## 4 Potential Applications of Peptide-Synthetic Polymer Hybrids
### Crosslinked Hydrogels and Scaffolds for Tissue Engineering  
Hidrogels are three-dimensional networks crosslinked with hydrophilic polymers. They possess biocompatibility, the possibility to store high water content and can be tuned chemically and physically exhibiting good mechanical properties. Due to these unique properties, hydrogels have great potential in the development of useful biomaterials, principally for biological and biomedical applications [96]. In addition, peptides, proteins, poly(amino acid)s, and hybrid macromolecules spontaneously undergo biorecognition-driven self assembly into hydrogel structures. Developments that may be expected in the near future include: design of hydrogels with multiple functions, hydrogels sensitive to stimuli, hydrogels with programmable responses, and hydrogels translating substrate recognition into mechanical action [97]. Peptide-synthetic polymer hybrids are also gaining attention in three dimensional cell culture applications taking into account, for example, that reverse thermal gelling polymer aqueous solutions undergoes sol-to-gel transition as the temperature increases. Therefore, these systems can be used for the formation of drug or cell encapsulating 3D hydrogel matrix by mixing drugs or cells in a low viscous sol state, followed by increasing temperature. Growth factors can be also simply incorporated, and by injecting the polymer aqueous solution, it can easily take the shape of the cavity or the disease site, avoiding the use of surgical procedures. Related to the last studies performed on peptide-synthetic polymer hybrid hydrogels usable as injectable scaffolds, two recent works developed by [PERSON] _et al._[98, 99] merit attention. In this way, a thermogelling system, in which the solution to gel transformation occurred from 10 \({}^{\circ}\)C to 37 \({}^{\circ}\)C, was used as an injectable _in situ_ gelling system into the subcutaneous layer of rats. The system consisted on poly(ethylene glycol)-poly(L-alanine-_co_-L-phenylalanine) grafted chitosan (CS-g-(PAF-PEG)) where specifically phenylalanine units were incorporated in the peptide segment to strengthen its hydrophobicity. This polymer was able to form micelles with diameters ranging from 10 to 50 nm at low temperatures and large aggregates ranging from hundreds to thousands of nanometers in size as the temperature increased. In vivo assays demonstrated that the polymer formed a gel depot _in situ_ in the subcutaneous layer. The apparent size (by volume) of the gel decreased to 30%-40% of the first day to seventh day, and the gel was completely cleared in 14 days from the implanted site. From H&E (hematoxylin and eosin) stained images, it was possible to observe blood capillaries inside the gel as well as collagen capsules around the implant, indicating marginal responses to the gel and good tissue compatibility of the gel. A similar thermogelling system (PAF-PEG) [99] was used to evaluate the effect of the stereochemistry (_i.e.,_ D-alanine/D-phenylalanine (PAF-D-PEG), non-natural amino acids or L-alanine/L-phenylalanine, (PAF-L-PEG) naturally occurring amino acids) on the _in vitro_/_in vivo_ degradation profiles, and tissue compatibility. Stereochemistry was found to play an important role in the polymer degradation from both _in vitro_ assays using enzyme solutions and _in vivo_ assays considering the duration of the gel in the subcutaneous layer of rats. Thus, PAF-L-PEG was degraded _in vitro_ by cathepsin B, and elastase, whereas PAF-D-PEG was quite stable against all the studied proteases (including collagenase). For both compounds, a transparent hydrogel was again formed upon the subcutaneous injection of the PAF-PEG aqueous polymer solution due to the temperature-sensitive sol-to-gel transition. The PAF-L-PEG gel was decreased in size after 15 days of implantation whereas a tight gel of PAF-D-PEG remained after this period of time suggesting the preferential biodegradation of PAF-L-PEG.