Pulmonary tissue-mimetic hydrogel niches for small cell lung cancer cell culture

Abstract

Although small cell lung cancer (SCLC) is characterized by early metastasis and high resistance to most anti-cancer therapeutics, resulting in poor prognosis, surgical treatment is unavailable for most patients. Instead, clinical treatment for SCLC patients relies largely on chemotherapy. Therefore, an analysis platform supporting research into the physiology of SCLC cells and novel anti-cancer drugs is strongly needed. Decellularized extracellular matrix (dECM) hydrogel is a promising candidate cell-culture system that could provide a tissue-specific environment. However, dECM-based hydrogels have limited property control, poor mechanical properties, and loss of components during decellularization. In this study, porcine decellularized lung tissue and hyaluronic acid (HA) were hybridized via photopolymerization to form a pulmonary tissue-mimetic hydrogel. dECM solution was obtained by decellularization and pepsin digestion. The dECM and HA were then modified with methacrylic moieties, which produced dECM–methacrylate (dECM–MA) and HA methacrylate (HA–MA). dECM–MA/HA–MA hydrogels were fabricated by photopolymerization using a photoinitiator under UV light irradiation. The mechanical properties of the dECM-based hydrogel were compared with those of native tissue. SCLC cells (NCI-H69) were encapsulated in multiple types of dECM-based hydrogels, and they exhibited higher cell proliferation, drug resistance, and CD44 expression in the presence of dECM–MA and HA–MA than in the control condition.