bims-cateng Biomed News
on Cell and tissue engineering
Issue of 2023–11–26
six papers selected by
Chance Bowman, Dartmouth College
  1. Aligned Collagen Sponges with Tunable Pore Size for Skeletal Muscle Tissue Regeneration.
  2. Engineering large and geometrically controlled vascularized nerve tissue in collagen hydrogels to restore large-sized volumetric muscle loss.
  3. Chemical Transdifferentiation of Somatic Cells: Unleashing the Power of Small Molecules.
  4. Biomimetic Conductive Hydrogel Scaffolds with Anisotropy And Electrical Stimulation for in Vivo Skeletal Muscle Reconstruction.
  5. Atomic force microscopy-mediated mechanobiological profiling of complex human tissues.
  6. Development of a Cre-recombination-based color-switching reporter system for cell fusion detection.
  1. J Funct Biomater. 2023 Oct 24. pii: 533. [Epub ahead of print]14(11):
    Aligned Collagen Sponges with Tunable Pore Size for Skeletal Muscle Tissue Regeneration.
    Natalie G Kozan, Sean Caswell, Milan Patel, Jonathan M Grasman.
      Volumetric muscle loss (VML) is a traumatic injury where at least 20% of the mass of a skeletal muscle has been destroyed and functionality is lost. The standard treatment for VML, autologous tissue transfer, is limited as approximately 1 in 10 grafts fail because of necrosis or infection. Tissue engineering strategies seek to develop scaffolds that can regenerate injured muscles and restore functionality. Many of these scaffolds, however, are limited in their ability to restore muscle functionality because of an inability to promote the alignment of regenerating myofibers. For aligned myofibers to form on a scaffold, myoblasts infiltrate the scaffold and receive topographical cues to direct targeted myofiber growth. We seek to determine the optimal pore size for myoblast infiltration and differentiation. We developed a method of tuning the pore size within collagen scaffolds while inducing longitudinal alignment of these pores. Significantly different pore sizes were generated by adjusting the freezing rate of the scaffolds. Scaffolds frozen at -20 °C contained the largest pores. These scaffolds promoted the greatest level of cell infiltration and orientation in the direction of pore alignment. Further research will be conducted to induce higher levels of myofiber formation, to ultimately create an off-the-shelf treatment for VML injuries.
    Keywords:  biomaterial; collagen; pore size; porosity; scaffold; skeletal muscle; skeletal muscle tissue engineering; tissue engineering; volumetric muscle loss
    DOI:  https://doi.org/10.3390/jfb14110533
  2. Biomaterials. 2023 Nov 15. pii: S0142-9612(23)00410-6. [Epub ahead of print]303 122402
    Engineering large and geometrically controlled vascularized nerve tissue in collagen hydrogels to restore large-sized volumetric muscle loss.
    Shih-Yen Wei, Po-Yu Chen, Chia-Chang Hsieh, Yu-Shan Chen, Tzu-Hsuan Chen, Yu-Shan Yu, Min-Chun Tsai, Ren-Hao Xie, Guan-Yu Chen, Gung-Chian Yin, Juan M Melero-Martin, Ying-Chieh Chen.
      Developing scalable vascularized and innervated tissue is a critical challenge for the successful clinical application of tissue-engineered constructs. Collagen hydrogels are extensively utilized in cell-mediated vascular network formation because of their naturally excellent biological properties. However, the substantial increase in hydrogel contraction induced by populated cells limits their long-term use. Previous studies attempted to mitigate this issue by concentrating collagen pre-polymer solutions or synthesizing covalently crosslinked collagen hydrogels. However, these methods only partially reduce hydrogel contraction while hindering blood vessel formation within the hydrogels. To address this challenge, we introduced additional support in the form of a supportive spacer to counteract the contraction forces of populated cells and prevent hydrogel contraction. This approach was found to promote cell spreading, resist hydrogel contraction, control hydrogel/tissue geometry, and even facilitate the engineering of functional blood vessels and host nerve growth in just one week. Subsequently, implanting these engineered tissues into muscle defect sites resulted in timely anastomosis with the host vasculature, leading to enhanced myogenesis, increased muscle innervation, and the restoration of injured muscle functionality. Overall, this innovative strategy expands the applicability of collagen hydrogels in fabricating large vascularized nerve tissue constructs for repairing volumetric muscle loss (∼63 %) and restoring muscle function.
    Keywords:  Cell-populated hydrogel; Collagen hydrogel contraction; Muscle repair; Vascular tissue engineering; Volumetric muscle loss
    DOI:  https://doi.org/10.1016/j.biomaterials.2023.122402
  3. Biomedicines. 2023 Oct 27. pii: 2913. [Epub ahead of print]11(11):
    Chemical Transdifferentiation of Somatic Cells: Unleashing the Power of Small Molecules.
    Yu Zhang, Xuefeng Li, Jianyu Xing, Jinsong Zhou, Hai Li.
      Chemical transdifferentiation is a technique that utilizes small molecules to directly convert one cell type into another without passing through an intermediate stem cell state. This technique offers several advantages over other methods of cell reprogramming, such as simplicity, standardization, versatility, no ethical and safety concern and patient-specific therapies. Chemical transdifferentiation has been successfully applied to various cell types across different tissues and organs, and its potential applications are rapidly expanding as scientists continue to explore new combinations of small molecules and refine the mechanisms driving cell fate conversion. These applications have opened up new possibilities for regenerative medicine, disease modeling, drug discovery and tissue engineering. However, there are still challenges and limitations that need to be overcome before chemical transdifferentiation can be translated into clinical practice. These include low efficiency and reproducibility, incomplete understanding of the molecular mechanisms, long-term stability and functionality of the transdifferentiated cells, cell-type specificity and scalability. In this review, we compared the commonly used methods for cell transdifferentiation in recent years and discussed the current progress and future perspective of the chemical transdifferentiation of somatic cells and its potential impact on biomedicine. We believe that with ongoing research and technological advancements, the future holds tremendous promise for harnessing the power of small molecules to shape the cellular landscape and revolutionize the field of biomedicine.
    Keywords:  cell reprogramming; epithelial–mesenchymal transition; small molecule; transdifferentiation
    DOI:  https://doi.org/10.3390/biomedicines11112913
  4. Adv Healthc Mater. 2023 Nov 20. e2302180
    Biomimetic Conductive Hydrogel Scaffolds with Anisotropy And Electrical Stimulation for in Vivo Skeletal Muscle Reconstruction.
    Yan Xue, Jieling Li, Tianhe Jiang, Qingquan Han, Yafeng Jing, Shuo Bai, Xuehai Yan.
      The nature of the hydrogel scaffold mimicking extracellular matrix plays a crucial role in tissue engineering like skeletal muscle repair. Herein, an anisotropic and conductive hydrogel scaffold was fabricated using GelMA as the matrix hydrogel and AgNW as the conductive dopant, through a directional freezing technique for muscle defect repair. The scaffold has an anisotropic structure composed of a directional longitudinal section and a honeycomb cross-section, with high mechanical strength of 10.5 kPa and excellent conductivity of 0.26 S/m. These properties are similar to native muscle ECM and allow for cell orientation under the guidance of contact cues and electrical stimulation synergistically. In vitro experiments have shown that the scaffold's oriented structure combined with electrical stimulation results in enhanced myotube formation, with a length of up to 863 μm and an orientation rate of 81%. Furthermore, the electrically stimulated scaffold displays a promoted muscle reconstruction ability when transplanted into rats with muscle defects, achieving a muscle mass and strength restoration ratio of 95% and 99%, respectively, compared to normal levels. These findings suggest that the scaffold has great potential in muscle repair applications. This article is protected by copyright. All rights reserved.
    Keywords:  anisotropic hydrogel; biomimetic scaffold; cell alignment; electrical stimulation; skeletal muscle repair
    DOI:  https://doi.org/10.1002/adhm.202302180
  5. Biomaterials. 2023 Nov 11. pii: S0142-9612(23)00397-6. [Epub ahead of print]303 122389
    Atomic force microscopy-mediated mechanobiological profiling of complex human tissues.
    David H Cho, Sebastian Aguayo, Alexander X Cartagena-Rivera.
      Tissue mechanobiology is an emerging field with the overarching goal of understanding the interplay between biophysical and biochemical responses affecting development, physiology, and disease. Changes in mechanical properties including stiffness and viscosity have been shown to describe how cells and tissues respond to mechanical cues and modify critical biological functions. To quantitatively characterize the mechanical properties of tissues at physiologically relevant conditions, atomic force microscopy (AFM) has emerged as a highly versatile biomechanical technology. In this review, we describe the fundamental principles of AFM, typical AFM modalities used for tissue mechanics, and commonly used elastic and viscoelastic contact mechanics models to characterize complex human tissues. Furthermore, we discuss the application of AFM-based mechanobiology to characterize the mechanical responses within complex human tissues to track their developmental, physiological/functional, and diseased states, including oral, hearing, and cancer-related tissues. Finally, we discuss the current outlook and challenges to further advance the field of tissue mechanobiology. Altogether, AFM-based tissue mechanobiology provides a mechanistic understanding of biological processes governing the unique functions of tissues.
    DOI:  https://doi.org/10.1016/j.biomaterials.2023.122389
  6. Biochem Biophys Res Commun. 2023 Nov 17. pii: S0006-291X(23)01325-6. [Epub ahead of print]690 149231
    Development of a Cre-recombination-based color-switching reporter system for cell fusion detection.
    Toshifumi Asano, Philipp Sasse, Takao Nakata.
      Cell fusion plays a key role in the development and formation of tissues and organs in several organisms. Skeletal myogenesis is assessed in vitro by cell shape and gene and protein expression using immunofluorescence and immunoblotting assays. However, these conventional methods are complex and do not allow for easy time-course observation in living cells. Therefore, this study aimed to develop a Cre recombination-based fluorescent reporter system to monitor cell-cell fusion. We combined green and red fluorescent proteins with a Cre-loxP system to detect syncytium formation using a fluorescent binary switch. This allowed us to visualize mononucleated cells with green fluorescence before fusion and multinucleated syncytia with red fluorescence by conditional expression after cell fusion. The formation of multinuclear myotubes during myogenic differentiation was detected by the change in fluorescence from green to red after Cre-mediated recombination. The distribution of the fluorescence signal correlated with the expression of myogenic differentiation markers. Moreover, red reporter fluorescence intensity was correlated with the number of nuclei contained in the red fluorescent-positive myotubes. We also successfully demonstrated that our fusion monitoring system is applicable to the formation of skeletal muscle myotube and placental syncytiotrophoblast. These results suggest that the color-switching fluorescent reporter system, using Cre-mediated recombination, could be a robust tool used to facilitate the study of cell-to-cell fusion.
    Keywords:  Cell fusion; Cre-loxP; Fluorescent reporter; Multinuclear cell; Myoblast; Trophoblast
    DOI:  https://doi.org/10.1016/j.bbrc.2023.149231
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