3P10: Chronicles 2 Flashcards
(27 cards)
In Cytotoxicity tests – what are the seven things needed to test?
- Cytotoxicity
- Sensitisation
- Haemocompatibility
- Implantation
- Genotoxicity
- Carcinogenicity
- Reproductive and Developmental Toxicity
What are the 4 categories of cytotoxicity?
- Cell death
- Cell damage
- Cell population growth slowed
- Cell metabolism altered
What are the three different cytotoxicity tests for a new material?
- Direct contact with the material
- Diffusion of toxins through a gel layer
-
Exposure of a cell later to a liquid that has been exposed to the material of interest
- Known as “fluid extract”
Note:
- Cells are watched in a culture for a limited period of time, thus results indicative of short term implantation
- Tests also need to relate to end use (short- or long-term)
Give a basic definition of tissue engineering
Instead of replacing defective tissues with manmade devices, try to re-grow healthy tissues by making living implants with active cells.
- Providing cellular prosthesis or replacement parts for the human body
- Providing formed acellular replacement parts capable of inducing regeneration
- Providing tissue or organ-like model systems populated with cells
- Providing vehicles for delivering engineering cells to the organism
- Surfacing non-biological devices
Explain what tissue is and the different types
A tissue is a group of cells that are specialising to carry out a common function
- Epithelial
- Muscle
- Nervous
- Connective
Finish the equation Tissue =, and explain ECM
Tissue = cells + extracellular matrix (ECM)
- The ECM is the structural element of the body
- Collagen is a major component of ECM is most tissues
- Cushions and lubricates cells
Name all the different types of tissues and give their function
Epithelial tissue:
- Skin, linings of tubes
- Used for water-tight barrier functions
Muscle tissue:
- Responsible for the production of force and movement
Nervous tissue:
- Conducts electrical impulses
- Used for signal transmission
Connective tissue:
- Provides structural or mechanical support
- Mostly made up of ECM
- Bones, teeth, ligaments, articular cartilage
What is a scaffold used for?
A scaffold is a 3D construct designed to support cell infiltration, growth and differentiation
- Also enhances new tissue development and guides tissue formation
- All 4 categories of biomaterial have been used for scaffolds
- Mechanical forces can be applied to the bioreactor culture
- Biological small molecules such as growth factors and signalling molecules
What are the different types of cell sources?
- Differentiated cells
- Autologous (self)
- Allogenic (transplant)
- Exogenic (another species)
- Stem cells
- Adult (potentially self)
- Embryonic (use currently limited by ethical issues)
Carticel
Used autologous cell transplantation for cartilage repair
- Used to treat sports injuries
- 2 surgeries: initial cell harvest and implantation
- 2 incisions in the second surgery, one at the cartilage defect, the other at a distance to obtain a periosteal patch
- The time between surgeries is on the order of weeks, the plan where the culture occurs must be kept sterile
Apligraf
A bilayered skin substitute
- The epidermal layer is formed by human keratinocytes
- The dermal layer is composed of human fibroblast (allogenic)
What are the key manufacturing challenges for regenerative tissue engineering?
- Managing regulatory requirements
- Monitoring the long-term health of both tissue and patient
- Delivering and attaching the device in vivo
- High risk manufacturing errors
- Highly complex living systems
- Significant supply chain challenges
- Sterilisation challenges
- Transport limitations
- Obtaining useful quantities of cells can be a challenge
- Process optimisation may be difficult
- Very difficult to characterise and show equivalence
- Cost – Doctors want to minimise their cost, so will use cheapest option available
Advantages and disadvantages of using Autologous cells
- Avoids the challenges of cell/tissue manufacturing, sterilisation and contamination
- Ethically clearer as no stem cells are used
- Transport limitations if not cultured on-site
- Very difficult to scale due to small individual batches, manual preparation
Advantages and disadvantages of using Allogenic cells
- Standard stock, highly controlled, well-characterised, repeatable
- Can delivery large volumes in an economically feasible way
- Transport is still an issue, as this is a centralized facility
- Very complex regulations, as the cells are sourced from a donor
What are the main advantages of controlled drug release?
- Ability to maintain therapeutic drug levels
- Avoids extremely high or dangerously low concentrations
- Improves patient compliance
What are the three types of drug release controlling mechanism?
Diffusion-controlled
- Governed by Fick’s 2nd Law
- Can produce monolithic devices or reservoir devices
Swelling controlled
- Governed by competing diffusivities
- Drug in polymer vs water in polymer
- Water enters polymer pore spaces – swelling – enhanced drug diffusion
Erosion Controlled
- Also governed by competing diffusivities
- Drug in polymer vs water in polymer and polymer hydrolysis reaction rate
- Can be used to erode during tissue growth, or to release a drug
What decides whether erosion occurs in the form of bulk erosion or surface erosion?
- Fast diffusion – Bulk erosion
- Fast hydrolysis – Surface erosion
What is personalised medicine (PM)?
PM is the systematic use of information about each individual patent to select or optimise the patient’s preventative and therapeutic care
- Usually associated with genome-based knowledge for targeted treatment
- PM can also include tissue engineering
What are the challenges of applying PM to therapeutic care/pharmaceuticals?
PM is of great interest in therapeutic care/pharmaceuticals
- Requires enormous changes to current business models
- Limited dosage options
- Patient compliance can be a challenge
Mammaprint
- An individual metastasis risk assessment for breast cancer patients
- 70 critical genes identified and tested for using a microarray chip
Explain the use of PM in IVD test
PM is designed to target the molecular causes of disease, using IVD test to:
- Identify the presence of biomarkers
- Predict response to targeted therapy
Explain what Microelectromechanical systems (MEMS) and microfluidics are
MEMS and microfluidics are fast emerging domains in diagnostics research where nano- and micro-manufacturing is key
- Microfluidics is concerned with handling very low volumes of fluid
- MEMS is used e.g. to make microscopic cantilever array sensors
What are the advantages of nano/micro manufacturing:
- Small size
- High yields of production
- Fast response time
- Increased sensitivity
- Reduced chemical waste
- Fewer human interactions
- Can integrate with a variety of processes
- Facilitates handling of expensive analytes
What is top-down manufacturing?
Involves starting with a large structure and making it smaller
-
Lithography can be used to define patterns on a surface at mm length scales
- UV, X-ray, e-beam lithography
- Nanoimprint lithography
- Ion-beam milling
- Direct write lasers
- Microcontact printing techniques
