A mathematical model for the design of fibrin microcapsules with skin cells

Abstract

The use of fibrin in tissue engineering has greatly increased over the last 10 years. The aim of this research was to develop a mathematical model to relate the microcapsule-size and cell-load to growth and oxygen depletion. Keratinocytes were isolated from rat skins and microencapsulated dropping fibrinogen and thrombin solutions. The cell growth was measured with MTT-assay and confirmed using histochemical technique. The oxygen was evaluated using a Clark sensor. It was found that Fick-Monod model explained the cell growth for the first 48 h, but overestimated the same thereafter. It was necessary to add a logistic equation to reach valid results. In relation to the preferred implant alternative, when considering large initial cell loads, the possibility to implant small loads of fast-growing cells arises from the simulations. In relation to the microcapsule size, it was found that a critical diameter could be established from which cell growth velocity is about the same.

Production Process for Stem Cell Based Therapeutic Implants: Expansion of the Production Cell Line and Cultivation of Encapsulated Cells

“…Glucose consumption and growth rates of human mesenchymal stem cells are referred to be (0.23 -1.22) x 10 -7 mg/h/cell [17,18] and 0.33 -0.94 1/d [15,16,[19][20][21][22], respectively. Oxygen consumption rates of (1.22 -3.20) x 10 -8 mg/h/cell are reported for various human cell types [23][24][25][26][27].…”

A BOD monitoring disposable reactor with alginate-entrapped bacteria

“…The bacteria selected were entrapped in calcium alginate beads, using a microencapsulation apparatus with a coaxial superimposed air jet [17,28]. The commencement solution was 1% sodium alginate (Loba Chemie, Food Grade), decreasing at a constant velocity of 1 mL/min on 50 mM of CaCl 2 under gentle stirring [22].…”

“…It has been recognized that inside a bead, oxygen consumption is dependent on bead size [25,27,28]. It is a frequent occurrence in the operation of an immobilized bacteria biosensor, that the limiting factor is oxygen, especially when there is an excess of substrate.…”

Growth factor production from fibrin-encapsulated human keratinocytes

“…Cells were isolated using standard cell and tissue culture procedures, adapted to obtain keratinocytes (Acevedo et al 2009a). Biopsies of human skin were obtained from the foreskins of healthy young donors (\12 years), under informed consent and approval of the surgeon in charge.…”

“…The third principal component (PC3), which Fig. 3 Cell growth was estimated using the method described by Acevedo et al (2009a) to measure growth of keratinocytes into fibrin capsules. a Cell growth, b yield of glucose by lactate only explains 15% of the variability, is an average between lactate and cell growth.…”