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Micro-Scale Approaches in Regenerative Medicine and Tissue Engineering 2023
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Micro-Scale Approaches in Regenerative Medicine and Tissue Engineering 2023

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Materials Science".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 23606

Special Issue Editors

Prof. Dr. Valeria Chiono

E-Mail Website
Guest Editor
1. Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Corso Duca Degli Abruzzi 24, 10129 Turin, Italy
2. Interuniversity Center for the Promotion of 3Rs Principle in Teaching and Research, Centro 3R, 56122 Pisa, Italy
Interests: tissue engineering; scaffold; hydrogels; drug release
Special Issues, Collections and Topics in MDPI journals
Dr. Irene Carmagnola

E-Mail Website
Guest Editor
1. Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Corso Duca Degli Abruzzi 24, 10129 Turin, Italy
2. Interuniversity Center for the Promotion of 3Rs Principle in Teaching and Research, Centro 3R, 56122 Pisa, Italy
Interests: hydrogels; coatings; surface functionalization; tissue engineering
Special Issues, Collections and Topics in MDPI journals
Dr. Alice Zoso

E-Mail Website
Guest Editor
1. Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Corso Duca Degli Abruzzi 24, 10129 Turin, Italy
2. Interuniversity Center for the Promotion of 3Rs Principle in Teaching and Research, Centro 3R, 56122 Pisa, Italy
Interests: tissue engineering; in vitro validation; 3D models
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The field of tissue engineering and regenerative medicine (TERM) has dramatically advanced in the last 20 years, providing the potential for regenerating almost every tissue and organ of the human body. TERM aims at the design of functional three-dimensional constructs able to properly guide cell behavior for tissue/organ regeneration or modeling.

Human tissues are complex systems comprising cells subjected to multiple and dynamic stimuli that change in time and space. Typical signals are direct cell–cell contacts, gradients of cytokines and secreted proteins from neighboring cells, and biochemical and mechanical interactions with the extracellular matrix (ECM). Different organs and tissues are characterized by a hierarchical structure with a complex organization of these elements, giving rise to unique arrangements.

TERM has taken the advantage of an interdisciplinary approach, involving aspects of cell biology, biomaterials science, surface functionalization and characterization, and cell–material interactions often integrated into microfabricated systems to accurately reproduce the complexity of in vivo microenvironments, including ECM organization and other tissue features (e.g., electrical stimuli, mechanical stress). The microscale design of cell culture environments has the potential to allow controllable and reproducible cell organization following tissue-specific cues.

The topics to be covered in this issue include advanced microtechnologies applied to the TERM field, such as the following:

  • Microhydrogels.
  • Microfluidic systems.
  • Microcontrolled surface and interface patterns.
  • Microbioreactors.
  • Microfabrication of 2D and 3D scaffolds.
  • Microcarriers for drug release.
  • Microsystems for cell adhesion.
  • Single-cell stimulation.
  • Cell microenvironments.

Prof. Dr. Valeria Chiono
Dr. Irene Carmagnola
Dr. Alice Zoso
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • microscale
  • scaffold
  • TERM
  • surface characterization
  • hydrogel
  • drug release
  • biomimetics

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Published Papers (6 papers)

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Research

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19 pages, 3075 KiB  
Article
Engineering a 3D In Vitro Model of Human Gingival Tissue Equivalent with Genipin/Cytochalasin D
by Cecilia Koskinen Holm and Chengjuan Qu
Int. J. Mol. Sci. 2022, 23(13), 7401; https://doi.org/10.3390/ijms23137401 - 3 Jul 2022
Cited by 6 | Viewed by 2848
Abstract
Although three-dimensional (3D) co-culture of gingival keratinocytes and fibroblasts-populated collagen gel can mimic 3D structure of in vivo tissue, the uncontrolled contraction of collagen gel restricts its application in clinical and experimental practices. We here established a stable 3D gingival tissue equivalent (GTE) [...] Read more.
Although three-dimensional (3D) co-culture of gingival keratinocytes and fibroblasts-populated collagen gel can mimic 3D structure of in vivo tissue, the uncontrolled contraction of collagen gel restricts its application in clinical and experimental practices. We here established a stable 3D gingival tissue equivalent (GTE) using hTERT-immortalized gingival fibroblasts (hGFBs)-populated collagen gel directly crosslinked with genipin/cytochalasin D and seeding hTERT-immortalized gingival keratinocytes (TIGKs) on the upper surface for a 2-week air–liquid interface co-culture. MTT assay was used to measure the cell viability of GTEs. GTE size was monitored following culture period, and the contraction was analyzed. Immunohistochemical assay was used to analyze GTE structure. qRT-PCR was conducted to examine the mRNA expression of keratinocyte-specific genes. Fifty µM genipin (G50) or combination (G + C) of G50 and 100 nM cytochalasin D significantly inhibited GTE contraction. Additionally, a higher cell viability appeared in GTEs crosslinked with G50 or G + C. GTEs crosslinked with genipin/cytochalasin D showed a distinct multilayered stratified epithelium that expressed keratinocyte-specific genes similar to native gingiva. Collagen directly crosslinked with G50 or G + C significantly reduced GTE contraction without damaging the epithelium. In summary, the TIGKs and hGFBs can successfully form organotypic multilayered cultures, which can be a valuable tool in the research regarding periodontal disease as well as oral mucosa disease. We conclude that genipin is a promising crosslinker with the ability to reduce collagen contraction while maintaining normal cell function in collagen-based oral tissue engineering. Full article
(This article belongs to the Special Issue Micro-Scale Approaches in Regenerative Medicine and Tissue Engineering 2023)
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22 pages, 3321 KiB  
Article
Electrical Stimulation Increases Axonal Growth from Dorsal Root Ganglia Co-Cultured with Schwann Cells in Highly Aligned PLA-PPy-Au Microfiber Substrates
by Fernando Gisbert Roca, Sara Serrano Requena, Manuel Monleón Pradas and Cristina Martínez-Ramos
Int. J. Mol. Sci. 2022, 23(12), 6362; https://doi.org/10.3390/ijms23126362 - 7 Jun 2022
Cited by 10 | Viewed by 2389
Abstract
Nerve regeneration is a slow process that needs to be guided for distances greater than 5 mm. For this reason, different strategies are being studied to guide axonal growth and accelerate the axonal growth rate. In this study, we employ an electroconductive fibrillar [...] Read more.
Nerve regeneration is a slow process that needs to be guided for distances greater than 5 mm. For this reason, different strategies are being studied to guide axonal growth and accelerate the axonal growth rate. In this study, we employ an electroconductive fibrillar substrate that is able to topographically guide axonal growth while accelerating the axonal growth rate when subjected to an exogenous electric field. Dorsal root ganglia were seeded in co-culture with Schwann cells on a substrate of polylactic acid microfibers coated with the electroconductive polymer polypyrrole, adding gold microfibers to increase its electrical conductivity. The substrate is capable of guiding axonal growth in a highly aligned manner and, when subjected to an electrical stimulation, an improvement in axonal growth is observed. As a result, an increase in the maximum length of the axons of 19.2% and an increase in the area occupied by the axons of 40% were obtained. In addition, an upregulation of the genes related to axon guidance, axogenesis, Schwann cells, proliferation and neurotrophins was observed for the electrically stimulated group. Therefore, our device is a good candidate for nerve regeneration therapies. Full article
(This article belongs to the Special Issue Micro-Scale Approaches in Regenerative Medicine and Tissue Engineering 2023)
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11 pages, 2153 KiB  
Article
Strontium Peroxide-Loaded Composite Scaffolds Capable of Generating Oxygen and Modulating Behaviors of Osteoblasts and Osteoclasts
by Sheng-Ju Lin and Chieh-Cheng Huang
Int. J. Mol. Sci. 2022, 23(11), 6322; https://doi.org/10.3390/ijms23116322 - 5 Jun 2022
Cited by 15 | Viewed by 2558
Abstract
The reconstruction of bone defects remains challenging. The utilization of bone autografts, although quite promising, is limited by several drawbacks, especially substantial donor site complications. Recently, strontium (Sr), a bioactive trace element with excellent osteoinductive, osteoconductive, and pro-angiogenic properties, has emerged as a [...] Read more.
The reconstruction of bone defects remains challenging. The utilization of bone autografts, although quite promising, is limited by several drawbacks, especially substantial donor site complications. Recently, strontium (Sr), a bioactive trace element with excellent osteoinductive, osteoconductive, and pro-angiogenic properties, has emerged as a potential therapeutic agent for bone repair. Herein, a strontium peroxide (SrO2)-loaded poly(lactic-co-glycolic acid) (PLGA)-gelatin scaffold system was developed as an implantable bone substitute. Gelatin sponges serve as porous osteoconductive scaffolds, while PLGA not only reinforces the mechanical strength of the gelatin but also controls the rate of water infiltration. The encapsulated SrO2 can release Sr2+ in a sustained manner upon exposure to water, thus effectively stimulating the proliferation of osteoblasts and suppressing the formation of osteoclasts. Moreover, SrO2 can generate hydrogen peroxide and subsequent oxygen molecules to increase local oxygen tension, an essential niche factor for osteogenesis. Collectively, the developed SrO2-loaded composite scaffold shows promise as a multifunctional bioactive bone graft for bone tissue engineering. Full article
(This article belongs to the Special Issue Micro-Scale Approaches in Regenerative Medicine and Tissue Engineering 2023)
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Review

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27 pages, 1760 KiB  
Review
Biomaterials-Enhanced Intranasal Delivery of Drugs as a Direct Route for Brain Targeting
by Elena Marcello and Valeria Chiono
Int. J. Mol. Sci. 2023, 24(4), 3390; https://doi.org/10.3390/ijms24043390 - 8 Feb 2023
Cited by 14 | Viewed by 7627
Abstract
Intranasal (IN) drug delivery is a non-invasive and effective route for the administration of drugs to the brain at pharmacologically relevant concentrations, bypassing the blood–brain barrier (BBB) and minimizing adverse side effects. IN drug delivery can be particularly promising for the treatment of [...] Read more.
Intranasal (IN) drug delivery is a non-invasive and effective route for the administration of drugs to the brain at pharmacologically relevant concentrations, bypassing the blood–brain barrier (BBB) and minimizing adverse side effects. IN drug delivery can be particularly promising for the treatment of neurodegenerative diseases. The drug delivery mechanism involves the initial drug penetration through the nasal epithelial barrier, followed by drug diffusion in the perivascular or perineural spaces along the olfactory or trigeminal nerves, and final extracellular diffusion throughout the brain. A part of the drug may be lost by drainage through the lymphatic system, while a part may even enter the systemic circulation and reach the brain by crossing the BBB. Alternatively, drugs can be directly transported to the brain by axons of the olfactory nerve. To improve the effectiveness of drug delivery to the brain by the IN route, various types of nanocarriers and hydrogels and their combinations have been proposed. This review paper analyzes the main biomaterials-based strategies to enhance IN drug delivery to the brain, outlining unsolved challenges and proposing ways to address them. Full article
(This article belongs to the Special Issue Micro-Scale Approaches in Regenerative Medicine and Tissue Engineering 2023)
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38 pages, 8333 KiB  
Review
Multifunctional Scaffolds Based on Emulsion and Coaxial Electrospinning Incorporation of Hydroxyapatite for Bone Tissue Regeneration
by Amirmajid Kadkhodaie Elyaderani, María del Carmen De Lama-Odría, Luis J. del Valle and Jordi Puiggalí
Int. J. Mol. Sci. 2022, 23(23), 15016; https://doi.org/10.3390/ijms232315016 - 30 Nov 2022
Cited by 16 | Viewed by 3768
Abstract
Tissue engineering is nowadays a powerful tool to restore damaged tissues and recover their normal functionality. Advantages over other current methods are well established, although a continuous evolution is still necessary to improve the final performance and the range of applications. Trends are [...] Read more.
Tissue engineering is nowadays a powerful tool to restore damaged tissues and recover their normal functionality. Advantages over other current methods are well established, although a continuous evolution is still necessary to improve the final performance and the range of applications. Trends are nowadays focused on the development of multifunctional scaffolds with hierarchical structures and the capability to render a sustained delivery of bioactive molecules under an appropriate stimulus. Nanocomposites incorporating hydroxyapatite nanoparticles (HAp NPs) have a predominant role in bone tissue regeneration due to their high capacity to enhance osteoinduction, osteoconduction, and osteointegration, as well as their encapsulation efficiency and protection capability of bioactive agents. Selection of appropriated polymeric matrices is fundamental and consequently great efforts have been invested to increase the range of properties of available materials through copolymerization, blending, or combining structures constituted by different materials. Scaffolds can be obtained from different processes that differ in characteristics, such as texture or porosity. Probably, electrospinning has the greater relevance, since the obtained nanofiber membranes have a great similarity with the extracellular matrix and, in addition, they can easily incorporate functional and bioactive compounds. Coaxial and emulsion electrospinning processes appear ideal to generate complex systems able to incorporate highly different agents. The present review is mainly focused on the recent works performed with Hap-loaded scaffolds having at least one structural layer composed of core/shell nanofibers. Full article
(This article belongs to the Special Issue Micro-Scale Approaches in Regenerative Medicine and Tissue Engineering 2023)
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26 pages, 405 KiB  
Review
Tissue Engineering and Regenerative Medicine in Pediatric Urology: Urethral and Urinary Bladder Reconstruction
by Martina Casarin, Alessandro Morlacco and Fabrizio Dal Moro
Int. J. Mol. Sci. 2022, 23(12), 6360; https://doi.org/10.3390/ijms23126360 - 7 Jun 2022
Cited by 20 | Viewed by 3621
Abstract
In the case of pediatric urology there are several congenital conditions, such as hypospadias and neurogenic bladder, which affect, respectively, the urethra and the urinary bladder. In fact, the gold standard consists of a urethroplasty procedure in the case of urethral malformations and [...] Read more.
In the case of pediatric urology there are several congenital conditions, such as hypospadias and neurogenic bladder, which affect, respectively, the urethra and the urinary bladder. In fact, the gold standard consists of a urethroplasty procedure in the case of urethral malformations and enterocystoplasty in the case of urinary bladder disorders. However, both surgical procedures are associated with severe complications, such as fistulas, urethral strictures, and dehiscence of the repair or recurrence of chordee in the case of urethroplasty, and metabolic disturbances, stone formation, urine leakage, and chronic infections in the case of enterocystoplasty. With the aim of overcoming the issue related to the lack of sufficient and appropriate autologous tissue, increasing attention has been focused on tissue engineering. In this review, both the urethral and the urinary bladder reconstruction strategies were summarized, focusing on pediatric applications and evaluating all the biomaterials tested in both animal models and patients. Particular attention was paid to the capability for tissue regeneration in dependence on the eventual presence of seeded cell and growth factor combinations in several types of scaffolds. Moreover, the main critical features needed for urinary tissue engineering have been highlighted and specifically focused on for pediatric application. Full article
(This article belongs to the Special Issue Micro-Scale Approaches in Regenerative Medicine and Tissue Engineering 2023)
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