PDMS-PEG Block Copolymer and Pretreatment for Arresting Drug Absorption in Microphysiological Devices.

Poly(dimethylsiloxane) (PDMS) is a commonly used polymer in organ-on-a-chip devices and microphysiological systems. However, due to its hydrophobicity and permeability, it absorbs drug compounds, preventing accurate drug screening applications. Here, we developed an effective and facile method to prevent the absorption of drugs by utilizing a PDMS-PEG block copolymer additive and drug pretreatment. First, we incorporated a PDMS-PEG block copolymer into PDMS to address its inherent hydrophobicity. Next, we addressed the permeability of PDMS by eliminating the concentration gradient via pretreatment of the PDMS with the drug prior to experimentally testing drug absorption. The combined use of a PDMS-PEG block copolymer with drug pretreatment resulted in a mean reduction of drug absorption by 91.6% in the optimal condition. Finally, we demonstrated that the proposed method can be applied to prevent drug absorption in a PDMS-based cardiac microphysiological system, enabling more accurate drug studies.

Engineering Three-Dimensional Vascularized Cardiac Tissues.

Heart disease is one of the largest burdens to human health worldwide and has very limited therapeutic options. Engineered three-dimensional (3D) vascularized cardiac tissues have shown promise in rescuing cardiac function in diseased hearts and may serve as a whole organ replacement in the future. One of the major obstacles in reconstructing these thick myocardial tissues to a clinically applicable scale is the integration of functional vascular networks capable of providing oxygen and nutrients throughout whole engineered constructs. Without perfusion of oxygen and nutrient flow throughout the entire engineered tissue not only is tissue viability compromised, but also overall tissue functionality is lost. There are many supporting technologies and approaches that have been developed to create vascular networks such as 3D bioprinting, co-culturing hydrogels, and incorporation of soluble angiogenic factors. In this state-of-the-art review, we discuss some of the most current engineered vascular cardiac tissues reported in the literature and future directions in the field. Impact statement The field of cardiac tissue engineering is rapidly evolving and is now closer than ever to having engineered tissue models capable of predicting preclinical responses to therapeutics, modeling diseases, and being used as a means of rescuing cardiac function following injuries to the native myocardium. However, a major obstacle of engineering thick cardiac tissue remains to be the integration of functional vasculature. In this review, we highlight seminal and recently published works that have influenced and pushed the field of cardiac tissue engineering toward achieving vascularized functional tissues.