Module 3- Biomaterials and Tissue Engineering Flashcards
What does the need for tissue replacement look like? (graph)
Demand for tissue engineering and projected cost
- There is great demand for tissue engineering, with a projected US market of around 33 billion USD in the coming decade.
- There are now over 20 FDA-approved commercial products, including skin and orthopedic replacements.
What is the goal of tissue engineering?
- For tissue-engineered products to be implanted and regenerate function of the tissue or organ
Structural and metabolic tissue-engineered products
Structural:
- Skin, cartilage, bone
- Myocardial patch, heart valves
- Veins and arteries
- Scaffolds and whole organs (bladder, heart)
Metabolic:
- Bioartificial liver, kidney, pancreas
- Immunoisolation device to deliver cell and gene therapy
In vitro generation and in vivo regeneration
After an in vitro generation of the tissue, implantation should lead to an in vivo regeneration of the lost/failing function
The biomaterial and tissue engineering toolbox
Scaffold (conductive)
● Provide structural support, shape, and place for cell attachment and growth
● Biocompatible
● Sometimes biodegradable
Signaling molecules (inductive)
● Signal cells with instructions
● Proteins and growth factors
● Mechanical stimulation
Cells (productive)
● Living part of tissue
● Provides function
● Produces proteins
● Gives tissue reparative
properties
Scaffold/matrix, soluble factors, and cells diagram
Challenges to biomaterial and tissue engineering
- Biological structures and functions are complex and require dynamic interactions between cells, scaffolds, and soluble molecules.
- Some ongoing difficulties in the field include…
1. Biomaterial rejection
2. Density and variety of cells
3. Cost of tissue and organ development
4. Vascularization
Timeline of tissue engineering
Earmouse
● Created in 1997 by tissue engineers at MIT
● Biodegradable ear-shaped scaffold
● Seeded with cow chondrocytes
● Immunosuppressed mouse strain
Mass protests erupted against genetic engineering — even though no form of genetic manipulation was performed.
The world’s first synthetic, tissue-engineered organ transplant
- In Sweden in 2011, a cancer patient needed a new trachea to survive
- Although the transplant was a low hanging fruit and the trachea was purely mechanical, it was an important first step for the field
Artificial trachea video
https://www.youtube.com/watch?v=3jv_Z28mFXY
What is the current status of the artificial trachea?
- There have been 15 additional trachea transplants — all of which appeared to be a short-term fix.
- Research has considered different biomaterials for better long-term success, although the misconduct cases have halted some of this progress.
- Are surgeries examples of successful tissue engineering that utilize the special abilities of stem cells or an elaborate temporary fix that is destined to fail?
Design criteria for tissue engineering
What type of tissues and functions are being replaced?
- Structural v. Functional
Is vascularization required?
- Cartilage v. Cardiac repair
Ex vivo or in situ or paracorporeal?
- Prefabricated implant v. Stem cell infusion v. Bio-artificial liver
Cell types, scaffolds, soluble factors?
- Cell sources, Synthetic v. Natural, and Bound v. Free
Diabetic ulcers
- Diabetic ulcers occur in 15% of patients with diabetes.
- The condition precedes 84% of all diabetes related leg amputations.
Traditional treatments for diabetic ulcers
Maggot therapy for ulcers that become infected with multi-drug resistant bacteria
Living skin equivalents for diabetic ulcers
Two versions Apligraf© (organogenesis) and Dermagraft© (ATS) have been FDA approved and utilized by over 60,000 patients
Apligraf vs. Human skin
Healing process of Apligraf
The future of wound healing
Cartilage structure
Cartilage has a complex 3 dimensional shape, but also has low cell density and is avascular
Joint cartilage engineering
Steps of joint cartilage engineering
1) Initial arthroscopy with evaluation of the injured cartilage and harvest of a full-thickness cartilage biopsy
2) Biopsy sent to the cell culture laboratory
3) Cartilage is enzymatically digested
4) Expansion of the chondrocytes in a monolayer culture or about four weeks
5) Cells are seeded onto the scaffold a few days before implantation
6) Engineered implant sent back to the surgeon
7) Definitive surgery with debridement of the injured cartilage followed by implantation of the MACI-implant, which is trimmed to fit the defect size and glued with a thin layer of fibrin glue
Biopsy and implantation
