ECM-alginate microcarriers for alveolar regeneration in COPD

With 65 million patients globally, chronic obstructive pulmonary disease (COPD) is the third-leading cause of death. It is characterized by progressive and irreversible airflow limitation in the lung resulting from chronic airway inflammation and/or loss of alveolar tissue. Current treatments for COPD can only stop or slow down disease progression with no cure. The only option for end-stage disease is lung transplantation with restricted efficacy due to scarcity of donor lungs and high rejection rates. Hence, novel therapeutic strategies are urgently needed.

To address this, we aimed to develop alveolar type 2 (AT2) cell-bearing microcarriers derived from decellularized extracellular matrix (dECM) for alveolar regeneration in COPD lungs. Both AT2 cells and dECM have demonstrated regenerative effects in lung diseases in previous studies but were never reported for use in COPD therapy.

dECM was obtained with perfusion-based decellularization of murine, porcine, or human lungs followed by enzymatic digestion. Size-tunable monodispersed dECM-alginate microcarriers were formed in a custom-made microfluidic device.

The size of the microcarriers was directly dependent on the flow rate of alginate solution and dECM properties. Cell-bearing microcarriers with various alginate to dECM ratios could be generated ranging from sizes of 30 to 100 µm, which is in the range of individual mouse and human alveoli.

With our custom-built microfluidic chip, we are able to generate monodispersed dECM-alginate microcarriers which can be loaded with stem or progenitor cells. Microcarriers are versatile platforms that can support transplanted cells while providing healthy ECM in vivo, and thus has potential in COPD treatment.