3D Printing Of Hydrogel Scaffolds For Breast Cancer Therapy And Mammoplastic Repair

Breast cancer is one of the most serious diseases threatening women’s life and health.Surgical resection is still one of the general clinical approaches for breast cancer treatment.Especially,breast-conserving surgery is the preferred choice for more and more doctors and patients due to the minimally invasive and lower surgical complications.Recently,the combination therapy including breast-conserving surgery and postoperative comprehensive treatment has become one of the main strategies for the treatment of early breast cancer.However,surgical resection for breast cancer treatment generally caused two major issues: 1)high local recurrence risk and metastasis of breast cancer;2)partial loss of the breast tissues.In addition,chemotherapy and radiotherapy usually cause severe pain and side effects for patients.Thus,photothermal therapy(PTT)has attracted great attention for cancer therapy due to the low side effects.For the treatment of the local recurrence of breast cancer after surgery,hydrogels with PTT ability not only can kill cancer effectively,but also fill up the tissue defects.Specifically,hydrogel scaffolds with controlled macro pores have the capability for tissue repair and regeneration.Therefore,3D printed hydrogel scaffolds with macro pores would be the prefered choice for breast cancer therapy and mammoplastic repair after surgery.In this thesis,we fabricated hydrogel scaffolds with bifunctions of photothermal therapy and tissue repair by 3D printing.Polydopamine(PDA)with catechol structure and alginate were prepared as bioinks for 3D printing of scaffolds,because PDA has good photothermal effects and alginate is a widely used bioink for 3D printing.Then,the potential application of the printed hydrogel scaffolds in cancer therapy and tissue repair was discussed.Additionally,smart drug delivery systems can effectively minimize the distribution and side effects of drugs in the whole body.Furthermore,combination therapy generally can kill cancer effectively with low side effects.In order to enhance the therapeutic effect,another type of hydrogel scaffolds with core-shell fiber structure was prepared by using coaxial 3D printing technology.The core part was temperature-sensitive hydrogels loading with therapeutic drugs.The shell part was highly concentrated hydrogels with good photothermaleffects.The shell part could increase the temperature of the core part to trigger drug release under near infrared(NIR)irradiation,as well as could prevent the ineffective leakage of the drug from the fiber wall.Then,the core-shell hydrogel scaffold could achieve NIR-triggered on-demand drug delivery.On the other hand,core-shell fiber scaffolds could be applied for adipose tissue engineering after the drug-loaded core hydrogels were released.The designed hydrogel scaffolds had the functions of chemo-photothermal therapy and smart drug delivery,indicating that the scaffolds might be the potential candidates for cancer therapy and tissue repair of breast cancer after surgery.The main contents and results of this thesis are as follow:1.Inspired by marine mussels,dopamine(DA)was used to modify alginate to form alginate-dopamine(Alg-DA)conjugates,and then mixtures of Alg-DA conjugates and DA were prepared as inks for 3D printing of scaffolds.DA monomer could be oxidized and self-polymerized to polydopamine(PDA)under alkaline conditions.During this process,PDA nanoparticles were partly knotted with Alg-DA by chemical and physical interactions.The scaffolds were fabricated using simple and biocompatible materials with individual-designed structure and macropores,as well as outstanding photothermal effect and enhanced cell proliferation ability,might be a potential option for breast cancer treatment and tissue repair after surgery.The structures and mechanical properties of the scaffolds were characterized;as well the cancer therapy effects of the scaffolds were evaluated by mouse 4T1 tumor model.The ability for soft tissue repair was studied by seeding human breast cells on the scaffolds,and the proliferation of cells was measured.2.Core-shell hydrogel scaffolds with NIR-triggered on-demand drug delivery were fabricated by core-shell coaxial 3D printing.Mixtures of polydopamine and concentrated alginate inks(15.3 wt%)were prepared for the shell layer,and drug-loaded temperature-sensitive hydrogels for the core part of scaffolds.Under NIR irradiation,PDA with excellent photothermal effect could raise the temperature of core-shell fibers,which induced the gel-sol transition of the core gels,and subsequently resulted in the drug release from the loosened hydrogel network.After the core gels were released,the scaffolds served as platforms for adipose tissue engineering.Thus,core-shell fiber scaffolds with NIR-triggered drug delivery could be used for chemo-photothermal combination therapy of cancer andfilling the cavity of tissues after surgical resection.Our study would provide a useful platform for the treatment of superficial epidermal tumors and tissue repair.