# Alginate Modification and Lectin-Conjugation Approach to Synthesize the Mucoadhesive Matrix
## 6 Conclusions and Future Outlook  
The availability of hydroxyl and carboxyl groups in the alignates chain for chemical reactions opens up the possibility for advanced chemical modification. Chemical modification is the preferred method for generating the alginate derivatives, having enhanced and altogether new characteristics. The range of this modification establishes a compelling potential for tailoring the next generation of alginate-based biomaterial for particular applications [1,3].  
The advent of carbonyl activating reagents, such as 1-ethyl-3-(3-dimethyl aminopropyl) carbodimide (EDC) with N-hydroxysuccinimide (NHS) in carbodimide chemistry, has permitted selective modification of alignates. This allows modification of bulk properties and the attachment of functional substituent. Further, \({}^{1}\)H-nuclear magnetic resonance investigation revealed the formation of urea derivative by-products from the coupling reaction between alignates and arginine-glycine-aspartate (RGD) [60]. Filtration could only partly remove this urea derivative and leave the N-acyl urea bound to alignates to stay on the resulting polymer.  
On the other hand, the oxidation of alignates is a functionalization by the reaction on the hydroxyl groups. This selective modification on the hydroxyl moieties is able to maintain the capacity of alginate derivatives to spontaneously form hydrogels in the presence of divalent ions [3]. Together with reductive amination, these methods are suggested as a more efficient way to functionalize the alginate's biopolymer [67]. The oxidation gives access to controlled biopolymer degradability, forming a cross-linking reaction and bioactive conjugation via reductive amination on the now-available aldehyde functional groups.  
The alginate functionalization with peptide through oxidation and reductive amination is one of the most attractive developments in the alginate bioconjugation field. This finding opens up new possibilities to conjugate the alginate with bioactive substances through the hydroxyl groups. These are forming more degradable polymers without losing their attractive features.  
Despite the alginate derivative's potential in numerous biomedical applications, the regiocontrol and chemoselectivity issues in alginate derivative synthesis raise challenges, as do the number of clinical translations. However, as further remarkable features of alginate-based materials in the biomedical field emerge, more studies are warranted to improve the synthesis strategies, analytics, characterization, and technology of alignates and their derivatives-based material.  
Conceptualization, A.P.P., F.P., S.H. and M.C.; selection of references, A.P.P., F.P. and M.C.; writing--original draft preparation, A.P.P. and F.P.; writing--review and editing, A.P.P., F.P., S.H. and M.C.; supervision, S.H. and M.C.; funding acquisition, F.P. and M.C. All authors have read and agreed to the published version of the manuscript.  
This research was funded by Directorate General of Higher Education (DIKTI) Ministry of Education and Culture, Republic of Indonesia, NKB-58/UN2.RST/HKP05.00/2020 and the APC was funded by the Engineering and Technology institute Groningen, University of Groningen.  
Not applicable.  
The authors declare no conflict of interest.