Studies On Fabrication Of Tissue Repair Bio-adhesives And Property Regulation

Tissue damages caused by traffic accidents,diseases and surgical operations all need to be repaired.However,traditional surgical closure techniques involve the use of invasive techniques like sutures,staples,or clips,which often result in secondary tissue damage,microbial infection or poor cosmetic.Therefore,tissue adhesives have recently been used in patients to seal and repair tissue wounds.Mussels are well-known for their extraordinary capacity to adhere onto different surfaces.The researchers have found that the mussel byssus adhesive proteins contain abundant catechol groups.Thus,catechol derivatives with superior adhesion were used to modify biopolymers and polysaccharides.However,there are still some problems such as poor cohesion and insufficient adhesive strength.Some studies have shown that the adhesive strength between adhesive materials and substrates not only depends on the force of the interface bonds between adhesive materials and substrates,but also depends on the adhesive strength caused by the molecular chain structure of adhesive materials.Herein,this thesis focuses on the preparation of the catechins derivatives modified polysaccharide for improving the adhesion property.By further structural regulation,the hydrogel adhesives with high cohesive strength and adhesive strength could be obtained through several different methods.Adhesion strength between adhesive hydrogels and tissues,gelation time,rheological properties,mechanical properties,swelling properties,degradation rates,cell cytotoxicity and animals living tissue adhesive properties were investigated in detail.Fabrication of catechol-modified chitosan oligosaccharide hydrogel adhesives and property regulation.To improve the adhesion property,catechol-modified chitosan oligosaccharide?CSD?was synthesized by grafting 2-?3,4-dihydroxyphenyl?propionic acid?DPA?onto CS by the amide reaction.The chemical structure and substitution degree of CSD were characterized by FTIR and ¹H-NMR,and the maximum substitution degree reached 26%.Then,CSD was reacted with PEGDGE by ring-opening reaction between PEGDGE and CS and the CSD-PEG hydrogel adhesives were prepared by adjusting the ratios of PEGDGE and CSD.The microstructure,adhesive property,mechanical property,swelling property,degradability,drug loading and release property,cytotoxicity and tissue repair property were investigated in details.The experimental results indicated as follows.The CSD-PEG adhesive hydrogels showed the highest adhesive strength to porcine skin tissue at 157.5 kPa.Compared with commercial fibrin glue?8.0 kPa?,the adhesive strength of CSD-PEG adhesive hydrogels was improved to 20 times.In addition,CSD-PEG adhesive hydrogels had good degradability and drug loading and release property.After 30 days of in vitro degradation,the degradation rate of CSD-PEG adhesive hydrogels was about 90%.The maximum equilibrium swelling rate of CSD-PEG adhesive hydrogels was 299%,which can meet the requirements in vivo.MTT assay indicated that CSD-PEG adhesive hydrogels presented no cytotoxicity and the cell survival rate was above 90%.Moreover,animal experiments demonstrated that CSD-PEG adhesive hydrogels had excellent tissue adhesive properties,which can effectively promote wound repair and tissue regeneration.1.Fabrication of injectable adhesive hydrogels based on polysaccharide and property regulation.In order to promote the surgical operations more convenient and facilitate the adhesives more suitable match the defect tissue,adhesive hydrogels with rapid injectable based on polysaccharide were prepared for tissue repair.Oxidized dextran?ODE?was obtained by oxidation reaction.ODE-CS adhesive hydrogels with rapid injectable were formed by the Schiff base reaction between ODE and CS.Then,in order to promote the adhesion property of adhesive hydrogels,dopamine was added into the ODE-CS adhesives to prepare ODE-DA-CS adhesive hydrogels.Moreover,double crosslinking DN-Na IO₄ and DN-FeCl₃ adhesives were further crosslinked by NaIO₄ and FeCl₃.To study the effects of oxidation degree of dextran,DA and crosslinking agents,the gelation time,microstructure,adhesive property,mechanical property,swelling property,degradability and cytotoxicity of the hydrogels were characterized.The experimental results indicated as follows:Injectable adhesive hydrogels have been rapidly gelation within 1 min.Adhesive hydrogels have excellent adhesive properties.After modified by DA and crosslinking agents,the adhesive properties of the double crosslinking adhesive hydrogels DN-NaIO₄ and DN-FeCl₃ have been significantly increased and the highest adhesive strength reached up to 345 kPa.Compared with the CSD-PEG adhesive hydrogels?135 kPa?prepared in the previous chapter,the adhesive strength of injectable adhesive hydrogels was increased by 2.5 times.The adhesive strength of injectable adhesive hydrogels was 43 times higher than that of commercial Fibrin glue?8.0kPa?.In addition,the mechanical strength of the double crosslinking adhesive hydrogels DN-Na IO₄ and DN-FeCl₃ have been improved after secondary modification by crosslinking agents and adhesive hydrogels have good swelling property and degradability.Cytotoxicity tests have demonstrated that adhesive hydrogels present no cytotoxicity,benefiting its further application in wound dressing.