Porous Polymeric Microspheres With Controllable Pore Diameters for Tissue Engineered Lung Tumor Model Development

Abstract

Complex cell cultures are more representative of in vivo conditions than conventionally used monolayer cultures, and are hence being investigated for predictive screening of therapeutic agents. Poly lactide co-glycolide (PLGA) polymer is frequently used in the development of porous substrates for complex cell culture. Substrates or scaffolds with highly interconnected, micrometric pores have been shown to positively impact tissue model formation by enhancing cell attachment and infiltration. We report a novel alginate microsphere (AMS)-based controlled pore formation method for the development of porous, biodegradable PLGA microspheres (PPMS), for tissue engineered lung tumor model development. The AMS porogen, non-porous PLGA microspheres (PLGAMS) and PPMS had spherical morphology (mean diameters: 10.3 ± 4, 79 ± 21.8, and 103 ± 30 µm, respectively). The PPMS had relatively uniform pores and a porosity of 45.5%. Degradation studies show that PPMS effectively maintained their structural integrity with time whereas PLGAMS showed shrunken morphology. The optimized cell seeding density on PPMS was 25 × 10 3 cells/mg of particles/well. Collagen coating on PPMS significantly enhanced the attachment and proliferation of co-cultures of A549 lung adenocarcinoma and MRC-5 lung fibroblast cells. Preliminary proof-ofconcept drug screening studies using mono-and combination anti-cancer therapies demonstrated that the tissue-engineered lung tumor model had a significantly higher resistance to the tested drugs than the monolayer co-cultures. These studies indicate that the PPMS with controllable pore diameters may be a suitable platform for the development of complex tumor cultures for early in vitro drug screening applications.

Advancement of Scaffold-Based 3D Cellular Models in Cancer Tissue Engineering: An Update

“…The cells in the scaffold showed an increased cell attachment, proliferation and drug resistance in response to the anti-cancer drugs, doxorubicin, cisplatin, curcumin, paclitaxel, etoposide, and gemcitabine when compared with the 2D culture. The collagen-PPMS scaffold model is a potential in vitro lung tumor model which could be used for evaluating cancer progression, screening drugs, and elucidating the mechanism of drug resistance ( 69 ).…”

The Potential Contribution of Biopolymeric Particles in Lung Tissue Regeneration of COVID-19 Patients

“…PLGA is often used to create porous substrates for complex cell cultures. Substrates or scaffolds with densely packed micrometric pores help build tissue models [124]. Noxious nitric oxide provides antimicrobial action and biofilm dispersion.…”

Porous Crosslinked Zwitterionic Microparticles Based on Glycidyl Methacrylate and N-Vinylimidazole as Possible Drug Delivery Systems

“…Porous materials as spherical particles have received a lot of attention lately for the numerous directions in which they can be used, such as in catalytic reactions, separation processes, consumer products (such as water softeners), biomedical devices, coating additives and controlled drug release systems [ 1 , 2 , 3 , 4 , 5 ]. As a polymer matrix, both natural [ 6 , 7 , 8 , 9 , 10 ] and synthetic polymers [ 11 , 12 , 13 , 14 , 15 ] can be used for the synthesis of porous microparticles.…”