Preparation Of Chitosan Nanofiber Based Hydrogel And Its Application In Biomedical Materials

Chitosan physical hydrogel is often used as an ideal medical biomaterial for medical dressings,biological tissue engineering and other biomedical materials due to their porous reticulated three-dimensional structure,non-toxicity,degradability and excellent biocompatibility.However,due to the poor mechanical properties and low cell adhesion of pure chitosan physical hydrogels,these drawbacks greatly limit its further application in the field of clinical and biomaterials.In this paper,a chitosan physical hydrogel with good mechanical properties was proposed and constructed from chitosan nanofibres(CSNFs)prepared by the papermaking method,and further introduced with hyaluronic acid(HA)to obtain good p Hresponsive properties,showing a wide range of application prospects in the field of medical dressings and tissue engineering.In addition,due to the properties of chitosan nanofibres,chitosan nanofibre hydrogels cross-linked with sulphate were prepared in a single step after interaction with sulphuric acid.The details are as follows.Chitosan nanofiber hydrogels were successfully prepared by micro-dissolution method using chitosan nanofiber prepared by grinding technique in papermaking process,and the effect of the concentration of chitosan nanofiber on the properties of hydrogels was investigated.The method can largely reduce the concentration of the cross-linking agent β-glycerophosphate disodium salt(β-GP),which can avoid the toxicity caused by the high concentration of β-GP.By adjusting the content of CSNFs,the gel formation time can be controlled and hydrogels of chitosan nanofibres with different pore sizes can be prepared.As the content of chitosan nanofibres increases,the gel formation time of the hydrogels gradually shortens and the internal pore aperture becomes smaller.The prepared chitosan nanofiber gels have high elastic modulus up to 10 KPa,and the internal structure of chitosan nanofibre hydrogels is stable in the frequency range of 0.1 HZ～100 HZ,which can maintain their physical properties during normal handling and movement.In addition,in the temperature range of 25℃～65℃,chitosan nanofibre hydrogel has good thermal stability and can maintain its physical properties stably in human body.In order to further extend the application of hydrogels prepared using papermaking method chitosan nanofibres,this paper prepared intelligent hydrogels with excellent mechanical properties and p H response by using chitosan nanofibers as raw materials and introducing hyaluronic acid.The introduction of hyaluronic acid reduces the gel time,endows the hydrogel with good p H response to drug release,and further improves the mechanical properties of chitosan physical hydrogel.After embedding the drug in it,the cumulative drug release was less than 30% under neutral conditions and no further release was achieved after 5h.Under acidic conditions,a large amount of drug release was promoted,with a sustained release of up to 30 h and a cumulative release of up to nearly 100%.Through kinetic simulations,the drugs in hydrogels with 1.0% and 1.5% CSNFs at p H=4 was more consistent with a first-order model,with diffusion driven mainly by concentration differences.Drug release in the other hydrogels was consistent with the Ritger-Peppas model,with Fick diffusion dominating.In addition,hydrogels prepared from CSNFs made from papermaking with a rough surface showed better cell adhesion compared with the hydrogels prepared from chitosan powder.In this study,a physical hydrogel of chitosan cross-linked with sulphate was also prepared in one step by combining the properties of chitosan nanofibres from papermaking and using a certain concentration of sulphuric acid to interact with them.In the current method of preparing physical hydrogels using sulphate crosslinking,a uniform gel cannot be formed because the local crosslinking rate is too fast when using sulphate crosslinking.In this paper,due to the large specific surface area of the chitosan nanofibers,it has better dispersibility in water.After dropping sulfuric acid,the free amino groups on the chitosan are more likely to be protonated,and the sulfate radicals will quickly generate electrostatic adsorption with them.CSNFs are cross-linked while being acid-decomposed,and the entanglement between chitosan chains can quickly form a gel.The method is simple and rapid,and the prepared hydrogel has self-healing properties and can pass through a 0.45 mm injection needle.In summary,this paper is based on the physical hydrogel prepared by papermaking chitosan nanofibers with excellent mechanical properties and good biocompatibility.Preliminary studies found that the gel has good adhesion properties to cancer cells and the release of anti-cancer drugs loaded in the hydrogel can vary according to the p H value in tumour growth.These applications suggest that the hydrogel can be used as a functional wound dressing restored after surgery(especially tumour resection)and has potential applications in postoperative prevention and treatment such as promoting wound healing and removing residual lesion tissue from the wound.