## 4 Potential Applications of Peptide-Synthetic Polymer Hybrids
### Crosslinked Hydrogels and Scaffolds for Tissue Engineering
Moreover, the histocompatibility around the _in situ_ formed gels of PAF-L-PEG and PAF-D-PEG was also compared by the H&E staining method. Collagen capsules were observed around the gel for both systems. However, the collagen capsule was thicker for PAF-D-PEG than PAF-L-PEG, indicating milder tissue irritation or acute inflammation for material constituted by natural L-amino acids. Polyalanine-poloxamer-polyalanine (PA-PLX-PA) block copolymers have been developed for this kind of application [100]. Specifically hybrids were constituted by a segment where a central hydrophilic moiety of poly(ethylene oxide) was flanked by two hydrophobic moieties of poly(propylene oxide). Peptides derived from L-alanine, DL-alanine, and their mixture (L/DL-alanine) were used in order to to control the secondary structure as well as their resulting fibrous nanostructure. The resulting hydrogel was proved to be an excellent 3D system for the proliferation and differentiation of chondrocytes. With a reverse thermal gelling property, current polypeptide aqueous solution appears a very promising minimally-invasive injectable tissue engineering scaffold. [PERSON] and coworkers [101] observed that long range nanoffibrous orientation was attained by a self-assembling ionic complex between the above explained (+)-charged amphiphilic peptide block copolymer (PA-PLX-PA) and a (-)-charged hyaluronic acid (HA). Cell proliferation and biomarker expression for articular cartilage were significantly improved when the PA-PLX-PA/HA complex system was employed. In particular, noticeable cell clustering was observed in the PA-PLX-PA/HA complex system with the long range nanoffibrous structure. This point is highly interesting since suggests a new method for developing a nanofibrous structure using an amphiphilic peptide block copolymer and demonstrates its potential uses as a unique biomimetic cell-culture matrix. A poly(ethylene glycol)-_b_-poly(L-alanine) (PEG-L-PA) gel encapsulating fibroblasts was investigated for wound healing as a new thermogel application [102]. The fibroblasts were encapsulated by the temperature sensitive sol-to-gel transition of the polymer aqueous solution. Under the _in vitro_ three-dimensional (3D) cell culture condition, the new thermogel was comparable with a commercially available control (_i.e._, a soluble extract of basement membrane proteins derived from the rat tumor tissue named Matrigel) for cell proliferation and was significantly better than this control for collagen types I and III formation. Furthermore, wound healing experiments demonstrated that PEG-L-PA not only accelerated the wound closure but also improved epithelialization and the formation of skin appendages such as keratinocytes(epidermis), hair follicles, and sebaceous glands. Other related works based on peptide/poly(ethylene glycol) (PEG) or other copolymer hydrogels have been carried out lately. For example, thermoresponsive hydrogels constituted of a telechelic PEG end-capped with hydrophobic dipeptides (_i.e._, phenylalanine-phenylalanine (Phe-Phe) or tyrosine-tyrosine (Tyr-Tyr) were proposed to be used in responsive delivery or encapsulation for biomedical applications [103]. In another study, PEG was replaced with an amphiphilic ABA-block copolymer (Pluronic F127) consisting in PEG end blocks and a poly(propylene oxide) (PPO) center block, which was able to self-assemble into micelles with a water-incompatible compartment that was segregated from the aqueous exterior by the PEG shell. An alanine (A)-based peptide (AK2) doped with charged lysines (K) with a sequence of (AKA\({}_{3}\)KA)\({}_{2}\) was selected from the crosslinking regions of the natural elastin as a starting point for the hydrogel formation. It was prepared via covalent linkages between the terminal vinyl sulfone groups of the synthetic block copolymer and the lysine amines of the peptide [104]. By heating up to 60 \({}^{\circ}\)C the Michael-type addition reaction was accelerated and led to the formation of stable viscoelastic hydrogels.