Milica Radisic

Significant advances in biomaterials, stem cell biology, and microscale technologies have enabled the fabrication of biologically relevant tissues and organs. Such tissues and organs, referred to as organ-on-a-chip (OOC) platforms, have emerged as a powerful tool in tissue analysis and disease modeling for biological and pharmacological applications. A variety of biomaterials are used in tissue fabrication providing multiple biological, structural, and mechanical cues in the regulation of cell behavior and tissue morphogenesis. Cells derived from humans enable the fabrication of personalized OOC platforms. Microscale technologies are specifically helpful in providing physiological microenvironments for tissues and organs. In this review, biomaterials, cells, and microscale technologies are described as essential components to construct OOC platforms. The latest developments in OOC platforms (e.g., liver, skeletal muscle, cardiac, cancer, lung, skin, bone, and brain) are then discussed as functional tools in simulating human physiology and metabolism. Future perspectives and major challenges in the development of OOC platforms toward accelerating clinical studies of drug discovery are finally highlighted.

Abstract Biomaterials are becoming increasingly crucial for healthcare solutions, with extensive use in the field of tissue engineering and drug delivery. After implantation, biomaterials trigger an immune response characterized by the recruitment of bone‐marrow‐derived proinflammatory macrophages that develop as the most abundant cell type surrounding the biomaterial. Chronic activation of this recruited macrophage population induces a foreign body reaction response and consequent biomaterial rejection. However, transition toward a proreparative phenotype is associated with biomaterial integration and tissue homeostasis restoration. In this review, the most relevant strategies that modulate biomaterial immune response are discussed, including mechanical properties, surface coatings, release of anti‐inflammatory molecules and cytokines, antibacterial features, origin and inner moieties of biomaterials, and cell crosstalk. Moreover, the role of tissue resident macrophages, an embryo‐derived macrophage population with a strong reparative potential, in promoting biomaterial tolerance will be reviewed. This provides new insights to better tune the reaction of the host immune system to implanted biomaterials in order to favor integration and increase the knowledge of macrophages as key players in tissue homeostasis.

Polyester biomaterials are used in tissue engineering as scaffolds for implantation of tissues developed in vitro. An ideal biodegradable elastomer for cardiac tissue engineering exhibits a relatively low Young's modulus, with high elongation and tensile strength. Here we describe a novel polyester biomaterial that exhibits improved elastic properties for cardiac tissue engineering applications. We synthesized poly(octamethylene maleate (anhydride) 1,2,4-butanetricarboxylate) (124 polymer) prepolymer gel in a one-step polycondensation reaction. The prepolymer was then molded as desired and exposed to ultraviolet (UV) light to produce a cross-linked elastomer. 124 polymer exhibited highly elastic properties under aqueous conditions that were tunable according to the UV light exposure, monomer composition, and porosity of the cured elastomer. Its elastomeric properties fell within the range of adult heart myocardium, but they could also be optimized for higher elasticity for weaker immature constructs. The polymer showed relatively stable degradation characteristics, both hydrolytically and in a cellular environment, suggesting maintenance of material properties as a scaffold support for potential tissue implants. When assessed for cell interaction, this polymer supported rat cardiac cell attachment in vitro as well as comparable acute in vivo host response when compared to poly(l-lactic acid) control. This suggests the potential applicability of this material as an elastomer for cardiac tissue engineered constructs.