Preparation Of Thermosensitive Injectable Hydrogels And Their Applications In Biomedical Field

In recent years,injectable hydrogels have gained increasing attention in the fields of drug delivery and tumor treatment.By injecting hydrogel formulations into irregular tissue defects formed after tumor resection,gels can be formed to fill the defects in response to physiological conditions,allowing for minimally invasive implantation and retention at the desired location.Such gels can be used to carry drugs,cells,and growth factors,enabling targeted therapy for tumors.The investigation of thermosensitive injectable implantable materials is a hot topic because temperature is stable inside the body and controllable outside.However,the main drawbacks of thermosensitive injectable hydrogels are limited mechanical strength and poor stability,which may be caused by polymer swelling or dissolution.To enhance the strength and stability of hydrogels,this study proposes the use of biocompatible cellulose ethers and bovine serum albumin as base materials.Through techniques such as functional molecule modification and non-covalent complexation,injectable hydrogel materials with excellent biocompatibility are developed.The feasibility of using these hydrogels for localized anti-tumor therapy and their effectiveness in combination with immunotherapy are evaluated.The specific research work is as follows:(1)By utilizing the characteristics of hydrophobic interactions and hydrogen bonding that respond to physiological temperature,we successfully constructed an injectable cellulose/bovine serum albumin hydrogel.This hydrogel,formed by HPC-g-AA and BSA,exhibits higher mechanical strength,temperature responsiveness,and sustained release properties.Compared to other treatment methods,HPC-g-AA/BSA injectable hydrogel overcomes the issue of needle clogging and can more easily reach deep tissues,thereby providing greater advantages in localized cancer therapy applications.Our in vitro and in vivo biocompatibility studies demonstrate that HPC-g-AA/BSA hydrogel exhibits excellent biocompatibility.The continuous release of DOX from the implanted gel near the tumor site leads to enhanced anticancer effects.Therefore,this injectable hydrogel with thermosensitivity and prolonged drug release has the potential to be utilized as a material for local drug delivery.Furthermore,this hydrogel holds broad application prospects in regenerative medicine,tissue engineering,and stimulus-responsive 3D cell culture.(2)Building upon the first study,we have developed a highly photothermal-responsive injectable hydrogel(ICG-HPC-g-AA/BSA)composed of cellulose and bovine serum albumin,with the incorporation of a photosensitizer.This hydrogel is loaded with tumor therapeutic drugs and can easily adhere to the tumor tissue upon implantation,enabling sustained drug delivery.Additionally,through intraperitoneal injection of immunotherapeutic drugs,it induces an in vivo anti-tumor immune response.Furthermore,the hydrogel generates photothermal effects under light irradiation,achieving the synergistic effects of chemotherapy,immunotherapy,and photothermal therapy.This effectively damages tumor tissues,offering potential advantages for localized cancer treatment.In vitro and in vivo biocompatibility studies demonstrate that the ICG-HPC-g-AA/BSA hydrogel exhibits no cytotoxicity to cells.Therefore,this injectable hydrogel with photothermal effects and drug-loading capabilities presents a new approach for current tumor therapy.