## 4 Functional Properties of Chitosan and Derivatives
### Biomedical and Pharmaceutical Functions  
Regarding the previous section, CS is a unique cationic biocompatible and biodegradable (see Section 5) polysaccharide that can be modified, as required, according to the needed end-use application. This is particularly true for biomedical and pharmaceutical applications ranging from drug delivery systems [164] to functional biomaterials [165], also considering tissue engineering [166], cell culturing [167], regenerative scaffolds [168], wound healing [169], smart hydrogels [170], active nanoparticles [171], anticoagulants [172], gene therapy [173], etc. (Figure 9). This list is obviously non-exhaustive regarding a short search on Scopus with more than 120 recent documents (2018-2019) using \"biomedical\" AND \"pharmaceutical\" AND \"chitosan\" AND \"derivative\" keywords. Figure 8: Structure of lipo-chitooligosaccharides produced by EJ355 strain from _S. meliloti_[159]. Very recently, [PERSON] et al. [174] published a deep and comprehensive review that scientist readers should adress to fully understand the progress of CS chemistry for use in biomedical fields, as well as the paper of [PERSON] et al. [4], which highlighted the need for an integral approach to comprehend all the potential of CS and its derivatives. Additionnaly, [PERSON] et al. [175] detailed in their review the implications of the molecular diversity of chitin, CS, and some derivatives. The authors suggested the strong potential of CS-based nanomaterials to enhance nanobiotechnology in the future. [PERSON] et al. [176] placed an emphasis on various biological activities of chitol oligosaccharidesacharics (COS). COS with low DP (\(<20\)) seemed to be the most prefered bases for prospecting biomedical properties due to their excellent solubility, absorbability, and capacity to cross physiological barriers [177]. Additional lipophilic groups were described to greatly increase biocompatibilty [178; 179]. COS and associated derivatives were reported for their uses in DNA/drug delivery system, [180], tissue regeneration [177], anticancer/antitumor [180], anti-HIV(1) [181], anti-hypertensive [180], or Alzheimer's disease [182]. _N,N_-trimethyl CS (TMC) was reported as a quaternized hydrophilic derivative for assembling new pharmaceutical nano-structures [182], but also for applications in tissue engineering [183]. These authors prepared a multifunctional nanohybrid scaffold able, on one hand, to _in vitro_ load/release bioactive molecules (e.g., LMW heparin), and on the other hand, to play the role of a platform for the proliferation of soft tissue, extracellular matrix, and specific cells involved in adipogenesis. Furthermore, some authors have developed new nanoparticulate formulations with a TMC derivative, such as [PERSON] et al. [184], who loaded LMW protamine on TMC-coated nanoparticles for oral administration. This formulation clearly allowed an increase of intestinal permeability and efficient effects on the intestinal mucus layer. As another example, TMC micelles can be prepared to overcome subasorption and solulibitly problems of specific active molecules, such as insoluble alkaloid, osthole, etc. [185; 186]. The use of nanoparticles is not new and current papers deal with specific derivatives such as carboxymethyl CS (CMCS), which are soluble in both acidic and alkaline solutions, for designing nanotechnology-bases systems based on stimulus-based, diffusion, swelling, or erosion-controlled release [187]. Beside, [PERSON] et al. [188] recently showed the potential of thiolated methylated dimethylaminobenzyl CS as a delivery vehicle. This statement was validated on Human Embryonic  
Figure 9: Various applications of chitosan and derivatives in biomedical and pharmaceutical fields. Kidney cells (Hek293) and the results revealed an improvement of solubility and disponibility, and no significant cytotoxicity.