Tissue engineering - Add? Flashcards
Regenerative Medicine
What is regenerative medicine?
The process of creating living, functional tissues to replace or regenerate human cells, tissues or organs to restore or establish normal function
An umbrella term which contains tissue engineering
What are scaffolds used for?
Scaffolds have been attempted using a variety of biomaterials and technique
Aligned scaffolding has higher cell viability than nonwoven scaffolding Each class of biomaterials have cons, so composites are used – show promise but still may have problems with biocompatibility and biodegradability
Ceramics in polymer-based scaffolds
Combination synthetic and natural polymer scaffolds to enhance biological capacity
Decellularized matrices are tissues that have come from a donor or cadaver in which the cells have been lysed to leave the extracellular components undamaged, resulting in a natural extracellular matrix that can be used as a scaffold. The provide durability, enhanced integration, biocompatibility and avoid allosensitization
Why must biocompatibility be considered in tissue engineering?
cells must adhere, function normally, proliferate and have no immune or inflammatory response
Why must biodegradability be considered in tissue engineering?
scaffolds are not permanent implants, as body cells should replace the implanted scaffold, but it should be able to stay for an extended period of time before cell growth is complete. By-products of biodegradation should be non-toxic and able to be excreted
Why must mechanical properties be considered in tissue engineering?
strong enough for surgical manipulation, have sufficient mechanical integrity to complete re-modelling, match properties of anatomical site to which it is being implanted
Why must scaffold architecture be considered in tissue engineering?
needs an interconnected pore structure with high porosity to enable cellular penetration, diffuse nutrients to cells and matrix, remove waste products of cells and scaffold degradation, and allow vascularization
Why must manufacturing technology be considered in tissue engineering?
cost effective, possible to scale-up, consider how the clinician will receive and use the product (e.g. does it require patients own cells?)
Why must biocompatibility be considered in tissue engineering?
Natural polymers – biologically active, promote good cell adhesion and growth, biodegradable, difficult to fabricate, poor mechanical properties
Synthetic polymers – can be fabricated and tailored, control of degradation, risk of rejection (lack of bioactivity), degradation of many polymers may result in cell necrosis
Ceramics – very compatible with native mineral bone (high mechanical stiffness, low elasticity, hard brittle surface), enhances osteoblast differentiation and proliferation, difficult to shape (brittle), unable to sustain mechanical loading needed for remodeling, degradation is difficult to control
How are stem cells used in tissue engineering?
Can be autologous (from patient), allogenic (human donor), xenogeneic (animal)
Embryonic stem cells are ethically questionable (derived from embryo 5-days post fertilisation in blastocyst stage)
Adult mesenchymal stem cells are the most commonly used. From bone-marrow and proven to differentiate in cells for treating bone, cartilage, nervous, muscle, cardiovascular, blood and GI disease. These do however have low numbers, and difficult in vitro expansion without differentiation (Usually already partially differentiated)
Allogenic cells sources with low antigenicity (e.g. human foreskin fibroblasts as used in wound healing grafts (GINTUIT, Apligraft) allow off-the-shelf tissues to be mass produced with reduced risk of adverse immune reaction
What are induced pluripotent stem cells?
similar to embryonic stem cells but easier to generate and with no ethical issues. The issue with this is tumourigenity.
When cultured they are capable of unlimited self-renewal and reproduction of all adult cell types in the course of their differentiation
Can be obtained by reprogramming animal and human differentiated cells, gaining the same pluripotency as embryonic stem cells. Supported by a complex system of signalling molecules and gene network that is specific for pluripotent cells
Spontaneous and direct differentiations are both associated with changes in the expression pattern and massive epigenetic transformations. This leads to transcriptome and epigenome adjustment into a distinct cell type
What are human iPSCs?
human induced pluripotent stem cells
Overcomes legal, ethical and moral barriers associated with embryonic or epiblast (?) stem cells, but induction of pluripotency includes risk of; mutation, retention of somatic epigenetic memory, potential for immunogenicity (especially if mutated), and altered functional characteristics of differentiated phenotypes
It is very difficult to direct differentiation of iPSCs to a specific cell type, particularly on large scales (even stirring speed, change of light or change of temperature can trigger differentiation). Within batches and between batches they can differentiate differently
Most iPSC clinical trials have been suspended as they have been implanted and did not function as needed, and due to tumorigenicity and immune response seen in mice
Behaviour of iPSC populations cultured in vitro are dependent on genetic variations present in the derived source cell line and the culture environment in which they are sustained
what are the levels of tissue engineering?
Level 1 – flat tissue: layers of cartilage, muscle, skin (easy)
Level 2 – tubular: blood vessels, esophagus, fallopian tubes, intestine, trachea, ureter, urethra
Level 3 – hollow non-tubular: bladder, stomach, vagina (mixed success)
Level 4 – solid organs: heart, kidney, liver, lung (very limited success)
