tissue engineering and the brain - lehigh universityinbios21/pdf/fall2011/perry_09212011.pdf ·...
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Tissue Engineering and the Brain
Susan Perry
Bioengineering Program Lehigh University
“...all the most acute, most powerful, and most deadly diseases, and those which are most difficult to be understood by the inexperienced, fall upon the brain..”
Hippocrates
Outline
• Introduction and Review of the components
• Target areas for Neuroengineering Strategies
• Neuroengineering Strategies: new thinking, creative design and innovative technologies
Axon Regeneration and Innervation Cell Replacement Drug Delivery Electrical Stimulation
The Nervous System:
Peripheral Central
Nervous System (PNS) Nervous System (CNS)
Autonomic NS Somatic NS Spinal Cord Brain
Sympathetic NS Parasympathetic NS
Forebrain Midbrain Hindbrain
Telencephelon Diencephalon Mesencephalon Metencephalon Myelencephalon
Specific Neuroanatomical Areas of the Brain
Enteric
Spinal and Cranial Nerves
• Basic Research has provided us with an incredible breadth of knowledge – Development – Anatomy – Cell types – Organization – Connections – Stimulation – Synaptic transmission – Gene Regulation – Control systems – Malfunctions and insults
Insults to the Nervous System • PNS nerve problems
– Neuropathies, injury • Spinal Cord Injury
– Incomplete or complete • Traumatic Brain Injury
– Loss of cognitive function, loss of motor control, alteration in behavior
• Neurodegenerative Diseases – Alzheimer's disease, Parkinson’s disease, etc.
• Sensory disorders – Deafness, hearing impairment – Vision Loss – Loss of Tactile sensation due to nerve injury
Spinal Cord Injuries
•Approximately 12,000 new cases/year, with an estimated 260,000 living with SCI in US.
•Almost 81% of those injured are male
•Estimated costs:
Traumatic Brain Injury • Nondegenerative insult to brain from external
mechanical force (Compressive, tensile and shear deformations)
• Estimated that 1.4 million people sustain TBI’s each year
• Approximately 5.3 million in US live with disability from TBI
• 2o injury by neurochemical mediators
increases cell death
Rehman et al, (2008).
Neurodegenerative Diseases and Disorders (just to name a few)
Parkinson’s Disease – 1.5 million people, degeneration of dopaminergic neurons
Alzheimer’s Disease -5 million people, brain-wide neuronal loss
Huntington’s Disease-1 in 10,000,
multiple neuronal sets affected
Epilepsy-3 million people, loss of
neurons in cerebral cortex, or
neuronal damage
Multiple Sclerosis-300,000 cases in US,
degeneration of oligodendrocytes
Sensory System Disorders
• Affecting vision, hearing, balance, position and other senses perceiving environmental stimuli
Current Treatment Strategies
Treatment focused, primarily, on limiting damage and slowing degeneration.
Restoration of function not always possible
Neuroscience + Engineering = The Next Wave
Neuroengineering Treatment Strategies
Technological interventions that provide solutions to neurological disease and other insults to the nervous system
Therapies, such as transplantation of stem cells or genetically engineered cells, which will correct the mechanisms of disease
Neuroengineering Strategies
• Combinatorial Approach using neuroscience, bioengineering, materials science, developmental biology, computer science, nanotechnology
• 4 Main Areas of Attack – Axon guidance devices – Drug delivery – Cell replacement – Electrical stimulation
Axon Guidance Devices • Strategy is to create physical or chemical pathways for
regenerating axons or for innervation of new tissue
biomed.brown.eduu
• Entubulation techniques – Synthetic or biological materials
– Well-controlled bridge environment between 2 stumps
• Bioactive scaffolds
• Carbon nanotubes, in combination with biological materials
• PNS repair has been more successful than CNS repair
• Upregulation of regeneration-associated genes and presence of Schwann cells
• Nerve Growth Channels – Barrier to scar tissue
– Can be loaded with cells, coated with ECM proteins or growth factors to facilitate regeneration
– Can be designed to include electrical stimulation
– Can be designed to incorporate biodegradable drug delivery
– Where distal stump is present, over 5mm growth
Axon Regeneration in the CNS • Environment is largely inhibitory and non-permissive
(scar tissue) • Oligodendrocytes, reactive astrocytes, myelin-
associated glycoproteins, CSPG
• Experimental Strategies: – Biological and Synthetic Bridges – incorporate physical
guidance cues or controlled environment
– Optimal biomolecular surface coatings, co-transplanted cells, mechanisms for sustained release of therapeutic agents • Drugs that decrease scar tissue formation
• Neurotrophic factors for guidance and trophic support
Drug Delivery Systems for Targeted Delivery and Controlled Release
• Scaffold-Based Delivery – Degradation/Diffusion Based Systems
– Affinity-Based Systems (non-covalent)
– Immobilized Drug Delivery (covalent)
• Chemical Delivery Systems – Lipisomes, nanoparticles, microspheres
• Electrically controlled delivery – coating of neural electrodes
– microchips
Drug Delivery: Implantable pumps
• Delivery of pain relief
• Sustained or timed release of medications to correct
neurosecretion malfunctions, Parkinson’s, epilepsy, etc
Cell Population Recovery • Advances in stem cell technologies mean most neuronal and
neural populations needed for repair can be derived from stem cells
• Functional consequences of using stem cells in vivo are currently unpredictable
• Goal: to produce specific, functionally
differentiated populations – sufficient quantities
– To maintain the differentiated states,
in vitro, for transplanting, or in the in vivo
environment, as replacement cells
Hope for Parkinson’s Disease: Cell Population Recovery
• “Naked” cell/tissue transplantation- – good in theory, immunogenicity issues
• More promising:
– Cell/tissue encapsulation (into microparticles)
and transplantation to substantia nigra
– Recruiting native progenitor cells (stem cells in SVZ) into substantia nigra and inducing desired phenotype
Hope for Parkinson’s Disease: Electrical
Stimulation
http://www.parkinson.org/Parkinson-s-Disease/Treatment/Surgical-Treatment-Options/Deep-Brain-Stimulation.aspx
Electrical impulses produced by the neurostimulator interfere with and block the electrical signals that cause PD symptoms.
Electrical Stimulation, con’t
• Neuromodulation approach-coupling electrical sensing and stimulation capabilities – “closed loop” systems
• MEAs – Microelectrode Arrays – Cochlear Implants
– Brain/computer interfaces
– Vision Restoration
http://www.kevinwarwick.com/the_neural_interface.htm
The Process of Vision Light waves enter and are focused on the retina Specialized photoreceptor cells in the retinal layer absorb the light, beginning a biochemical cascade
Result:
Chemical signals are converted into electrical signals, carried by the optic nerves, to the brain for processing.
Problems:
Abnormalities, injury, diseases of retina resulting in partial or complete loss of vision
What hope is there for restoring vision?
Artificial Silicon Retina Argus II 5000 microscopic solar cells video camera/micro-
Powered by incident light chip converts patterns
Requires some intact retina into electrical pulses
sent to retinal implant
BrainPort Vision Technology • Utilizes Cross-Sensory input: using one type of sensory
stimulation to convey info about a different type of sensory input – Brain learns to interpret information as if it were being sent through
traditional channels
• Patterns of light from a video camera converted into electrical pulses on the tongue that represent the pattern Nerve fibers normally responsible for touch sensation are stimulated
Key Points to Remember – Neuroengineering requires a multidisciplinary
approach – developmental biology, engineering, materials science,
neuroscience, molecular biology, computer science
– 4 main areas of research – Axon guidance devices for regeneration and regrowth of
axons – Cell population recovery through stem cell technology – Drug delivery methods for enhancement of axonal growth,
cell survival and proliferation, regulation of important cell functions, and for pain management
– Electrical Stimulation to tune excitable cells
– Most therapies of the future for treatment and cure of neurological diseases and nervous system injury will likely be combinatorial