AP26196975 Fabrication of macroporous cell-laden polymers based on gelatin and hyaluronic acid

Relevance

Current advances in polymer science highlight the importance of developing biomaterials with well-defined architecture and tunable properties as biomedical materials. Biopolymers are biocompatible, biodegradable and inexpensive materials for hydrogels. They can incorporate biological signals such as peptides and growth factors, making them useful for tissue regeneration and controlled drug delivery. This project will develop gelatin and hyaluronic acid-based hydrogels using click chemistry, which will significantly improve the physicochemical properties of hydrogels and allow them to be used as scaffolds for tissue engineering and regenerative medicine. 3D MSC spheroids will be encapsulated in the hydrogel for further cell proliferation. The methods used are well-known and reliable, which gives a great chance to achieve the goal of this project.

Goals

Production of functionalized macroporous polymers based on gelatin and hyaluronic acid by the click reaction method for the proliferation of 3D MSC spheroids.

Expected results

At this stage, it is planned to determine the optimal synthesis conditions for obtaining a modified form of gelatin and hyaluronic acid, conduct physicochemical methods of studying the obtained prepolymers; isolate, cultivate and identify 3D MSCs spheroids. Appropriate equipmens and reagents will be purchased to accomplish these objectives.

Project investigator

Kudaibergen G.K. H-index = 6, ORCID ID – 0000-0002-0779-4099, Scopus ID – 57201858284

Research team members

Akhmetkarimova Zh.S., H-index = 2; Scopus ID – 55308246100; ORCID ID – 0000-0002-9782-5521

Arinova A.E.,

Mukhlis Sh.E. H-index = 2, Scopus Author ID 57218821067, ORCID 0000-0003-0528-1430

Publications and intellectual property related to the project

Akhmetkarimova Zh., Mukhlis Sh., Yildirim E., Zhumanazarova G., Ogay V., Altaeva N., Ashikbayeva M., Kudaibergen G. Emerging Trends in Photo-Crosslinkable Polymeric Biomaterials in Regenerative Medicine. Materials Today Chemistry. -2025-V50, 103172 https://doi.org/10.1016/j.mtchem.2025.103172 (IF=6.9, Q1, процентиль 88-й).

Achieved results

Chemical modification of gelatin and hyaluronic acid was carried out to introduce alkenyl and thiol groups into their structures. 4-Pentene anhydride was used to introduce unsaturated alkenyl groups, while thiol fragments were introduced via a reaction with N-acetylcysteine. Gelatin modification was carried out at pH ~9 and a temperature of 50°C. All syntheses were carried out in the dark, followed by purification of the samples by dialysis for 5 days against MilliQ. The resulting products were freeze-dried for 24 hours, and the isolated prepolymers were used for further physicochemical studies. Experiments have shown that reducing the amount of anhydride in the reaction medium results in the formation of softer, gel-like polymer matrices. Cross-linking of thiol-modified hyaluronic acid was carried out using EDC in the presence of sulfo-NHS. Functional groups were identified using IR and NMR spectroscopy. Mesenchymal stromal cells (MSCs) isolated from rat adipose tissue were cultured into 3D spheroids using the hanging drop method at a density of 30,000 cells per spheroid. After three days, the formation of stable cell spheroids was observed.