Preparation And Properties Of Multifunctional Crosslinked Four-armed Degradable Polyester Materials

Poly(lactic-co-glycolic acid)(PLGA)and poy(glycolide-co-caprolactone)(PGCL)are common polyester materials in tissue engineering.PLGA and PGCL have been widely used in biomedical engineering fields such as surgical sutures and drug delivery due to their good biodegradability.However,PLGA has poor elastic deformation ability and acidosis and inflammatory reaction caused by accumulation of acidic by-products at the initial stage of degradation.Although PGCL has good elastic deformation ability,it has the disadvantages of slow degradation rate and poor biocompatibility.These problems are the key factors limiting the application of PLGA and PGCL in regenerative medicine.Therefore,aiming at the problems existing in PLGA and PGCL and combining the structural characteristics of four-arm polymer,this paper constructed a series of four-arm polyester materials with good biocompatibility,and studied the hydrophilicity,mechanical properties,crystallinity,and degradability of the materials.The main research contents of this paper are as follows:1.Synthesis of 4arm-PLGA-PGPE and physicochemical properties of electrospun membranes.The poor hydrophobicity and elastic deformation ability of PLGA are two problems that limit the application of PLGA electrospun membrane in tissue engineering.The suitable hydrophilicity and hydrophobicity of amphiphilic polymer and the stretchability of 4-armed structure are effective ways to solve the two problems of PLGA.The amphiphilic PLGA consists of two parts,one is hydrophilic polymer PGPE;The other part is a 4-armed PLGA with elastic structure.The amphiphilic 4arm-PLGA-PGPE was prepared by crosslinking the two parts,and the electrospun membrane was prepared by electrospinning technology.The results showed that compared to the electrospun membranes prepared by 4arm-PLGA and PLGA,the hydrophilicity and elastic deformation capacity of 4arm-PLGA-PGPE electrospun membranes were clearly improved,and it was more conducive to cell adhesion and growth on the surface of electrospun membranes.2.Synthesis of 4arm-PLGA-m BAM and its crystallinity and degradability propertie.The accumulation of acidic by-products at the initial stage of PLGA degradation is another problem that limits its application in tissue engineering.The initial degradation of PLGA first occurs in its amorphous region,the key to solving this problem is to reduce the amorphous content of the amorphous part of PLGA and improve the crystallinity of PLGA.In this experiment,the symmetrical structure of4arm-PLGA was utilized to form a high crystalline PLGA by controlling the content of crosslinking agent.The crystal nucleus of dendritic branched polymer(DHP)and 4armPLGA-m BAM with crosslinking agent were formed simultaneously in the solution,and PLGA with high crystallinity was obtained by the induction of crystal nucleus.Compared with the crystallinity of PLGA obtained by isothermal annealing,the crystallinity of PLGA obtained by isothermal annealing is usually less than 50%,and the crystallinity of 4arm-PLGA-m BAM prepared in this chapter can reach 78%,which is superior to that of PLGA prepared by isothermal annealing.The results show that the degradation rate of PLGA can be controlled by controlling the crystallinity of 4armPLGA-m BAM.At the same time,crystallization also delay the production of lactic acid at the initial stage of degradation,which has the potential to resolve local inflammation and acidosis caused by PLGA degradation.3.Synthesis of 4arm-PLGA-PEG and its structure and crystallization properties.Tissue engineering materials usually require certain porosity to promote cell growth and tissue repair.However,the traditional preparation method of porous materials is not suitable for the preparation of porous crystalline PLGA.Considering difficulties in preparing porous structure of crystalline PLGA,a new method was proposed in this study by using the swelling behavior and recrystallization process.According to the swelling characteristics of amorphous region in crystals,the swelling process can be realized by proper solvent during recrystallization,and the porous structure can be relalized by removing solvent.The results show that the amorphous part of 4armPLGA-PEG could keep swelling by using hexafluoro-isopropyl alcohol(HFIP)as the solvent during recrystallization,and the porous crystalline 4arm-PLGA-PEG can be obtained by freeze-drying to remove the solvent.The porous crystalline 4arm-PLGAPEG not only retained the properties of crystalline PLGA,but also had higher porosity and more appropriate pore size,making it further conducive to cell growth,and proposed a new method for the preparation of porous PLGA with higher crystallinity.4.Synthesis of 4arm-PGCL-BLPD and its biological properties and degradation.PLGA has similar mechanical properties to cancellous bone,but in the repair of vessel,skin,nerve,and abdominal wall defects,there are higher requirements of material elasticity.It was found from previous studies that PLGA could not meet these requirements,so PGCL was used in this study to prepare suitable materials for elastic tissues.In view of the 4arm-PGCL has problems of high hydrophobicity,difficultly in forming and slow degradation rate,hydrophilic crosslinking can solve these problems well.The hydrophilic lysine was used to prepare the crosslinking agent BLPD,and the amphiphilic 4arm-PGCL-BLPD was then prepared by crosslinking 4arm-PGCL with BLPD.Physical and chemical characterization indicates that the cross-linking help4arm-PGCL-BLPD easier to form,and the hydrophilicty and degradation rate were improved with the introduction of hydrophilic chain segement.Through cell experiments,it was also discovered that lysine-containing 4arm-PGCL-BLPD had better biocompatibility than PGCL,which reached the level of blank control group,higher than 80% of traditional PGCL,which broadened the application prospect of PGCL in tissue engineering.