Polynucleotide Biohybrids

Polynucleotides can be incorporated into hydrogel networks mainly through two different strategies. The first uses dual-functionalized ssDNA, such as polynucleotides with amino groups on both ends, as permanent linker groups to induce covalent cross-linking of functionalized polymer backbones. In the second approach, duplex DNA formed by DNA hybridization serves as the noncovalent cross-linker for the hydrogels [93]. 

FIGURE 5.28 Target ssDNA-induced volume change of hairpin DNA (top) and DNA without secondary structure cross-linked polymer hydrogels. Source Peng et al. [93]. Reproduced with permission from the Royal Society of Chemistry. 

2 Noncovalent Cross-Linking by DNA Hybridization Nagahara and Matsuda [97] used the second approach to form a polyacryl-amide/DNA hybrid hydrogel. They grafted complementary ssDNA onto polyacrylamide. Upon mixing, cross-linking based on duplex formation due to DNA hybridization occurred. 

Alternatively, polyacrylamide chains were functionalized with two different noncomplementary ssDNAs. Cross-linking was then achieved with a third ssDNA ( cross-linker ) that had terminal complementary sequences to the 

The reversible nature of DNA hybridization in response to an external stimulus causes this type of DNA-polymer hydrogels to have special properties, such as sol-gel phase transition and responsive releasing capability [93]. Thus, potential applications of these materials as label-free DNA sensing device or for controlled drug delivery have been discussed. Just a small portion of DNA is needed to achieve hydrogel responsiveness. 

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This chapter will introduce polymer systems containing either naturally occurring maaomolecules (polysaccharides, proteins, DNA) or their subunits (bioanalogous molecules, amino acids, short peptides and peptide derivatives, polypeptides, polynucleotides), respectively. The natural building blocks can be connected by covalent bonds or by self-assembly and either can be used alone (see, e.g.. Section 5.4) or in combination with synthetic polymer units (biohybrids). Alternatively the building block itself may be a hybrid of a natural and synthetic molecule (bioconjugate cf. Section 3.5), as, for instance, a PEG-peptide conjugate. 

In the following we will briefly describe some selected examples of biohybrid structures and networks consisting of synthetic organic polymers and polynucleotides, polypeptides/proteins, and/or polysaccharides with focus on biomedical applications. In order to provide multifunctional biohybrid materials with the optimal combination of mechanical, biological, and stmctural properties for particular purposes, different design aspects must be considered. 

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