3P10: Chronicles 2 Flashcards
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
Explain UV & Nanoimprint lithography as well as microcontact printing
UV lithography
- Use a UV source and mask to produce a positive photo resist on a Si substrate
- Develop away the pattern
- Deposit metal on the pattern
- Life off the “ink layer”
Nanoimprint lithography
- Use a mould to make a pattern in the resist layer
- Remove the mould
- Use a reactive ion etching to transfer the pattern
Microcontact printing
- Use ion beam milling or lithography to apply to the surface
- Mould the pattern with PDMS
- “Ink” the PDMS
- Stamp the pattern onto the sample
Explain bottom-up manufacturing
Bottom-up manufacturing starts at the atomic/molecular level and builds up
- Design molecular building blocks which spontaneously assemble into the desired structures
- E.g. using H-bonds, dispersion forces etc.
- Allows scaffolds and drug delivery materials with tuned nanostructures to built
To what does the term “professional services” refer in relation to medical device manufacturing. Postulate why this may be a key growth area in the medical technology sector.
- Refers to advisors and consultants hired to help firms regulate, classify and register new medical devices.
- As devices become more diverse then regulations will have to evolve accordingly. This increases demand for such services
- Highly likely that services of lawyers and ethical advisors will become increasingly important, as new technologies emerge in areas such as genetic modification and stem cell adaptation and spark moral and ethical debates
