In vitro models of the vasculature play an important role in biomedical discovery research, with diverse applications in vascular biology, drug discovery and tissue engineering. These models aim to replicate the conditions of the human vasculature including physical geometry, employing appropriate vascular cells exposed to physiological forces. However, vessel biology is complex, with multiple relevant cell types, precise 3D architectural arrangement, an array of biological cues and pressure, flow and shear forces that are difficult to replicate outside of the body. Vessel bioreactors typically comprise core modules, common to most systems: a 3D tubular scaffold to support cells, media and nutrient exchange for cell viability, a pumping module and sensor arrays for monitoring. In our comprehensive review of the literature, foundational elements such as maintenance of cell viability, nutrient exchange with flow, use of 3D scaffolds and basic sensing capabilities are well established. However, most bioreactor systems fail to adequately replicate combinations of physiological forces – pressure, shear, and flow – that are physiologically relevant. At the root of this deficiency is the field’s reliance on simple pumping systems designed for other applications, making it necessary to add resistors and compliance chambers to even approach human vascular conditions. As vascular biology research rapidly progressed it became increasingly clear that combinations of physical forces strongly influence cell phenotype, gene expression and in turn can be drivers of pathology. We highlight the need for renewed innovation in vascular bioreactor development with a focus on the importance of providing appropriate physiological forces in the same system.

Periosteum is a highly vascularized membrane lining the surface of bones. It plays essential roles in bone repair following injury and reconstruction following invasive surgeries. To broaden the use of periosteum, including for augmenting in vitro bone engineering and/or in vivo bone repair, we have developed an ex vivo perfusion bioreactor system to maintain the cellular viability and metabolism of surgically resected periosteal flaps. Each specimen was placed in a 3D printed bioreactor connected to a peristaltic pump designed for the optimal flow rates of tissue perfusate. Nutrients and oxygen were perfused via the periosteal arteries to mimic physiological conditions. Biochemical assays and histological staining indicate component cell viability after perfusion for almost 4 weeks. Our work provides the proof-of-concept of ex vivo periosteum perfusion for long-term tissue preservation, paving the way for innovative bone engineering approaches that use autotransplanted periosteum to enhance in vivo bone repair.