -:

Scaffolds - Nerve Guidance Channels - Non-biodegradable Artificial Nerve Grafts Biodegradable Artificial Nerve Grafts

Non-Biodegradable :

Non-Biodegradable Silicon tubing was used as a synthetic material for nerve grafts. Much fundamental insight into nerve regeneration has come from the use of this model system. Inert silicone tubes can be used to bridge short gaps with some success.

Biodegradable :

Biodegradable A graft that degrades slowly enough to maintain a stable support structure for the entire regeneration process but will not remain in the body much longer than needed.



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- As the scaffold degraded, the neural cells differentiated into neurons and insulating (glial) cells. Biodegradable


Biomaterials Natural Glycosaminoglycans Laminin Collagen Fibronectin Hyaluronic acid Fibrin gels Agarose Synthetic PGA (glycolic acid) PLA (lactic acid) PLGA (lactic-co-glycolic acid) PEG (ethylene glycol) Poly (urethane) Poly (3-hydroxybutyrate)

Requirements of materials used as a nerve guide:

Requirements of materials used as a nerve guide

Regeneration obstacles:

Regeneration obstacles Cell body response. Degeneration of the distal stump. Swelling of the proximal stump. Possible gap between nerve stumps

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