Lecture 1 - Scaffolds for Tissue Regeneration

Question 1

Tissue Regeneration

Answer 1

• Some tissues can regenerate themselves (skin)
• Some tissues cannot regenerate (heart)
• Most cannot fully regenerate when injured or diseased
• Some can regenerate, but not effectively (length process, large defects, scarring decreases function)

Question 2

Tissue Engineering/Regenerative Strategies

Answer 2

• Cells (stem cells) + scaffold —> “Tissue” —> Implantation (time-consuming, stem cells leave body quickly, hard to control behavior)
• Cells (divided cells) + scaffold —> Implantation
• Cells —> Implantation (hard to control shape/structure without scaffold)
• Scaffold —> Implantation (focus on mechanical properties and not biochemical properties)

Question 3

Scaffolds

Answer 3

• Serve as matrix for cell adhesion to facilitate or regulate cellular processes (growth, migration)
• Maintain shape of defect and prevent distortion of surrounding tissue (ex: blood vessel for blood flow)
• Serve as barrier to surrounding tissue that may impede process of regeneration (ex: bone regeneration)
• Serve as delivery vehicle for cells, growth factors, genes
• Facilitate cell-matrix interactions that are involved with tissue regeneration by providing appropriate sites for cell interaction

Question 4

Scaffolding Materials

Answer 4

• Inorganic Materials (ceramics, bioglass) –> rigid
• Synthetic Polymers (polyesters, polyurethanes) –> biodegradable
• Natural Polymers (collagen, albumin, cellulose (most abundant), chitosan (2nd most abundant)) –> biodegradable

Question 5

Scaffold Types

Answer 5

• Hydrogel (low strength, lots of interactions with tissues, soft)
• Decellularized tissue (natural scaffold from animal models, cells removed)
• Porous scaffold

Question 6

Scaffold Properties

Answer 6

• Match mechanical properties to those of tissue
• Pore size, pore geometry, pore size distribution
• Interconnectivity and porosity (% of void space)
• Cell/scaffold interactions (scaffold surface properties)
• Controlled release of bioactive molecules
• Biodegradation (rate, mechanics vs. time, cytocompatibility)

Question 7

In Vitro Synthesis

Answer 7

• Requires growth of functional tissue in vitro

- Needs scaffolds, cells, regulators such as growth factors combined in bioreactors

Question 8

In Vivo Synthesis

Answer 8

• Highly porous scaffold induces regeneration at wound site where organism would normally respond via repair process (scaffold induced regeneration)
• Scaffolds with well-defined pore microstructure, specific surface area, chemical composition, and degradation rate are keys

Question 9

Role of Scaffold for In Vivo Regeneration

Answer 9

• Physical support for growing tissue
• Regulator affecting cell processes such as migration
• Bioactive scaffold is necessary to induce tissue regeneration (establishes environment that inhibits scar formation) of normally non-regenerative tissues following severe injury

Question 10

Properties for In Vivo Regeneration Scaffolds

Answer 10

• Degradation rate
• Chemical composition
• Pore microstructure (pore size, shape, orientation)
• Scale (size of scaffold enabling internal cell growth)

Question 11

Scaffold Degradation Rate

Answer 11

• Scaffold must initially support cell migration, proliferation and organization, then must degrade without interfering with native tissue growth and remodeling processes
• Approximately equal to time required to synthesize a mature tissue in vivo
• If too slow, dense fibrous (collagen rich) tissue similar to scar forms
• If too fast, soft tissue/scar formation occurs
• Different healing times, must have different degradation rates for regeneration of wounds

Question 12

Scaffold Chemical Composition

Answer 12

• Determines scaffold surface properties
• Surface properties directly affect protein and other biomolecule deposition on surface
• Cell behaviors (attachment, migration, proliferation) are mediated by interactions between cell and biomolecules available on scaffold surface
• Scaffolds must be fabricated from specific materials, in manner leading to expression of chemical environment conducive to cell-scaffold interactions

Question 13

Scaffold Pore Microstructure

Answer 13

• Pore interconnectivity critical for cells to migrate through the construct and to interact with other cells
• Scaffold should have open pores, interconnected for cell migration (cells cannot migrate in closed pore scaffold)

Question 14

Scaffold Porosity

Answer 14

• Must possess porosity > 80-90%
• Pore size: must be large enough to allow cells to fit through and populate scaffold, if too large then surface area too low and insufficient surface area leads to less cell migration
• Pore shape: cells are sensitive to pore shape changes, changes may alter direction of cell migration and orientation within scaffold

Question 15

In Vivo Peripheral Nerve Regeneration

Answer 15

• Tubular conduit necessary for nerve regeneration
• Peripheral nerve cannot regenerate in absence of tubular device connecting two ends of transected nerve stump if gap is too large

Question 16

Tube Chemical Composition

Answer 16

• Tubes fabricated from ECM components (collagen) induce highest quality of peripheral nerve regeneration
• Collagen contains inherently bioactive binding sites for attachment and migration of various cell types
• Collagen tube can be manufactured with wall pore structure displaying range of cell and protein permeability
• Degradation rate of collagen tubes tailored to meet the tissue growth rate

Question 17

Tube Permeability

Answer 17

• Conduit permeability significantly affects quality of peripheral nerve regeneration
• Cell and protein permeable tubes exhibit significantly superior regenerative capacity compared to impermeable tubes

Question 18

Tube Degradation Rate

Answer 18

• Degradable tubes initially induce nerve growth in tube, then degenerate to leave newly formed nerve connection
• Degradable tubes induce higher quality of regeneration compared to non-degradable tubes