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Modular tissue engineering is based on the cells’ innate ability to create bottom-up supramolecular assemblies with efficiency and efficacy still unmatched by man-made devices. Although the regenerative potential of such tissue substitutes has been documented in preclinical and clinical setting, the prolonged culture time required to develop an implantable device is associated with phenotypic drift and/or cell senescence. Herein, we demonstrate that macromolecular crowding significantly enhances extracellular matrix deposition in human bone marrow mesenchymal stem cell culture at both 20% and 2% oxygen tension. Although hypoxia inducible factor - 1α was activated at 2% oxygen tension, increased extracellular matrix synthesis was not observed. The expression of surface markers and transcription factors was not affected as a function of oxygen tension and macromolecular crowding. The multilineage potential was also maintained, albeit adipogenic differentiation was significantly reduced in low oxygen tension cultures, chondrogenic differentiation was significantly increased in macromolecularly crowded cultures and osteogenic differentiation was not affected as a function of oxygen tension and macromolecular crowding. Collectively, these data pave the way for the development of bottom-up tissue equivalents based on physiologically relevant developmental processes.

Arterial obstruction leading to ischemia causes a reduction of oxygen and nutrient supply to distal tissues. The physiological response to tissue ischemia triggers a cascade of events that results in the development of accessory vasculature to increase local tissue perfusion and to salvage tissue. However, this adaptive mechanism of repair is suboptimal in some patients. Therapeutic angiogenesis aims to stimulate new blood vessel formation via the local administration of proangiogenic agents or cell therapy products (CTPs). In this review, we provide a summary of the current understanding of in vitro models for assessing the angiogenic potential of a product.

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Diabetes mellitus (DM) is associated with an elevated risk of post‐operative complications. The impact it has on patients living with DM following hip fracture surgery (HFS) is not completely understood and may represent a predictor of increased mortality. This study investigates the impact of DM, gender, American Society of Anaesthesiologists (ASA) grade, and fracture location, on the outcome of HFS in Ireland. The Hospital Inpatient Enquiry (HIPE) database records all fragility hip fractures within Galway University Hospital. Retrospective data collection was performed over a 3‐year period. Data collected included patient age, gender, date of HFS, anatomical fracture location, type of operation, ASA grade, DM status, and mortality. A database of 650 individuals was created including 461 females and 189 males, with an average group age of 80.2 ± 9.3 years. Results showed a significantly higher incidence of hip fractures in males with DM (19.57%) than females with DM (12.36%) (χ2 test, p = 0.020). Cox regression survival analysis indicated that DM status and ASA grade were the two main independent predictors of patient survival following HFS. Nevertheless, when examining the combined impact of gender and DM status on survival after HFS, results showed that survival post HFS differed significantly with gender and presence of DM (log‐rank test, p < 0.001), with males with DM performing worse than females with DM (p = 0.021) or males without DM (p = 0.001). This gender and disease‐associated outcome should prompt an early multi‐disciplinary team approach to the management of hip fractures in patients with DM. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:834‐842, 2020