Polyurethane scaffold-based 3D lung cancer model recapitulates in vivo tumor biological behavior for nanoparticulate drug screening.

Lung cancer is the leading cause of cancer mortality worldwide. Preclinical studies in lung cancer hold the promise of screening for effective antitumor agents, but mechanistic studies and drug discovery based on 2D cell models have a high failure rate in getting to the clinic. Thus, there is an urgent need to explore more reliable and effective in vitro lung cancer models. Here, we prepared a series of three-dimensional (3D) waterborne biodegradable polyurethane (WBPU) scaffolds as substrates to establish biomimetic tumor models in vitro. These 3D WBPU scaffolds were porous and could absorb large amounts of free water, facilitating the exchange of substances (nutrients and metabolic waste) and cell growth. The scaffolds at wet state could simulate the mechanics (elastic modulus ∼1.9 kPa) and morphology (porous structures) of lung tissue and exhibit good biocompatibility. A549 lung cancer cells showed adherent growth pattern and rapidly formed 3D spheroids on WBPU scaffolds. Our results showed that the scaffold-based 3D lung cancer model promoted the expression of anti-apoptotic and epithelial-mesenchymal transition-related genes, giving it a more moderate growth and adhesion pattern compared to 2D cells. In addition, WBPU scaffold-established 3D lung cancer model revealed a closer expression of proteins to in vivo tumor, including tumor stem cell markers, cell proliferation, apoptosis, invasion and tumor resistance proteins. Based on these features, we further demonstrated that the 3D lung cancer model established by the WBPU scaffold was very similar to the in vivo tumor in terms of both resistance and tolerance to nanoparticulate drugs. Taken together, WBPU scaffold-based lung cancer model could better mimic the growth, microenvironment and drug response of tumor in vivo. This emerging 3D culture system holds promise to shorten the formulation cycle of individualized treatments and reduce the use of animals while providing valid research data for clinical trials.

Janus functional electrospun polyurethane fibrous membranes for periodontal tissue regeneration.

The guided tissue regeneration (GTR) technique with GTR membranes is an efficient method for repairing periodontal defects. Conventional periodontal membranes act as physical barriers that resist the growth of fibroblasts, epithelial cells, and connective tissue. However, they cannot facilitate the regeneration of periodontal tissue. To address this issue, the exploitation of novel GTR membranes with bioactive functions based on therapeutic requirements is critical. Herein, we exploited a biodegradable bilayer polyurethane fibrous membrane by uniaxial electrostatic spinning to construct two sides with Janus properties by integrating the bioactive molecule dopamine (DA) and antimicrobial Gemini quaternary ammonium salt (QAS). The DA-containing side, located inside the injury, can effectively promote cell adhesion and mesenchymal stem cell growth as well as support mineralization and antioxidant properties, which are beneficial for bone regeneration. The QAS-containing side, located on the outer surface of the injury, endows antibacterial properties and limits fibroblast adhesion and growth on its surface owing to its strong hydrophilicity. An in vivo study demonstrates that the Janus polyurethane fibrous membrane can significantly promote the regeneration of periodontal defects in rats. Owing to its superior mechanical properties and biocompatibility, this polyurethane fibrous membrane has potential applications in the field of periodontal regeneration.

A bioinspired Janus polyurethane membrane for potential periodontal tissue regeneration.

Guided tissue regeneration (GTR) is the main therapeutic method for periodontal tissue regeneration. The key to the GTR strategy is the membrane which can assist the reconstruction of bone tissue in the periodontal defect and prevent the migration of epithelium and fibroblasts to the defect. However, the existing periodontal membrane cannot effectively promote periodontal tissue regeneration due to the limited bioactivity and physicochemical function. Here, we developed a bioinspired degradable polyurethane membrane with Janus surface morphology by integrating bioactive dopamine (DA) and an antibacterial Gemini quaternary ammonium salt (QAS). The Janus surface of the membrane is fabricated through spontaneous microphase separation, resulting from the different migration of functional segments between the air-contact upper surface with enriched antibacterial QAS and the substrate-contact bottom with enriched bioactive DA. The smooth surface of the upper membrane used to face the soft tissues can reduce cell adhesion to suppress the migration of fibroblasts, while the rough surface with a topological micro-pit structure of the bottom side facing the bone has excellent function of autonomic mineralization and cell adhesion to promote bone tissue reconstruction. In addition, the membrane containing the antibacterial QAS shows excellent antibacterial effect on common oral pathogens, such as S. aureus and S. mutans. Moreover, the specific dopamine group also endows the membrane with excellent antioxidant efficiency. In vivo research shows that this Janus polyurethane membrane can effectively promote periodontal tissue regeneration in a rat periodontal defect model. Combined with its excellent mechanical properties and biocompatibility, the polyurethane membrane is a promising material for potential periodontal tissue regeneration.