Cells as building blocks. Polymer scaffolds as blueprints

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1 David Gold

2 Cells as building blocks GROWTH FACTORS Polymer scaffolds as blueprints

3 Lack of Suitable Methods to Delivery GF in vivo Delivery Requirements: 2 GF simultaneously adjustable rates prolonged release minimal degradation (Bourque et al., 1993; Bostrom et al., 1995; Yu et al., 2002; Chen et al., 2009) (Kasemkijwattana et al., 2000)

4 Develop and test an affinity-based release system for releasing multiple Growth Factors (GF) in vivo.

5 Capitalizing on chemical interactions between the drug and the delivery system to control drug release rates. (Wang and von Recum, 2011)

6 Advantages: Mechanical strength Degradability Our 2-Pronged Attack GF loading device Tissue scaffold Biocompatibility Injectable formulation (Crompton et al., 2007; Costa et al.,2011) Collagen hydrogel

7 DNA Hybridization Factors: ph Salt concentration GC content Strand length Temperature (Clausen-Schaumann et al., 2000; Chalikian et al., 1999) *All strands contain a thiol group at the end of the sequence

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9 1) Confirmation of Chemistry in 2-D Model 2) Study of DNA Melting Temperatures 3) Growth Factor Release

10 Converting inorganic glass to useful thiol

11 Adding hydrogel followed by one strand of DNA Converting inorganic glass to useful thiol

12 Introducing growth factors synthesized with the complementary DNA Adding hydrogel followed by one strand of DNA Converting inorganic glass to useful thiol

13 Tm: 50% duplex Gradual heating (30-80 C) Hypochromism DNA absorbance at 260nm *All strands contain a thiol group at the end of the sequence

14 Low GC High GC

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16 Successful in vitro release results! Novel method of DNA-affinity release Significant variations in release rates Making strides in the developing field of Tissue Engineering

17 Further in vitro testing Other DNA sequences Multiple fluorescently labeled GFs Real GFs In vivo testing Animals followed by humans

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