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The current barrier to clinical translation of small‐caliber tissue‐engineered vascular grafts (TEVGs) is the long‐term patency upon implantation in vivo. Key contributors are thrombosis and stenosis caused by inadequate mechanical graft properties and mismatch of hemodynamic conditions. Herein, the authors report on an approach for the fabrication of a mechanically tunable bilayered composite TEVGs. Using a combination of solution electrospinning (SES) and melt electrowriting (MEW), it is shown that the mechanical properties can be tailored and the natural J‐shape of the stress–strain relationship can be recapitulated. Upon cell seeding, the luminal surface of the composite SES layers permits the formation of a confluent mature endothelium. MEW fibers provide structural support to promote stacking and orientation of MSCs in a near‐circumferential native vessel like direction. By adjusting the ratios of poly(ε‐caprolactone) and poly(ester‐urethane) during the SES process, TEVGs with a range of tunable mechanical properties can be manufactured. Notably, this hybrid approach permits modulation of the radial tensile properties of TEVGs to approximate different native vessels. Overall, a strategy for the fabrication of TEVGs with mechanical properties resembling those of native vessels which can help to accommodate long‐term patency of TEVGs at various treatment sites in future applications is demonstrated. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was the preclinical and clinical evaluation of osteoinductive calcium phosphate with submicron surface topography as a bone graft substitute for maxillary sinus floor augmentation (MSFA). Material and Methods: A preclinical sheep model of MSFA was used to compare a calcium phosphate with submicron needle‐shaped topography (BCPN, MagnetOs Granules, Kuros Biosciences BV) to a calcium phosphate with submicron grain‐shaped topography (BCPG) and autologous bone graft (ABG) as controls. Secondly, a 10‐patient, prospective, randomized, controlled trial was performed to compare BCPN to ABG in MSFA with two‐stage implant placement. Results: The pre‐clinical study demonstrated that both BCPN and BCPG were highly biocompatible, supported bony ingrowth with direct bone apposition against the material, and exhibited bone formation as early as 3 weeks post‐implantation. However, BCPN demonstrated significantly more bone formation than BCPG at the study endpoint of 12 weeks. Only BCPN reached an equivalent amount of bone formation in the available space and a greater proportion of calcified material (bone + graft material) in the maxillary sinus compared to the "gold standard" ABG after 12 weeks. These results were validated in a small prospective clinical study, in which BCPN was found comparable to ABG in implant stability, bone height, new bone formation in trephine core biopsies, and overall clinical outcome. Conclusion: This translational work demonstrates that osteoinductive calcium phosphates are promising bone graft substitutes for MSFA, whereas their bone‐forming potential depends on the design of their surface features. Netherlands Trial Register, NL6436. [ABSTRACT FROM AUTHOR]

Clinical implementation of endochondral bone regeneration (EBR) would benefit from the engineering of devitalized cartilaginous constructs of allogeneic origins. Nevertheless, development of effective devitalization strategies that preserves extracellular matrix (ECM) is still challenging. The aim of this study is to investigate EBR induced by devitalized, soft callus‐mimetic spheroids. To challenge the translatability of this approach, the constructs are generated using an allogeneic cell source. Neo‐bone formation is evaluated in an immunocompetent rat model, subcutaneously and in a critical size femur defect. Living spheroids are used as controls. Also, the effect of spheroid maturation towards hypertrophy is evaluated. The devitalization procedure successfully induces cell death without affecting ECM composition or bioactivity. In vivo, a larger amount of neo‐bone formation is observed for the devitalized chondrogenic group both ectopically and orthotopically. In the femur defect, accelerated bone regeneration is observed in the devitalized chondrogenic group, where defect bridging is observed 4 weeks post‐implantation. The authors' results show, for the first time, a dramatic increase in the rate of bone formation induced by devitalized soft callus‐mimetics. These findings pave the way for the development of a new generation of allogeneic, "off‐the‐shelf" products for EBR, which are suitable for the treatment of every patient. [ABSTRACT FROM AUTHOR]

To facilitate true regeneration, a vascular graft should direct the evolution of a neovessel to obtain the function of a native vessel. For this, scaffolds have to permit the formation of an intraluminal endothelial cell monolayer, mimicking the tunica intima. In addition, when attempting to mimic a tunica media‐like outer layer, the stacking and orientation of vascular smooth muscle cells (vSMCs) should be recapitulated. An integral scaffold design that facilitates this has so far remained a challenge. A hybrid fabrication approach is introduced by combining solution electrospinning and melt electrowriting. This allows a tissue‐structure mimetic, hierarchically bilayered tubular scaffold, comprising an inner layer of randomly oriented dense fiber mesh and an outer layer of microfibers with controlled orientation. The scaffold supports the organization of a continuous luminal endothelial monolayer and oriented layers of vSM‐like cells in the media, thus facilitating control over specific and tissue‐mimetic cellular differentiation and support of the phenotypic morphology in the respective layers. Neither soluble factors nor a surface bioactivation of the scaffold is needed with this approach, demonstrating that heterotypic scaffold design can direct physiological tissue‐like cell organization and differentiation. [ABSTRACT FROM AUTHOR]