Tissue engineering Flashcards
*Define the concept of tissue engineering
Tissue engineering is an emerging disciplinary field which applies the principles and methods of engineering and life sciences to the development of viable materials which restore, maintain or improve the function of human tissues.
*Describe and give examples of synthetic and natural biomaterial scaffolds for tissue repair.
Synthetic:
* PGA/PLA, PCL, polyphosphazenes.
* Have the advantage of strength, and ability to control degradation rate, microstructure and permeability
Natural:
* Type I collagen, GAGs, chitosan.
* Advantages: easier for cells to adhere to as they use materials recognised by the body
* Disadvantages: problems with batch to batch variation
Synthetic/natural combinations:
* Synthetic materials with biological properties of ECM (such as RGD attachment)
* Sythesised peptide gels with bioactive properties.
Describe two approaches of tissue engineering.
- ECM or growth factor molecules will be introduced to a wound, tissue or organ. These cause patients own cells to migrate to the wound site, express the desired phenotype and regenerate tissue.
- Patients receive cells that have been harvested previously and incorporated into 3D scaffolds. The entire structure of cells and scaffolding is transplanted into the wound site. This leads to cells replicating and forming new tissue, and the scaffold breaks down.
*Describe clinical applications for tissue engineering and potential future development in this area.
FDA approval has been given for living and non-living skin products, as well as cell based regeneration of articular cartilage (autologous chondrocyte implantation - ACI).
Organs present more complex problems, but due to its regnerative powers the liver holds promise for the future. Experiments have replaced single function of livers, but not yet the entire function.
*Describe scaffold formats used in tissue engineering based on the tissue response sought and the form they take.
The type of tissue response being sought:
- Conducting tissue response and architecture
- Inducing tissue response and architecture
- Blocking tissue response and architecture
Scaffold formats
- Membranes and tubes: to separate cell activity from other cells
- Gels: allows space for maintenance and immunoprotection of non-self cells (protection of foreign cells from immune system)
- Matrices: scaffolds to accurately determine size and shape of an engineered tissue, precisely control function of cells and degrade at rates that optimise tissue formation
*What are the cell sources used in tissue engineering?
Isolated tissue cells, isolated progenitor cells (can be differentiated into different cells), embryonic stem cells (still in research), induced pluripotent stem cells (cells reprogrammed back into stem cells).
Animal cells can also be used, but there are safety concerns as they can be rejected by the immune system.
*Define bioreactors
To grow cells in large quantities, growth chambers called bioreactors are made, equipped with stirrers and sensors. These regulate appropriate amounts of nutrients, gases and waste products.
*Describe the example of cartilage tissue engineering using bioreactors, including requirements, cells and scaffold used, and outcome.
The requirements are to make a 3D scaffold allowing spatially uniform cell attachment and phenotype differentiation/maintenance, and set up an in vitro culture environment for chondrogenesis (cartilage formation).
Cells: Isolated bovine chondrocytes
Scaffold: PGA non-woven mesh, allowing cell differentiation, biodegradation of scaffold.
Bioreactors provide mixing which improves yield, uniformity, increased rates of proliferation and tissue generation.
Outcome (of using a bioreactor compared to static culture): High cell number per construct, greater GAG content and collagen content.
Constructs resemble normal cartilage more, and continue to remodel themselves after implantation to animals.
Describe Apligraf, transcyte, and dermagraft skin products.
Apligraf was the first device to contain living human cells for clinical use. it contains two layers of skin, dermis and epidermis with a scaffold made from bovine collagen.
Cells: fibroblasts and keratinocytes derived from newborn human foreskin, epidermal layer grown on top.
Application: Venous ulcer treatment and potentially burns/diabetic ulcers.
Delivered fresh and has a 5 day shelf life at room temperature.
Transcyte is similar, non-living with a scaffold made from biodegradable polymer.
Cells: fibroblasts from newborn human foreskins.
Application: Treatment of full thickness burns.
Alive, until frozen and shipped for off the shelf use
Dermagraft is similar to transcyte but when frozen the cells are viable at -70C. Used for diabetic foot ulcers.
