University of Trento Master of Molecular and Cellular

Biotechnology Tissue Engineering and Regenerative

Medicine Ahmed Ali Matriculation . No 161603

Drug release in Tissue Engineering

Scaffold categorized as Cell delivery scaffold Drug delivery scaffold

Common Parameters for both : 1. 3D architecture desired shape ,volume , mechanical strength 2. Highly porous structure with interconnectivity seeding cells ,Nutrients Diff ,Waste p. 3.Chemical composition ,for degradation pds. Biocompatable ,minim inflammatory response 4. Interface Adherance ,Surface , support adhesion ,proliferation ,cell-cell , migration. 5. Biodegradable ,acurrate degradation rate 6. Mimic native ECM

Specific parameters for drug release scaffold

1. Loading Capacity dgs mixed with scaffold ,scaffold show max loading capacity in

sustained release manner

2. Drug distribution homogenous

3. Binding Affinity low to allow release but not too low

4. Stability physic dimension , chemical structure ,during the prolonged treatment

What are types of Scaffold used ?

Implantation Injection

Scope vision using injectable hydrogel scaffold in drug release

Advantages over Implantation : 1. Network of polymers chain ,Synth ,natural

2.Hydrophilic 99.9% H2O

3. Flexibility , biocompatibility

4. Enable sustained drug release upon swelling ,control release behavior from gel

5. No longer ( prefabrication , minimum invasive surgical , implanted drug depot problems ,doctor visit )

6. Safety ,Efficacy

7. known as Smart Gel ?

In situ gel preparations( Hydrogel inject . Scaffold) in Drug release

Types according to Stimulant ( solution( vitro )to Gel ( vivo ) )

Once swelling ,once being Gel ,sustained release begin

Stimulant

chemical PH Osmotically

ionic cross linking enzymatic cross linking Photo polymerization

Smart, why ?

1 . In Temperature : Room 20-25 °C liquid ,once in vivo with B . fluids 37 ,swell,solidify .

Advantage : wide use ,simple , no need chemical stimulant .

Best Smart biomaterial sensitive :

Natural : Cellulose Deriv ,Chitosan,

Carrageenans ( Red marine Algae )

Synthet : poloxamers , Xyloglucan,

Smart, why ?

2.PH

2.1. Polymers containing acidic F . Group ,swelling in Environmental PH high .

2.2. Polymers containing Basic F . Group , swelling in PH low

Best smart bio-metrial sensitive :

CAP ( cellulose acetate phthalate ) , AEA ( Poly vinyl acetyl diethyl amino acetate ) , PMMA (Poly methyl methacrylate )

Osmotically induced :

Gel Formation depend on presence osmotic gradient across the surface of Hydrogel :

Ex . Presence of mono,di ,valent cations Na , Ca , Mg ,they naturally found in Eye tear fluids .

Best polymers used :

Gelrite ( deacetylated gellan gum ) ,Hyaluronic acid ,Alginate

In Market :

Hydrogel Gelrite , sustained release Timolol , Treat ,Glucoma

Chemical induced by Photo –polymerization

Polymers contacting Acrylate F . Group + photo initiator ( eosin dye ) + UV light source ,creation free radicles ,form polymerization ,gel , release drug from the biodegradable P - P hydrogel in prolonged period of time .

Synthetic Polym ,more popular choice in Hydrogel ? High biodegradable property.

Drug release in injectable porous microsphere scaffold model

Porous polypropylene Fumarate PPF combine with PLGA (poly lactide co glycolide ) microsphere scaffold.

Adv : show sustained release of drug 28 days more than PLGA alone.

Some Drug release scaffold models

1. PLGA porous microsphere scaffold and gatifloxacin

2. PLGA porous microsphere scaffold and doxurobucin

3 . In bone regeneration :bone marrow stem cells + Dexamethasone ( Ster. Anti inflammatory ) loaded in bulk of PLGA scaffold implantation, Dexam has role in inducing differentiation of St. cells to osteoblasts and chondrocytes

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