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A group of researchers have been trying to generate a degradable scaffold made of polycaprolactone (PCL) for non-load bearing bone substitute. A literature survey indicates that the scaffold for bone tissue engineering should ideally be at least 80% porous with an average pore diameter of 150-220 μm. 4. (a)Discuss the importance of porosity and pore size in tissue engineering scaffolds. (5 marks) (b) The group finally developed a cylindrical scaffold (12 mm in diameter and 10 mm in height) with dry mass of 0.13 gr. A subsequent in-vitro test shows that the scaffold met the minimally required discharge rate of culture media flow of 1.8x103 m/s under physiological pressure (13,300 Pa). Assess the suitability of the developed scaffold in meeting the design criteria of bone tissue engineering. Support your answer with appropriate calculations. (Density of PCL is 1.145 g/cm3, viscosity of culture media is 0.00097 Pa s and blood is 1.5 times the viscosity of the culture media) (20 marks)1.The natural growth model t) - noe kt Whereas: n(t) represents cell quantity [cells] as a Q: Total discharge [m3/s] function of time (t). [days]. no is the initialk: Scaffold intrinsic permeability [m2] cell quantity [cells]; e is Eulers number; and A: Flow cross sectional area [m2] K denotes the cel specific division P Pressure [Pa] at point of index (i). frequency [days ] Whereas: u: Liquid viscosity [Pa s] L: Pressure drop length [m] 2.The logistic growth model: Whereas: n(t) represents cell quantity [cells] as a function of time (t) [days]. M is the carrying capacity for a given set of environmental conditions [cells]; e is Eulers number; IK denotes the cell specific division frequency [days1: and A is a constant defined by Permeability-pore size correlation (Blake-Kozeny equation) M- n 0 150(1- 2)2 no representes the initial cell quantity [cells] d: Average pore diameter [m] e: Porosity (%)s k: permeability [m]function of time (t) [days]. M is the carrying capacity for a given set of environmental conditions [cells]; e is Eulers number; HK denotes the cell specific division frequency [days1: and A is a constant defined by: Permeability-pore size correlation (Blake-Kozeny equation) 0 150(1 c)2 no representes the initial cell quantity [cells] d: Average pore diameter [m] e: Porosity (%)s k: permeability [m2] Porosity calculations PT V1-V Drug delive Whereas: denotes porosity [%]; VP & VT denote the t1/2 In 2/kel pore and total scaffold volumes, respectively; Py and ρΜ denote the total scaffold density and Slab: J-KDCs/-(dM/dt)/A the scaffold material characteristic density, Cylinder: dM/dt-2nhDKCs/ln(ro/ri) respectively [g/cm]. Vi. V2 & Vs represent a Sphere: dM/dt-4TDKCsrori/(ro-ri) non-solvent liquid volumes prior to scaffold submersion (Vi); after scaffold submersion dM/dt (dV/dt)Cs steady state (V2) and cylinder left-overs after dV/dt (A/I) Θ Π removal of the liquid holding scaffold from Π-CN.RT the cylinder (V3) [cm ] R 0.0821 L atm molK1

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(a) Discuss the importance of porosity and pore size in tissue engineering scaffolds.

\Rightarrow Generally, scaffold permeability increases with increasing pore size. Tissue engineering applications commonly encompass the use of three-dimensional scaffolds to provide a suitable micro environment for the incorporation of cells or growth factors to regenerate damaged tissues or organs. The different pore size and porosity measurement methods will also be discussed. Scaffolds with graded porosity have also been studied for their ability to better represent the actual in vivo situation where cells are exposed to layers of different tissues with varying properties.

(b) The cross-sectional area of a cylindrical scaffold is given by -

A = 2\pi r h

where, r = radius of a cylindrical scaffold = 6 x 10-3 m

h = height of a cylindrical scaffold = 10 x 10-3 m

then, we get

A = [(6.28 rad) (6 x 10-3 m) (10 x 10-3 m)]

A = 3.76 x 10-4 m2

(i) The Porosity calculation which will be given by -

\varepsilon = 1 - (\rhoT / \rhoM)

where, \rhoT = total scaffold density = ?

\rhoM = scaffold material characteristic density = 1.145 g/cm3

\varepsilon = porosity = 80% = 0.8

then, we get

(0.8) = 1 - [\rhoT / (1.145 g/cm3)]

[\rhoT / (1.145 g/cm3)] = [1 - (0.8)]

\rhoT = [(0.2) (1.145 g/cm3)]

\rhoT = 0.229 g/cm3

(ii) The permeability-pore size correlation which will be given by -

k = \varepsilon3 d2 / [150 (1 - \varepsilon)2]

where, d = average pore diameter = 220 x 10-6 m

\varepsilon = porosity = 80% = 0.8

then, we get

k = [(0.8)3 (220 x 10-6 m)2] / [(150) (1 - 0.8)3]

k = [(2.47808 x 10-8 m2) / (1.2)]

k = 2.065 x 10-8 m2

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