3D printed gelatin/PTMC core/shell scaffolds with NIR laser-tuned drug/ biomolecule release for cancer therapy and uterine regeneration

Surgical resection is an efficient treatment for cancerous tissues and uterine fibroids in the women uterus. However, the insufficiency of clinical interventions could result in tumor recurrence, and the defective tissues remained would cause intrauterine adhesions (IUAs) and further affect reproduction capacity. In this study, 3D printed hydrogel/poly(L-lactide-co-trimethylene carbonate) (PLLA-co-TMC, "PTMC" in short) core/shell scaffolds with NIR-tuned doxorubicin hydrochloride (DOX) and estradiol (E2) dual release were designed and fabricated for cancer therapy and uterine regeneration. Gelatin (Gel) and DOX were homogeneously mixed and then 3D printed to form Gel-DOX scaffolds. Gel-DOX scaffolds were then immersed in PTMC-PDA@E2 solution to fabricate Gel-DOX/PTMC-PDA@E2 core/shell scaffolds. Consequently, Gel-DOX/PTMC-PDA@E2 scaffolds could release DOX and E2 in a chronological manner, firstly delivering DOX assisted by phototherapy (PTT) to effectively kill Hela cells and then sustainably releasing E2 to promote uterine tissue regeneration. In vitro experiments showed that core/shell scaffolds exhibited excellent anticancer efficiency through the synergy of DOX release and hyperthermia ablation. Moreover, E2 could be sustainably released for over 28 days in vitro to promote the proliferation of bone marrow-derived mesenchymal stem cells (BMSCs). The novel Gel-DOX/PTMCPDA@E2 core/shell scaffolds have therefore exhibited potential promise for the treatment of cancer therapy and uterine regeneration.