# Biodegradable Polymeric Architectures via Reversible Deactivation Radical Polymerizations
## 2 Biodegradable Polymeric Architectures
### Polymeric Architectures Based on Biodegradable Synthetic or Natural Precursors  
Biodegradable architectures can also be achieved by grafting polymer chains onto the biodegradable precursors. The degradation of biodegradable precursors will consequently disintegrate the as-prepared architectures. These precursors can be synthetic biocompatible and biodegradable films, such as poly(3-hydroxybutyrate-_co_-3-hydroxyhexanoate) (P(HB-_co_-HHx)) (Figure 12a) [117]. Cellulose is a natural polysaccharide consisting of a linear chain of several hundreds to over ten thousand linked D-glucose units. It is the major constituent of paper, paperboard, and card stock and of textiles made from cotton, linen, and other plant fibers. Its high hydrophilicity is right due to the multi-hydroxy groups from the glucose units. These hydroxy groups not only make the cellulose chains holding firmly together side-by-side and forming microfibrils with high tensile strength, they can also be used to make soluble and functionalized cellulose. The biodegradable cellulose would be a good precursor for generation of biodegradable architectures. A few groups have explored the possibility of modifying cellulose. [PERSON] et al. successfully modified the cellulose using ATRP via \"graft from\" methodology. They first attached 2-bromoisobutylryl bromide on the cellulose surface through the condensation reaction with the surface hydroxyl group, followed by the ATRP reaction to create an amphiphilic block copolymer layer on it [118]. Using the same methodology, [PERSON] and coworkers successfully attached different RAFT agents through the surface hydroxyl groups for direct grafting an amphiphilic copolymer, poly(ethylene glycol)-_b_-poly(L-lactic acid), from the cellulose surface. The biodegradable poly(L-lactic acid) block further facilitates the biodegradability of the so-prepared architecture [119]. One advantage of RAFT polymerization is the versatile initiation methods. In addition to the commonly used thermal initiation, other ionizing radiation sources, such as \(\gamma\)-ray, ultraviolet, microwave and X-ray radiation, have also been used to initiate RAFT controlled polymerizations [20; 120; 121; 122]. [PERSON] and coworkers used both thermal and \(\gamma\)-ray initiations and RAFT polymerization to modify cellulose with styrene and sodium 4-styrenesulfonate polymeric brushes using \"graft from\" methodology [123; 124]. Cellulose fiber was also modified with biodegradable polyesters by the aid of host-guest inclusion complexation between \(\beta\)-cyclodextrinrin and adamantine motifs [125]. Figure 12: (**a**) Synthesis of the gradient copolymers; (**b**) Synthesis of the block copolymers; (**c**) Synthesis of thermo-responsive surfaces. Copyright 2010, Wiley-VCH; (**d**) Synthesis of branched poly (\(N\)-(2-hydroxypropyl) methacrylate) (PHPMA) and the subsequent conjugation with protein. Copyright 2009, American Chemical Society. \"Glycopolymers\", particularly the multivalent ones have attracted tremendous attention due to the potential applications in biomedicine and biomaterials. [PERSON] and coworkers synthesized a four-armed star glycopolymer composed of block copolymer arms bearing lactone end groups. These star polymers could self-assemble onto nanoparticles that carry the lactose groups on their surface, allowing for the further complexing with lectins to achieve biodegradable biohybrids [126]. Glycopolymers were synthesized by [PERSON] and coworkers using RAFT polymerization and thio-ene click chemistry to fabricate glucose surface tethered glycol micelles for further complexation with concanavalin A, a mannose and glucose specific lectin. These biodegradable and biocompatible glycol micelles could be utilized as potential drug carriers [127]. [PERSON] et al. also prepared large spherical micelles in aqueous solution, using star-shaped polypeptide/glycopolymer biohybrids composed of poly(\(\gamma\)-benzyl l-glutamate) and poly(D-glucuronadioethyl methacrylate) prepared via ROP and ATRP.