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1. Personalized Computational Models of Tissue-Rearrangement in the Scalp Predict the Mechanical Stress Signature of Rotation Flaps

   https://doi.org/10.1177/1055665620954094  

   Lee, Taeksang ; Turin, Sergey Y. ; Stowers, Casey ; Gosain, Arun K. ; Tepole, Adrian Buganza ( April 2021 , The Cleft Palate-Craniofacial Journal)

   null (Ed.)

   Objective: To elucidate the mechanics of scalp rotation flaps through 3D imaging and computational modeling. Excessive tension near a wound or sutured region can delay wound healing or trigger complications. Measuring tension in the operating room is challenging, instead, noninvasive methods to improve surgical planning are needed. Design: Multi-view stereo allows creation of 3D patient-specific geometries based on a set of photographs. The patient-specific 3D geometry is imported into a finite element (FE) platform to perform a virtual procedure. The simulation is compared with the clinical outcome. Additional simulations quantify the effect of individual flap parameters on the resulting tension distribution. Participants: Rotation flaps for reconstruction of scalp defects following melanoma resection in 2 cases are presented. Rotation flaps were designed without preoperative FE preparation. Main Outcome Measure: Tension distribution over the operated region. Results: The tension from FE shows peaks at the base and distal ends of the scalp rotation flap. The predicted geometry from the simulation aligns with postoperative photographs. Simulations exploring the flap design parameters show variation in the tension. Lower tensions were achieved when rotation was oriented with respect to skin tension lines (horizontal tissue fibers) and smaller rotation angles. Conclusions: Tension distribution following rotation of scalp flaps can be predicted through personalized FE simulations. Flaps can be designed to reduce tension using FE, which may greatly improve the reliability of scalp reconstruction in craniofacial surgery, critical in complex cases when scalp reconstruction is essential for coverage of hardware, implants, and/or bone graft. 

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2. Vascularization strategies for skin tissue engineering

   https://doi.org/10.1039/D0BM00266F  

   Amirsadeghi, Armin ; Jafari, Arman ; Eggermont, Loek J. ; Hashemi, Seyedeh-Sara ; Bencherif, Sidi A. ; Khorram, Mohammad ( July 2020 , Biomaterials Science)

   null (Ed.)

   A number of challenges in skin grafting for wound healing have drawn researchers to focus on skin tissue engineering as an alternative solution. The core idea of tissue engineering is to use scaffolds, cells, and/or bioactive molecules to help the skin to properly recover from injuries. Over the past decades, the field has significantly evolved, developing various strategies to accelerate and improve skin regeneration. However, there are still several concerns that should be addressed. Among these limitations, vascularization is known as a critical challenge that needs thorough consideration. Delayed wound healing of large defects results in an insufficient vascular network and ultimately ischemia. Recent advances in the field of tissue engineering paved the way to improve vascularization of skin substitutes. Broadly, these solutions can be classified into two categories as (1) use of growth factors, reactive oxygen species-inducing nanoparticles, and stem cells to promote angiogenesis, and (2) in vitro or in vivo prevascularization of skin grafts. This review summarizes the state-of-the-art approaches, their limitations, and highlights the latest advances in therapeutic vascularization strategies for skin tissue engineering. 

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3. 3D printing‐based full‐scale human brain for diverse applications

   https://doi.org/10.1002/brx2.5  

   Hua, Weijian ; Zhang, Cheng ; Raymond, Lily ; Mitchell, Kellen ; Wen, Lai ; Yang, Ying ; Zhao, Danyang ; Liu, Shu ; Jin, Yifei ( April 2023 , Brain‐X)

   Surgery is the most frequent treatment for patients with brain tumors. The construction of full‐scale human brain models, which is still challenging to realize via current manufacturing techniques, can effectively train surgeons before brain tumor surgeries. This paper aims to develop a set of three‐dimensional (3D) printing approaches to fabricate customized full‐scale human brain models for surgery training as well as specialized brain patches for wound healing after surgery. First, a brain patch designed to fit a wound's shape and size can be easily printed in and collected from a stimuli‐responsive yield‐stress support bath. Then, an inverse 3D printing strategy, called “peeling‐boiled‐eggs,” is proposed to fabricate full‐scale human brain models. In this strategy, the contour layer of a brain model is printed using a sacrificial ink to envelop the target brain core within a photocurable yield‐stress support bath. After crosslinking the contour layer, the as‐printed model can be harvested from the bath to photo crosslink the brain core, which can be eventually released by liquefying the contour layer. Both the brain patch and full‐scale human brain model are successfully printed to mimic the scenario of wound healing after removing a brain tumor, validating the effectiveness of the proposed 3D printing approaches.

    

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4. Spatially Guided Construction of Multilayered Epidermal Models Recapturing Structural Hierarchy and Cell–Cell Junctions

   https://doi.org/10.1002/smsc.202200051  

   Zhai, Haiwei ; Jin, Xiaowei ; Minnick, Grayson ; Rosenbohm, Jordan ; Hafiz, Mohammed Abdul Haleem ; Yang, Ruiguo ; Meng, Fanben ( September 2022 , Small Science)

   A current challenge in 3D bioprinting of skin equivalents is to recreate the distinct basal and suprabasal layers and promote their direct interactions. Such a structural arrangement is essential to establish 3D stratified epidermis disease models, such as for the autoimmune skin disease pemphigus vulgaris (PV), which targets the cell–cell junctions at the interface of the basal and suprabasal layers. Inspired by epithelial regeneration in wound healing, a method that combines 3D bioprinting and spatially guided self‐reorganization of keratinocytes is developed to recapture the fine structural hierarchy that lies in the deep layers of the epidermis. Herein, keratinocyte‐laden fibrin hydrogels are bioprinted to create geographical cues, guiding dynamic self‐reorganization of cells through collective migration, keratinocyte differentiation, and vertical expansion. This process results in a region of self‐organized multilayers (SOMs) that contain the basal‐to‐suprabasal transition, marked by the expressed levels of different types of keratins that indicate differentiation. Finally, the reconstructed skin tissue as an in vitro platform to study the pathogenic effects of PV is demonstrated, illuminating a significant difference in cell–cell junction dissociation induced by PV antibodies in different epidermis layers, which indicates their applications in the preclinical test of possible therapies.

    

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5. Mechano-biological and bio-mechanical pathways in cutaneous wound healing

   https://doi.org/10.1371/journal.pcbi.1010902  

   Pensalfini, Marco ; Tepole, Adrian Buganza ( March 2023 , PLOS Computational Biology)

   Marsden, Alison L. (Ed.)

   Injuries to the skin heal through coordinated action of fibroblast-mediated extracellular matrix (ECM) deposition, ECM remodeling, and wound contraction. Defects involving the dermis result in fibrotic scars featuring increased stiffness and altered collagen content and organization. Although computational models are crucial to unravel the underlying biochemical and biophysical mechanisms, simulations of the evolving wound biomechanics are seldom benchmarked against measurements. Here, we leverage recent quantifications of local tissue stiffness in murine wounds to refine a previously-proposed systems-mechanobiological finite-element model. Fibroblasts are considered as the main cell type involved in ECM remodeling and wound contraction. Tissue rebuilding is coordinated by the release and diffusion of a cytokine wave,e.g.TGF-β, itself developed in response to an earlier inflammatory signal triggered by platelet aggregation. We calibrate a model of the evolving wound biomechanics through a custom-developed hierarchical Bayesian inverse analysis procedure. Further calibration is based on published biochemical and morphological murine wound healing data over a 21-day healing period. The calibrated model recapitulates the temporal evolution of: inflammatory signal, fibroblast infiltration, collagen buildup, and wound contraction. Moreover, it enablesin silicohypothesis testing, which we explore by: (i) quantifying the alteration of wound contraction profiles corresponding to the measured variability in local wound stiffness; (ii) proposing alternative constitutive links connecting the dynamics of the biochemical fields to the evolving mechanical properties; (iii) discussing the plausibility of a stretch-vs.stiffness-mediated mechanobiological coupling. Ultimately, our model challenges the current understanding of wound biomechanics and mechanobiology, beside offering a versatile tool to explore and eventually control scar fibrosis after injury.

    

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