Font Size: a A A

The Investigating Of Degradable Biological Membrane Preventing Tissue Adhesion And Tumor Recurrence

Posted on:2018-01-02Degree:DoctorType:Dissertation
Country:ChinaCandidate:W WuFull Text:PDF
GTID:1314330542959305Subject:Surgery
Abstract/Summary:PDF Full Text Request
It is aninteractive process for repair and regeneration of diseased tissue,including curing disease,tissue regeneration,preventing inflammation and so on.Scaffold is an excellent carrier which can deliver drug meanwhile support cell growth.However,the process of regeneration of diseased tissue is stagewise.Tissue adhesion is caused by tissue fluid exudation with several of reasons,which contains lots of tissue fibrin then the fibrin intertwined to form a fibrin network with capillaries inside.Capillaries can delivery nutrition to the newly formed tissue,keep new tissue growing,and extend new tissue structure then forming the fibrin network between tissue,and then generating fibrous adhesions causing function disorder.In general,the prevention and treatment of the above-mentioned tissue adhesion are: reducing the inflammatory response and exudation;inhibiting the activity of fibroblasts;application of non-biological materials,biomaterials,drug thin film,and cytokines.In addition,there may be present residual tumor cells after local tumor resection,so drug release is required to inhibit the growth of these cells.Because the local tissue of tumor cells is generally acidic,the use of acid-sensitive drug carrier can release anti-tumor drug accurately and inhibit the growth of tumor cell without affecting the normal cell growth.Moreover it is necessary to inhibit the growth of tumor cells and repair the damaged tissue namely use scaffold to support normal cell growth in the tumor resection site.Therefore,from the perspective of biological materials,a designed material with excellentbiocompatibility and tissue matching can prevent tissue adhesion and inhibition of tumor recurrence without influencing normal tissue regeneration and reconstruction.To meet the needs of the integrated process of treatment and rehabilitation.This paper will design various degradable biomaterials meanwhileinvestigateitspotential application on preventing tissue adhesion and inhibiting remaining tumor cell.Firstly,matural hydrogels are promising membranes used to prevent intra-abdominal adhesion formation.Currently,natural hydrogels such as chitosan-,gelatin-or hyaluronic acid-based hydrogels are utilized to prevent adhesion.However,their uncontrollable mechanical properties and quick degradation result in an unsatisfying short effect-time.In this study,a photocrosslinkable gelatin(GelMA)prepolymer was synthesized and developed for preventing intra-abdominal adhesion formation.Hydrogel membranes based on GelMA showed easy-handleability,non-toxic degradation and a long-lasting excellent barrier effect for up to 1 month.We have found that a 20% GelMA hydrogel membrane concentration could be employed to meet the requirements of excellent barrier effect,and the implantation of GelMA hydrogel membranes in rat abdominal cavities in experimental groups led to a considerable decrease in adhesion formation in comparison to the control group.The present study established the initial foundation for a novel and practical approach to prevent abdominal adhesion in surgery.Secondly,there is a high local recurrence(LR)rate in breast-conserving therapy(BCT)and enhancement of the local treatment is promising as a way to improve this.Thus we propose a drug delivery system using doxorubicin(DOX)-loaded mesoporous silica nanoparticle composite nanofibers which can release anti-tumor drugs in two phases—burst release in the early stage and sustained release at a later stage—to reduce the LR of BCT.In the present study,we designed a novel composite nanofibrous scaffold to realize the efficient release of drugs by loading both DOX and DOX-loaded mesoporous silica nanoparticles into an electrospun PLLA nanofibrous scaffold.Invitro results demonstrated that this kind of nanomaterial can release DOX in two phases,and the results of in vivo experiments showed that this hybrid nanomaterial significantly inhibited the tumor growth in a solid tumor model.Histopathological examination demonstrated that the apoptosis of tumor cells in the treated group over a 10 week period was significant.The anticancer effects were also accompanied with decreased expression of Bcl-2 and TNF-?,along with up-regulation of Bax,Fas and the activation of caspase-3 levels.The present study illustrates that the mesoporous silica nanoparticle composite nanofibrous scaffold could have anti-tumorproperties and could be further developed as adjuvant therapeutic protocols for the treatment of cancer.In summary,this paper is mainly focuses on preventing tissue adhesion and inhibiting remaining tumor cell in general surgery,designing crosslinking degradable hydrogel membrane and drug-loaded fibers respectively.Above all,to build a biodegradable gelatin gel,obtaining a soft and operable hydrogel film,so as to prevent abdominal adhesions with broadapplication.Further,based on the biomaterials,it is promising to construct a drug-loaded fibrous membrane with drug-controlled release,drug-loaded fibrous membrane is expected to inhibit remaining tumor cell and as a carrier for cell growth meanwhile long release anti-tumor drugs.
Keywords/Search Tags:Tissue adhesion, biomaterials, hydrogel, drug release, tumor
PDF Full Text Request
Related items