Novel cell-laden scaffolds embedded with theranostics for postoperative cancer patients

Abstract

Gastrointestinal (GI) tract cancer causes deaths of millions of people. Current cancer treatment includes surgery, chemotherapy and radiotherapy. For GI tract cancer patients after surgery, new tissues may need to be formed at the resection site for restoring body functions. Scaffold-based tissue engineering using nanofibrous scaffolds are highly promising for regenerating human tissues due to their distinctive advantages. Growth factors (GFs), such as basic fibroblast growth factors (bFGF), can be incorporated in electrospun nanofibrous scaffolds to promote GI tract regeneration. On the other hand, high cancer recurrence rates are a major problem. Early detection and effective treatment of recurrent cancer are vital for postoperative cancer patients. Nanotechnology revolutionizes medical treatments, and gold nanoparticle (AuNP)-based theranostics are attractive nanodevices which combine diagnostic and therapeutic functions in a single platform for cancers. Developing multifunctional medical devices that integrate theranostics with tissue engineering scaffolds is highly appealing for treating cancer patients. This PhD project aims to design and fabricate novel nanofibrous scaffolds incorporated with cells, growth factor and theranostics and investigate their performances in promoting tissue regeneration and providing cancer detection and treatment. Cell-laden and GF-encapsulated nanofibrous scaffolds were firstly made and studied. A novel concurrent emulsion electrospinning and co-axial electrospray technique was developed to incorporate live cells into GF-encapsulated scaffolds. Studies showed that rat gastric smooth muscle cells (rGSMCs) were successfully encapsulated in electrosprayed alginate hydrogel microspheres with high density and viability and that controlled and sustained release of bFGF from emulsion electrospun scaffolds was obtained. Triggered release of rGSMCs was achieved after microsphere break-down and released cells with high viability were randomly distributed inside scaffolds. Enhanced cell behaviors, including cell proliferation and cytoskeleton development, were observed for bFGF-containing scaffolds owing to the controlled bFGF release. It is demonstrated that cell-laded nanofibrous scaffolds incorporated with growth factor mimic native extracellular matrix of tissues and have high potential for enhancing tissue regeneration. AuNP-based theranostics were fabricated and investigated. Subsequently, theranostics-incorporated nanofibrous scaffolds were made via concurrent electrospinning and co-axial electrospray. Theranostics-encapsulated microspheres were randomly distributed inside nanofibrous scaffolds. A controlled release of AuNP-based theranostics was obtained and the morphology and structure of released theranostics remained the same as those of theranostics before encapsulation. The released theranostics could provide diagnostic and therapeutic functions, including strongly amplified Raman signals, active targeting, cellular imaging and photothermal therapy for HeLa cells which exhibit folate-receptor overexpression. Ultimately, novel cell-laden nanofibrous scaffolds incorporated with growth factor and theranositcs were produced via concurrent electrospinning and co-axial electrospray using a tri-system for fabrication. Cell-encapsulated alginate microspheres and theranostics-containing microspheres were randomly distributed inside scaffolds. Released rGSMCs inside scaffolds displayed high density and viability after hydrogel microsphere break-down, and enhanced cell behaviors, including cell proliferation and cytoskeleton development, were seen due to effects of released bFGF. Released theranostics inside scaffolds exhibited highly amplified Raman signals, cancer targeting and imaging, and photothermal therapy. The novel, multifunctional nanofibrous scaffolds developed in this project are highly promising for treating postoperative cancer patients by enhancing tissue regeneration and detecting and treating recurrent cancer.