Abstract
The micrometer scale sac-like alveoli are the most important and essential unit for gas exchange in the lung. Thus, design and fabrication of scaffolds for alveoli regeneration by tissue engineering approach should meet a few topography and functional requests such as large surface area, flexibility, and high gas permeability to their native counterpart. Testing the gas permeability of scaffolds through a fast and simple technique is also highly demanded to assist new scaffold development. This study fabricated alveolus-like scaffolds with regular pore shape, high pore connectivity, and high porosity produced by inverse opal technique alongside randomly distrusted porous scaffolds by salt leaching technique from two different materials (polyurethane and poly(L-lactic acid)). The scaffold surface was modified by immobilization of VEGF. A facile and new technique based on the bubble meter principle enabling to measure the gas permeability of porous scaffolds conveniently has been developed specifically. The cellular response of the scaffolds was assessed by culturing with bone marrow mesenchymal stem cells and coculturing with lung epithelial NL20 and endothelial HUVECs. Our results showed that the newly designed gas permeability device provided rapid, nondestructive, reproducible, and accurate assessment of gas permeability of different scaffolds. The porous polyurethane scaffolds made by inverse opal method had much better gas permeability than other scaffolds used in this study. The cellular work indicated that with VEGF surface modification, polyurethane inverse opal scaffolds induced alveolus-like tissues and have promising application in lung tissue engineering.
Highlights
The prevalence of lung diseases has been increasing because of smoking, air pollution, and genetic disorders [1]
Chronic obstructive pulmonary disorder (COPD), acute lung injury/acute respiratory distress syndrome (ALI/ARDS), pulmonary hypertension (PH), cystic fibrosis (CF), and lung cancer are among the lung diseases with high mortality [2,3,4,5,6]
It can been seen that the microfluidic device generated uniform gelatin microspheres with diameter of 180 ± 18, 250 ± 25, and 310 ± 45 μm (Figures 3(a)– 3(c)) compared with the sieving method (250-350 μm, Figure 3(d))
Summary
The prevalence of lung diseases has been increasing because of smoking, air pollution (high dust and chemical particles in air), and genetic disorders [1]. Lung tissue transplantation is the gold standard for treating damaged lungs and helping to save lives. It is an effective and safe therapy for the patients suffering from a variety of end-stage pulmonary diseases. More than 50,000 adult lung transplants have been entered into the International Society of Heart and Lung Transplantation Registry by 2014 [7]. This treatment faces big challenges: shortage of donor organs, expensive surgery, and short transplant life due to chronic lung allograft dysfunction, along with the recurrence of the underlying pathology in some cases [8]. Tissue engineering approach which is able to generate biologically compatible substitutes to restore and support lung tissue functions [9] becomes a very promising therapy
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