Laser patterning on polymeric materials is considered a green and rapid manufacturing process with low material selection barrier and high adjustability. Unlike microelectromechanical systems (MEMS), it is a highly flexible processing method, especially useful for prototyping. This study focuses on the development of polymer surface modification method using a 193 nm excimer laser system for the design and fabrication of a microfluidic system similar to that of natural vasculatures. Besides from poly(dimethyl siloxane) (PDMS), laser ablation on biodegradable polymeric material, poly(glycerol sebacate) (PGS) and poly(1,3-diamino-2-hydroxypropane-co-polyol sebacate) (APS) are investigated. Parameters of laser ablation and fabrication techniques to create microchannels are discussed. The results show that nano/micro-sized fractures and cracks are generally observed across PDMS surface after laser ablation, but not on PGS and APS surfaces. The widths of channels are more precise on PGS and APS than those on PDMS. Laser beam size and channel depth are high correlation with a linear relationship. Repeated laser ablations on the same position of scaffolds reveal that the ablation efficiencies and edge quality on PGS and APS are higher than on PDMS, suggesting the high applicability of direct laser machining to PGS and APS. To ensure stable ablation efficiency, effects of defocus distance into polymer surfaces toward laser ablation stability are investigated. The depth of channel is related to the ratio of firing frequency and ablation progression speed. The hydrodynamic simulation of channels suggests that natural blood vessel is similar to the laser patterned U-shaped channels, and the resulting micro-patterns are highly applicable in the field of micro-fabrication and biomedical engineering.

As acrylated polymers become more widely used in additive manufacturing, their potential applications toward biomedicine also raise the demand for biodegradable, photocurable polymeric materials. Polycaprolactone diacrylate (PCLDA) and poly(ethylene glycol) diacrylate (PEGDA) are two popular choices of materials for stereolithography (SLA) and digital light processing additive manufacturing (DLP-AM), and have been applied to many biomedical related research. However, both materials are known to degrade at a relatively low rate in vivo, limiting their applications in biomedical engineering. In this work, biodegradable, photocurable copolymers are introduced by copolymerizing PCLDA and/or PEGDA with poly(glycerol sebacate) acrylate (PGSA) to form a network polymer. Two main factors are discussed: the effect of degree of acrylation in PGSA and the weight ratio between the prepolymers toward the mechanical and degradation properties. It is found that by blending prepolymers with various degree of acrylation and at various weight ratios, the viscosity of the prepolymers remains stable, and are even more 3D printable than pure substances. The formation of various copolymers yielded a database with selectable Young’s moduli between 0.67–10.54 MPa, and the overall degradation rate was significantly higher than pure substance. In addition, it is shown that copolymers fabricated by DLP-AM fabrication presents higher mechanical strength than those fabricated via direct UV exposure. With the tunable mechanical and degradation properties, the photocurable, biodegradable copolymers are expected to enable a wider application of additive manufacturing toward tissue engineering.

Objective: Stromal barriers, such as the abundant desmoplastic stroma that is characteristic of pancreatic ductal adenocarcinoma (PDAC), can block the delivery and decrease the tumour-penetrating ability of therapeutics such as tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), which can selectively induce cancer cell apoptosis. This study aimed to develop a TRAIL-based nanotherapy that not only eliminated the extracellular matrix barrier to increase TRAIL delivery into tumours but also blocked antiapoptotic mechanisms to overcome TRAIL resistance in PDAC. Design: Nitric oxide (NO) plays a role in preventing tissue desmoplasia and could thus be delivered to disrupt the stromal barrier and improve TRAIL delivery in PDAC. We applied an in vitro–in vivo combinatorial phage display technique to identify novel peptide ligands to target the desmoplastic stroma in both murine and human orthotopic PDAC. We then constructed a stroma-targeted nanogel modified with phage display-identified tumour stroma-targeting peptides to co-deliver NO and TRAIL to PDAC and examined the anticancer effect in three-dimensional spheroid cultures in vitro and in orthotopic PDAC models in vivo . Results: The delivery of NO to the PDAC tumour stroma resulted in reprogramming of activated pancreatic stellate cells, alleviation of tumour desmoplasia and downregulation of antiapoptotic BCL-2 protein expression, thereby facilitating tumour penetration by TRAIL and substantially enhancing the antitumour efficacy of TRAIL therapy. Conclusion: The co-delivery of TRAIL and NO by a stroma-targeted nanogel that remodels the fibrotic tumour microenvironment and suppresses tumour growth has the potential to be translated into a safe and promising treatment for PDAC.