Module 3- Organs and Bioprinting

Question 1

Why does there remain a need for partial and whole bladder regeneration?

Answer 1

Pediatric population:
● Abnormal development
● Neurogenic bladder-associated
with spina bifida

Adults:
● Prone to anatomical and functional
loss (surgery, radiation, repeated infections, cancer)

Aging population:
● Muscle under-activity

Question 2

Complex layers of the bladder

Answer 2

Urothelium — an impenetrable barrier that allows for urine containment

Lamina propria — houses the vasculature needed for oxygen and nutrients

Muscle — facilitates urine storage and coordinates the movements needed to expel urine

Question 3

Range of therapeutic treatment for the bladder

Answer 3

• Therapeutic management can range from conservative to minimally invasive to surgery.
• The current standard of care consists of augmenting the bladder with portions of GI tissue
• This approach, however, lacks barrier properties and can lead to…
  ● Tendency to adsorb waste products
  ● Infections
  ● Potential malignancy

Question 4

The regenerative medicine approach for bladders

Answer 4

• The regenerative medicine approach consists of a urinary bladder matrix (UBM) being ECM derived from a porcine urinary bladder.
• The UBM consists of an epithelial membrane and lamina propria

Question 5

UBM increases bladder compliance

Answer 5

• Compliance is defined as the increase in pressure per unit of volume (V/P). Normally the bladder is very compliant and may be filled to large volumes with very little increase in pressure.
• Bladder compliance increases by the same percentage comparing ileum augmentation to UBM.
• UBM does not have associated risks like GI tissue.

Question 6

Autologous cell regenerative approach

Answer 6

36 months did not improve compliance — perhaps because autologous cells were already failing

Question 7

Decellularized scaffolds

Answer 7

Decellularization typically consists of both physical (temperature, force, pressure) and enzymatic steps (immersion or perfusion).

Question 8

Perfusion decellularization

Answer 8

Perfusion decellularization is the primary method for whole-organ decellularization

Question 9

Bladder Acellular Matrix (BAM)

Answer 9

Question 10

Replacing lungs

Answer 10

Question 11

Lung tissue engineering

Answer 11

Design considerations:
1. Extensive surface area
2. Very thin alveolar-capillary
membranes
3. Viscoelastic behavior

Synthetic scaffolds? Not enough control to recapitulate the hierarchy needed.

3D bioprinters? Do not have the resolution to create the gas exchange capillary-alveolar capillary network.

Question 12

Bioengineered lungs video

Answer 12

https://www.youtube.com/watch?v=eyHVlU1dNoE

Question 13

The future of lungs

Answer 13

Question 14

Bioprinting video

Answer 14

https://www.youtube.com/watch?v=SDV0thJFnpQ

Question 15

The complex bioprinting process…

Answer 15

Question 16

A Comparison of Bioprinter Types

Answer 16

Question 17

Examples of human-scale bio-printed tissues.

Answer 17

Question 18

Case Study: Creating Vasculature

Answer 18

• Studies demonstrate that we can use tissue engineering to produce grafts for medium to large vasculature, but creating microvasculature remains elusive.
• Scaffolds were composed of polylactic acid (PLA) and spun into porous nanofiber conduits using electrospinning technology.

Question 19

Microvasculature to engraft organs

Answer 19

Resolution for capillaries remains a problem — we can incorporate angiogenic growth factors such as vascular endothelial growth factor (VEGF) to nurture capillary growth.

Question 20

Can they perfuse? Media can indeed circulate through.

Answer 20

Question 21

Another potential solution to creating vasculature

Answer 21