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Biomedicines
Special Issues
Engineering 3D Tissue Models: Techniques and Applications in Regenerative Medicine
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Engineering 3D Tissue Models: Techniques and Applications in Regenerative Medicine

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: 31 March 2025 | Viewed by 2099

Special Issue Editor

Dr. Agnes Klar

E-Mail Website
Guest Editor
Tissue Biology Research Unit, Department of Surgery, University Children’s Hospital Zurich, 8032 Zurich, Switzerland
Interests: human skin; keratinocytes; endothelial cells; skin substitutes; stem cells; melanocytes; adipose-dervied stem cells; fat tissue; skin inflammation; immune cells; skin adipocyte progenitors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Animal experimentation has long been used in science to study complex biological phenomena that cannot be studied using two-dimensional in vitro models. With time, it emerged that animal models do not fully resemble the real (patho-) physiological tissue environment, in particular when translated to human patients. Recently, 3D cell culture systems have been improved with new techniques and formulations that allow the culture of cell lines as well as organoids from primary tissues. In these conditions, tissue-engineered micro-tissues can orient themselves spatially, creating niches enriched in stem or differentiated cells specific to the tissue of origin. These tools allow precise and direct monitoring of physiological and pathological mechanisms and are often much more informative and versatile than in vivo tests. Thus, three-dimensional cell culture represents an excellent alternative to the animal model by mimicking the in vivo microenvironment. These innovative in vitro models can recapitulate the complexity of the tissue of origin, with different cellular components (epithelium, stroma, leukocytes) colonizing a matrix that reproduces the spatial conformation of the tissue vitro by mimicking the in vivo microenvironment without the use of animal models that are usually quite expensive and, in some instances, do not fully resemble the real pathophysiological environment. These tools can be essential for analyzing the physiological behavior of healthy cells and patient cells derived from several diseases such as cancers, metabolic diseases, neurodegenerative disorders, autoimmune diseases, and inherited pathologies allowing for a more accurate personalized medicine approach.

Dr. Agnes Klar
Guest Editor

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Keywords

  • application of organoids
  • self-assembly method
  • dynamic perfusion bioreactor approach for tissue engineering
  • magnetic levitation
  • microfluidic 3D cell culture
  • body-on-a-chip
  • adipocyte in vitro platform to model metabolic diseases
  • skin irritation models
  • vascular blood-brain barrier in vitro
  • iPSC-derived models of healthy and diseased tissues
  • personalized medicine
  • integrated 3D cell culture models for preclinical drug development

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Published Papers (2 papers)

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Research

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13 pages, 6167 KiB  
Article
Collagen I Microfiber Promotes Brain Capillary Network Formation in Three–Dimensional Blood–Brain Barrier Microphysiological Systems
by Kimiko Nakayama-Kitamura, Yukari Shigemoto-Mogami, Marie Piantino, Yasuhiro Naka, Asuka Yamada, Shiro Kitano, Tomomi Furihata, Michiya Matsusaki and Kaoru Sato
Biomedicines 2024, 12(11), 2500; https://doi.org/10.3390/biomedicines12112500 - 31 Oct 2024
Cited by 1 | Viewed by 1247
Abstract
Background: The blood–brain barrier (BBB) strictly regulates the penetration of substances into the brain, which, although important for maintaining brain homeostasis, may delay drug development because of the difficulties in predicting pharmacokinetics/pharmacodynamics (PKPD), toxicokinetics/toxicodynamics (TKTD), toxicity, safety, and efficacy in the central nervous [...] Read more.
Background: The blood–brain barrier (BBB) strictly regulates the penetration of substances into the brain, which, although important for maintaining brain homeostasis, may delay drug development because of the difficulties in predicting pharmacokinetics/pharmacodynamics (PKPD), toxicokinetics/toxicodynamics (TKTD), toxicity, safety, and efficacy in the central nervous system (CNS). Moreover, BBB functional proteins show species differences; therefore, humanized in vitro BBB models are urgently needed to improve the predictability of preclinical studies. Recently, international trends in the 3Rs in animal experiments and the approval of the FDA Modernization Act 2.0 have accelerated the application of microphysiological systems (MPSs) in preclinical studies, and in vitro BBB models have become synonymous with BBB–MPSs. Recently, we developed an industrialized humanized BBB–MPS, BBB–NET. In our previous report, we reproduced transferrin receptor (TfR)–mediated transcytosis with high efficiency and robustness, using hydrogels including fibrin and collagen I microfibers (CMFs). Methods: We investigated how adding CMFs to the fibrin gel benefits BBB-NETs. Results: We showed that CMFs accelerate capillary network formation and maturation by promoting astrocyte (AC) survival, and clarified that integrin β1 is involved in the mechanism of CMFs. Conclusions: Our data suggest that the quality control (QC) of CMFs is important for ensuring the stable production of BBB–NETs. Full article
(This article belongs to the Special Issue Engineering 3D Tissue Models: Techniques and Applications in Regenerative Medicine)
►▼ Show Figures

Figure 1

Figure 1
<p>CMFs are important for the autonomous production of capillary networks. (<b>A</b>) Schematic of the BBB–NET components. (<b>B</b>) Representative z–stack images of the endothelial cell markers CD31 (<b>a</b>,<b>b</b>) and CD146 (<b>d</b>,<b>e</b>) and the basement membrane protein collagen IV (<b>g</b>,<b>h</b>) in hydrogels with (<b>b</b>,<b>e</b>,<b>h</b>) and without (<b>a</b>,<b>d</b>,<b>g</b>) CMFs. Scale bar: 100 μm. Comparison of the capillary volumes positive for CD31 (<b>c</b>), CD146 (<b>f</b>), and collagen IV (<b>i</b>) among hydrogels with and without CMFs. The percentage of positive staining in the presence of CMFs is shown, and without CMFs it was taken to be 100%. All data are expressed as the means ± standard errors of the means (SEMs). Each representation shown is from three independent experiments, each with four images. Student’s <span class="html-italic">t</span> test, *: <span class="html-italic">p</span> &lt; 0.05, **: <span class="html-italic">p</span> &lt; 0.01.</p> Full article ">Figure 2
<p>CMFs support astrocyte survival. (<b>A</b>) Representative z-stack images of the astrocyte marker aquaporin 4 (<b>a</b>–<b>c</b>) and Cell Tracker-labelled astrocytes (<b>d</b>,<b>e</b>) in hydrogels with (<b>b</b>,<b>c</b>,<b>e</b>) and without (<b>a</b>,<b>d</b>) CMFs. Arrows in (<b>c</b>) show AQP4–positive ACs surrounded CD31-positive capillaries. Scale bar in (<b>a</b>,<b>b</b>,<b>d</b>,<b>e</b>): 100 μm; scale bar in (<b>c</b>): 50 μm. (<b>B</b>) Schematic of the astrocyte−only gel (<b>a</b>). Representative z−stack images of Cell Tracker−labelled astrocytes in hydrogels with (<b>c</b>) and without (<b>b</b>) CMFs. Comparison of the number of astrocytes in hydrogels with and without CMFs (<b>d</b>). Each representation shown is from three independent experiments, each with four images. Student’s <span class="html-italic">t</span> test, *: <span class="html-italic">p</span> &lt; 0.05. Scale bar in (<b>b</b>,<b>c</b>): 100 μm.</p> Full article ">Figure 3
<p>Astrocytes promote the formation and maturation of capillary networks. (<b>A</b>) Schematic of hydrogels with CMFs and with (<b>a</b>) and without (<b>b</b>) ACs. (<b>B</b>) Representative z–stack images of CD31 (<b>c</b>,<b>d</b>) and collagen IV (<b>f</b>,<b>g</b>) in the presence (<b>c</b>,<b>f</b>) and absence (<b>d</b>,<b>g</b>) of astrocytes in the hydrogel with CMFs. Scale bar: 100 μm. Comparison of CD31–positive capillary volume (<b>e</b>) and collagen IV–positive blood vessels (<b>h</b>) in the absence and presence of astrocytes in the hydrogel with CMFs. Each representation shown is from three independent experiments, each with four images. Student’s <span class="html-italic">t</span> test, *: <span class="html-italic">p</span> &lt; 0.05; **: <span class="html-italic">p</span> &lt; 0.01.</p> Full article ">Figure 4
<p>CMFs interact with astrocytes via the integrin β1 subunit. (<b>A</b>) Schematic of AC pretreated with and without each antibody in hydrogels with (<b>a</b>) and without CMF (<b>b</b>). (<b>B</b>) Comparison of the number of astrocytes after pretreatment with an integrin β1 antibody or an isotype control in hydrogels with CMFs. Each representation shown is from three independent experiments, each with four images. Student’s <span class="html-italic">t</span> test, *: <span class="html-italic">p</span> &lt; 0.05. (<b>C</b>) Comparison of the number of astrocytes after pretreatment with an integrin β1 antibody or an isotype control in hydrogels without CMFs. Each representation shown is from two independent experiments, each with four images.</p> Full article ">Figure 5
<p>Our hypothesized mechanism by which CMFs promote capillary formation and maturation in BBB-NETs. CMFs increased the number of surviving ACs by interacting with integrin β1, and the increased number of ACs supported capillary formation and maturation.</p> Full article ">

Other

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22 pages, 872 KiB  
Systematic Review
Update on the Study of Angiogenesis in Surgical Wounds in Patients with Childhood Obesity
by Cristina Chelmu Voda, Ioana Anca Stefanopol, Gabriela Gurau, Maria Andrada Hîncu, Gabriel Valeriu Popa, Olivia Garofita Mateescu, Liliana Baroiu and Mihaela Cezarina Mehedinti
Biomedicines 2025, 13(2), 375; https://doi.org/10.3390/biomedicines13020375 - 5 Feb 2025
Viewed by 490
Abstract
Background: Angiogenesis, the formation of new blood vessels from pre-existing ones, plays a pivotal role in wound healing, particularly in surgical contexts. Methods and results: However, this process can be significantly impaired in patients with childhood obesity, resulting in delayed healing and additional [...] Read more.
Background: Angiogenesis, the formation of new blood vessels from pre-existing ones, plays a pivotal role in wound healing, particularly in surgical contexts. Methods and results: However, this process can be significantly impaired in patients with childhood obesity, resulting in delayed healing and additional complications. The biological process of wound healing is complex, involving angiogenesis, cell proliferation, inflammation, and tissue remodeling. This review aims to explore recent advancements in research on angiogenesis in surgical wounds in patients with childhood obesity, with a focus on growth factors, inflammation, microcirculation, and innovative therapeutic strategies. Conclusions: It highlights therapeutic approaches such as the administration of growth factors and the application of biomaterials to enhance angiogenesis. Full article
(This article belongs to the Special Issue Engineering 3D Tissue Models: Techniques and Applications in Regenerative Medicine)
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Figure 1

Figure 1
<p>Prisma flow chart; this diagram shows the systematic process we followed to include the works captured by our search.</p> Full article ">Figure 2
<p>Comparison of healing aspects in normal-weight versus obese pediatric patients. The graph displays several key parameters of wound healing.</p> Full article ">Figure 3
<p>A comparison of healing characteristics by location, size, and depth in pediatric patients. This figure illustrates the healing efficiency (expressed as a percentage) in pediatric patients categorized by normal weight (blue bars) and obesity (orange bars). The analysis considers three wound characteristics: location, size, and depth. Healing locations include wounds on the upper limbs, lower limbs, and abdomen. Wound size is divided into small, moderate, and large wounds, while depth is categorized as shallow, moderate, and deep.</p> Full article ">
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