Research over the past decade on the cell-biomaterial interface has shifted to the third dimension. Besides mimicking the native extracellular environment by 3D cell culture, hydrogels offer the possibility to generate well-defined 3D biofabricated tissue analogs. In this context, gelatin-methacryloyl (gelMA) hydrogels have recently gained increased attention. This interest is sparked by the combination of the inherent bioactivity of gelatin and the physicochemical tailorability of photo-crosslinkable hydrogels. GelMA is a versatile matrix that can be used to engineer tissue analogs ranging from vasculature to cartilage and bone. Convergence of biological and biofabrication approaches is necessary to progress from merely proving cell functionality or construct shape fidelity towards regenerating tissues. GelMA has a critical pioneering role in this process and could be used to accelerate the development of clinically relevant applications.

Giant cell granuloma of the jaw is a benign lesion that may cause local destruction of bone and displacement of teeth. The common therapy is curettage or resection, which may be associated with loss of teeth and, in younger patients, loss of dental germs. An alternative treatment has recently been introduced, in which patients receive a daily dose of calcitonin. Four patients who have been treated with calcitonin in various concentrations for at least 1 year are reported.

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.

Background and ObjectivesEvaluation of mandibular reconstructions with free fibula flaps. Identification of factors associated with major recipient site complications, that is, necessitating surgical intervention under general anaesthesia.MethodsSeventy‐nine reconstructions were included. The following factors were analyzed: fixation type, number of osteotomies, site of defect (bilateral/unilateral), surgeon, sex, ASA classification, continuous smoking, pathological N‐stage, age, defect size, flap ischemic time, and postoperative radiotherapy. Proportional hazards regression was used to test the effect on the time between reconstruction and intervention.ResultsSixty‐nine (87%) of the 79 fibula flaps were successful at the last follow‐up. Forty‐eight major recipient site complications occurred in 41 reconstructions. Nineteen complications required surgical intervention within six weeks and were mostly vascular problems, necessitating immediate intervention. These early complications were associated with defects crossing the midline, with an estimated relative risk of 5.3 (CI 1.1‐20, P = 0.01). Twenty‐nine complications required surgical intervention more than 6 weeks after the reconstruction. These late complications generally occurred after months or years, and were associated with smoking, with an estimated relative risk of 2.8 (CI 1.0‐8.3, P = 0.05).ConclusionsFibula flaps crossing the midline have a higher risk of early major recipient site complications than unilateral reconstructions. Smoking increases the risk of late complications.

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For creating functional tissue analogues in tissue engineering, stem cells require very specific 3D microenvironments to thrive and mature. Demanding (stem) cell types that are used nowadays can find such an environment in a heterogeneous protein mixture with the trade name Matrigel. Several variations of synthetic hydrogel platforms composed of poly(ethylene glycol) (PEG), which are spiked with peptides, have been recently developed and shown equivalence to Matrigel for stem cell differentiation. Here a clinically relevant hydrogel platform, based on PEG and gelatin, which even outperforms Matrigel when targeting 3D prevascularized bone and liver organoid tissue engineering models is presented. The hybrid hydrogel with natural and synthetic components stimulates efficient cell differentiation, superior to Matrigel models. Furthermore, the strength of this hydrogel lies in the option to covalently incorporate unmodified proteins. These results demonstrate how a hybrid hydrogel platform with intermediate biological complexity, when compared to existing biological materials and synthetic PEG‐peptide approaches, can efficiently support tissue development from human primary cells.

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