Breathing life into engineered tissues using oxygen-releasing biomaterials

Abstract

Engineering three-dimensional (3D) tissues in clinically relevant sizes have demonstrated to be an effective solution to bridge the gap between organ demand and the dearth of compatible organ donors. A major challenge to the clinical translation of tissue-engineered constructs is the lack of vasculature to support an adequate supply of oxygen and nutrients post-implantation. Previous efforts to improve the vascularization of engineered tissues have not been commensurate to meeting the oxygen demands of implanted constructs during the process of homogeneous integration with the host. Maintaining cell viability and metabolic activity during this period is imperative to the survival and functionality of the engineered tissues. As a corollary, there has been a shift in the scientific impetus beyond improving vascularization. Strategies to engineer biomaterials that encapsulate cells and provide the sustained release of oxygen over time are now being explored. This review summarizes different types of oxygen-releasing biomaterials, strategies for their fabrication, and approaches to meet the oxygen requirements in various tissue engineering applications, including cardiac, skin, bone, cartilage, pancreas, and muscle regeneration.

Hydroxyapatite‐Incorporated Composite Gels Improve Mechanical Properties and Bioactivity of Bone Scaffolds

“…Hydrogels are prevalently used in tissue engineering to support the growth and proliferation of various cell types within 3D tissue constructs. [ 1–7 ] Load‐bearing and hard tissue constructs that are used in bone and cartilage tissue engineering require mechanically strong scaffolds to support cell differentiation and mineral deposition. [ 8–10 ] The commonly used biomaterials, such as ceramics and metals, are mechanically robust but are compatible with only certain cell cultures.…”

Turning Nature’s own processes into design strategies for living bone implant biomanufacturing: a decade of Developmental Engineering

“…Large cartilaginous constructs (Ø 10 mm × 6 mm) cultured in flow-through perfusion bioreactors in channeled alginate hydrogels demonstrate the capacity to obtain homogenously differentiated large structures [ 159 ]. Moreover, to overcome increasing mass transport limitations in larger constructs, efforts have been made to design and develop advanced oxygen-generating materials [ 171 ], multi-chamber bioreactor configurations [ 172 ] and 3D biofabrication techniques (e.g. printing in suspension baths or fused filament fabrication 3D printing) to provide optimal diffusion capabilities through tailored permeability and pre-vascularization strategies [ 173 , 174 ].…”

Human Erbb2-induced Erk Activity Robustly Stimulates Cycling and Functional Remodeling of Rat and Human Cardiomyocytes

“…Similar to hiPSC-CM and NRVM monolayers, all studied mitogens except caYap8SA increased EdU incorporation in NRVM cardiobundles, with cahErbb2 showing the strongest effect ( Figure 3C). We then assessed morphological and functional characteristics of cardiobundles and found that cahErbb2 transduction uniquely increased both the total cross-sectional area (CSA, Figure 3D) and F-actin + (CM) area of cardiobundles, leading to the formation of a necrotic core (devoid of Hoechst-positive nuclei; Figure 3E), likely caused by limited diffusion of oxygen into the center of the tissue (Suvarnapathaki, Wu, Lantigua, Nguyen, & Camci-Unal, 2019). We also observed increased vimentin + CSA, indicating increased fibroblast abundance ( Figure 3F).…”