Thirdgeneration biomedical materials

1
Third-generation biomedical materials

• Hench and Polak (2002). Science 295, p. 1014

2
First generation

• First were off-the-shelf (1960s and 70s)
• Readily available
• Minimize toxic response in host and immune
  response
• 1980 50 implanted devices using 40 different
  materials
• 2-3 million implanted annually in US
• Millions had life span enhanced 5-25 years

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First generation example

• Artificial heart valve being implanted

4
Second generation

• Emphasis switched from inert tissue response to
  producing bioactive components that elicited a
  reaction in the physiological environment

5
Second generation example

• For bone implants, creating a high-surface area
  silica gel which was equivalent to the inorganic
  mineral phase of bone. Osteoblasts (the cells
  that make bone) colonized the surface and formed
  new bone that had a mechanically strong bond to
  the implant surface.

6
Second generation example

• Development of biomaterials that are reabsorbed,
  so that the foreign material is replaced by
  regenerating tissues.
• Biodegradable sutures are now routine.
• http//www.reactivereports.com/25/25_4.html
  (Sutures that tighten themselves)

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Second generation limitations

• Survival analyses of some biomaterials such as
  skeletal prostheses and artificial heart values
  show that ½ fail with 10 to 25 years and new
  surgery needed.
• 20 years of research failed to reduce failure
  rates.
• Problem is that man-made biomaterials cannot
  respond to changes in physiological loads.

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Third-Generation

• Designed to stimulate specific cellular responses
  at the molecular level.
• Resorbable polymers (scaffolds) are being made
  bioactive release chemicals as dissolve.
• Elicit specific interactions with cell surface
  receptors and thus direct cell proliferation,
  differentiation and extracellular matrix
  production and organization.

9
Third-Generation example

• Particulate of bioactive glass is used to fill a
  bone defect.
• Rapid regeneration of bone that matches
  architecture and mechanical properties of bone at
  the site of repair.
• How is this accomplished?

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Third-Generation example

• Rapid repair of bone requires differentiation as
  well as proliferation of osteoblasts
• Synchronized sequence of genes must be activated
  so osteoblasts undergo cell division and
  synthesize extracelluar matrix

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Third-Generation example

• Dissoultion products of bioactive glass initiate
  upregulation of several families of genes within
  48 hours.
• Genes express several proteins that influence all
  aspects of differentiation and proliferation of
  osteoblasts.

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Third-Generation where now?

• Further development of molecular tailoring of
  resorbable polymers for specific cellular
  responses.
• Design new generation of gene-activating
  biomaterials tailored for specific patients and
  disease states.
• Possibility of bioactive stimuli to activate
  genes in a preventative treatment to maintain
  health of tissues as they age.