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Moving toward Biomimetic Tissue Engineered Scaffolds

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A special issue of Nanomaterials (ISSN 2079-4991). This special issue belongs to the section "Biology and Medicines".

Deadline for manuscript submissions: closed (25 December 2023) | Viewed by 41290

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Special Issue Editors

Dr. Costantino Del Gaudio

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Guest Editor

Italian Space Agency, 00133 Rome, Italy
Interests: biomaterials; 3D printing; tissue engineering; nanomaterials; graphene; drug delivery systems; composites; microgravity

Dr. Silvia Baiguera

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Guest Editor

Department of Clinical Science and Translational Medicine, University of Rome “Tor Vergata”, Rome, Italy
Interests: tissue engineering; biomimetics; extracellular matrix; decellularization; growth factors

Prof. Dr. Lucy Di Silvio

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Guest Editor

Centre of Oral, Clinical & Translational Sciences, King’s College London, London, UK
Interests: tissue engineering; cellular/acellular scaffolds; stem cells; cell-material interactions

Special Issue Information

Dear Colleagues,

Tissue engineering can actually pave the way to the regeneration of damaged tissues, if driven by an accurate design approach to define instructive scaffolds. Innovative therapeutic solutions can be developed by synergistically combining synthetic or natural materials, fabrication techniques, cells, nanomaterials, and physicochemical surface functionalization. However, these general requirements have to be experimentally implemented, as the guiding role that a scaffold is expected to exert on cells needs to be finely tailored to provide a three-dimensional microenvironment that can functionally support biological processes. The goal to resemble the extracellular matrix (ECM) of the tissue to be healed is, therefore, the desired output for a correct physiological restoration without the drawbacks associated with conventional treatments. For this aim, biomimetics can provide pivotal cues to mimic a tissue-specific ECM, including morphological microarchitectures, selected biomaterials, nanofillers, and biochemical properties, to replicate the hierarchical structure and fabricate bioactive scaffolds for improved medical applications.

The proposed Special Issue aims to collect innovative contributions in the tissue engineering and regenerative-medicine fields, providing the state of the art and the foremost research findings on the design, realization, and modification strategies to fabricate advanced biomimetic scaffolds to promote tissue regeneration.

Original research and review articles are welcome; potential topics include, but are not limited to, the following:

Biomimetic scaffolds;
Additive manufacturing;
Combined scaffold fabrication techniques;
In vivo scaffold evaluation;
Scaffold nanostructuring and modification approaches;
Nanomaterials and their role;
Numerical simulations.

Dr. Costantino Del Gaudio
Dr. Silvia Baiguera
Prof. Dr. Lucy Di Silvio
Guest Editors

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Keywords

tissue-specific ECM scaffolds
3D printing
bioink formulation
in vivo cell-scaffold interaction
nanoparticles
biologically derived materials
4D materials
surface functionalization
bioreactors

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Published Papers (11 papers)

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Research

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18 pages, 5550 KiB

Open AccessArticle

In Vitro Modulation of Spontaneous Activity in Embryonic Cardiomyocytes Cultured on Poly(vinyl alcohol)/Bioglass Type 58S Electrospun Scaffolds

by Filiberto Rivera-Torres, Alfredo Maciel-Cerda, Gertrudis Hortensia González-Gómez, Alicia Falcón-Neri, Karla Gómez-Lizárraga, Héctor Tomás Esquivel-Posadas and Ricardo Vera-Graziano

Nanomaterials 2024, 14(4), 372; https://doi.org/10.3390/nano14040372 - 17 Feb 2024

Viewed by 1239

Abstract

Because of the physiological and cardiac changes associated with cardiovascular disease, tissue engineering can potentially restore the biological functions of cardiac tissue through the fabrication of scaffolds. In the present study, hybrid nanofiber scaffolds of poly (vinyl alcohol) (PVA) and bioglass type 58S (58SiO₂-33CaO-9P₂O₅, Bg) were fabricated, and their effect on the spontaneous activity of chick embryonic cardiomyocytes in vitro was determined. PVA/Bg nanofibers were produced by electrospinning and stabilized by chemical crosslinking with glutaraldehyde. The electrospun scaffolds were analyzed to determine their chemical structure, morphology, and thermal transitions. The crosslinked scaffolds were more stable to degradation in water. A Bg concentration of 25% in the hybrid scaffolds improved thermal stability and decreased degradation in water after PVA crosslinking. Cardiomyocytes showed increased adhesion and contractility in cells seeded on hybrid scaffolds with higher Bg concentrations. In addition, the effect of Ca²⁺ ions released from the bioglass on the contraction patterns of cultured cardiomyocytes was investigated. The results suggest that the scaffolds with 25% Bg led to a uniform beating frequency that resulted in synchronous contraction patterns. Full article

(This article belongs to the Special Issue Moving toward Biomimetic Tissue Engineered Scaffolds)

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16 pages, 6311 KiB

Open AccessArticle

The Effect of Substrate Properties on Cellular Behavior and Nanoparticle Uptake in Human Fibroblasts and Epithelial Cells

by Mauro Sousa de Almeida, Aaron Lee, Fabian Itel, Katharina Maniura-Weber, Alke Petri-Fink and Barbara Rothen-Rutishauser

Nanomaterials 2024, 14(4), 342; https://doi.org/10.3390/nano14040342 - 10 Feb 2024

Viewed by 1806

Abstract

The delivery of nanomedicines into cells holds enormous therapeutic potential; however little is known regarding how the extracellular matrix (ECM) can influence cell–nanoparticle (NP) interactions. Changes in ECM organization and composition occur in several pathophysiological states, including fibrosis and tumorigenesis, and may contribute to disease progression. We show that the physical characteristics of cellular substrates, that more closely resemble the ECM in vivo, can influence cell behavior and the subsequent uptake of NPs. Electrospinning was used to create two different substrates made of soft polyurethane (PU) with aligned and non-aligned nanofibers to recapitulate the ECM in two different states. To investigate the impact of cell–substrate interaction, A549 lung epithelial cells and MRC-5 lung fibroblasts were cultured on soft PU membranes with different alignments and compared against stiff tissue culture plastic (TCP)/glass. Both cell types could attach and grow on both PU membranes with no signs of cytotoxicity but with increased cytokine release compared with cells on the TCP. The uptake of silica NPs increased more than three-fold in fibroblasts but not in epithelial cells cultured on both membranes. This study demonstrates that cell–matrix interaction is substrate and cell-type dependent and highlights the importance of considering the ECM and tissue mechanical properties when designing NPs for effective cell targeting and treatment. Full article

(This article belongs to the Special Issue Moving toward Biomimetic Tissue Engineered Scaffolds)

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18 pages, 7027 KiB

Open AccessArticle

Hyaluronic Acid/Collagen Nanofiber Tubular Scaffolds Support Endothelial Cell Proliferation, Phenotypic Shape and Endothelialization

by Yuqing Niu and Massimiliano Galluzzi

Nanomaterials 2021, 11(9), 2334; https://doi.org/10.3390/nano11092334 - 8 Sep 2021

Cited by 20 | Viewed by 4127 | Correction

Abstract

In this study, we designed and synthetized artificial vascular scaffolds based on nanofibers of collagen functionalized with hyaluronic acid (HA) in order to direct the phenotypic shape, proliferation, and complete endothelization of mouse primary aortic endothelial cells (PAECs). Layered tubular HA/collagen nanofibers were prepared using electrospinning and crosslinking process. The obtained scaffold is composed of a thin inner layer and a thick outer layer that structurally mimic the layer the intima and media layers of the native blood vessels, respectively. Compared with the pure tubular collagen nanofibers, the surface of HA functionalized collagen nanofibers has higher anisotropic wettability and mechanical flexibility. HA/collagen nanofibers can significantly promote the elongation, proliferation and phenotypic shape expression of PAECs. In vitro co-culture of mouse PAECs and their corresponding smooth muscle cells (SMCs) showed that the luminal endothelialization governs the biophysical integrity of the newly formed extracellular matrix (e.g., collagen and elastin fibers) and structural remodeling of SMCs. Furthermore, in vitro hemocompatibility assays indicated that HA/collagen nanofibers have no detectable degree of hemolysis and coagulation, suggesting their promise as engineered vascular implants. Full article

(This article belongs to the Special Issue Moving toward Biomimetic Tissue Engineered Scaffolds)

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18 pages, 6159 KiB

Open AccessArticle

A Perfusion Bioreactor for Longitudinal Monitoring of Bioengineered Liver Constructs

by Lisa Sassi, Omolola Ajayi, Sara Campinoti, Dipa Natarajan, Claire McQuitty, Riccardo Rayan Siena, Sara Mantero, Paolo De Coppi, Alessandro F. Pellegata, Shilpa Chokshi and Luca Urbani

Nanomaterials 2021, 11(2), 275; https://doi.org/10.3390/nano11020275 - 21 Jan 2021

Cited by 17 | Viewed by 4431

Abstract

In the field of in vitro liver disease models, decellularised organ scaffolds maintain the original biomechanical and biological properties of the extracellular matrix and are established supports for in vitro cell culture. However, tissue engineering approaches based on whole organ decellularized scaffolds are hampered by the scarcity of appropriate bioreactors that provide controlled 3D culture conditions. Novel specific bioreactors are needed to support long-term culture of bioengineered constructs allowing non-invasive longitudinal monitoring. Here, we designed and validated a specific bioreactor for long-term 3D culture of whole liver constructs. Whole liver scaffolds were generated by perfusion decellularisation of rat livers. Scaffolds were seeded with Luc⁺HepG2 and primary human hepatocytes and cultured in static or dynamic conditions using the custom-made bioreactor. The bioreactor included a syringe pump, for continuous unidirectional flow, and a circuit built to allow non-invasive monitoring of culture parameters and media sampling. The bioreactor allowed non-invasive analysis of cell viability, distribution, and function of Luc⁺HepG2-bioengineered livers cultured for up to 11 days. Constructs cultured in dynamic conditions in the bioreactor showed significantly higher cell viability, measured with bioluminescence, distribution, and functionality (determined by albumin production and expression of CYP enzymes) in comparison to static culture conditions. Finally, our bioreactor supports primary human hepatocyte viability and function for up to 30 days, when seeded in the whole liver scaffolds. Overall, our novel bioreactor is capable of supporting cell survival and metabolism and is suitable for liver tissue engineering for the development of 3D liver disease models. Full article

(This article belongs to the Special Issue Moving toward Biomimetic Tissue Engineered Scaffolds)

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Review

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22 pages, 2207 KiB

Open AccessReview

Biomimetic Scaffolds—A Novel Approach to Three Dimensional Cell Culture Techniques for Potential Implementation in Tissue Engineering

by Tomasz Górnicki, Jakub Lambrinow, Afsaneh Golkar-Narenji, Krzysztof Data, Dominika Domagała, Julia Niebora, Maryam Farzaneh, Paul Mozdziak, Maciej Zabel, Paweł Antosik, Dorota Bukowska, Kornel Ratajczak, Marzenna Podhorska-Okołów, Piotr Dzięgiel and Bartosz Kempisty

Nanomaterials 2024, 14(6), 531; https://doi.org/10.3390/nano14060531 - 16 Mar 2024

Cited by 11 | Viewed by 3305

Abstract

Biomimetic scaffolds imitate native tissue and can take a multidimensional form. They are biocompatible and can influence cellular metabolism, making them attractive bioengineering platforms. The use of biomimetic scaffolds adds complexity to traditional cell cultivation methods. The most commonly used technique involves cultivating cells on a flat surface in a two-dimensional format due to its simplicity. A three-dimensional (3D) format can provide a microenvironment for surrounding cells. There are two main techniques for obtaining 3D structures based on the presence of scaffolding. Scaffold-free techniques consist of spheroid technologies. Meanwhile, scaffold techniques contain organoids and all constructs that use various types of scaffolds, ranging from decellularized extracellular matrix (dECM) through hydrogels that are one of the most extensively studied forms of potential scaffolds for 3D culture up to 4D bioprinted biomaterials. 3D bioprinting is one of the most important techniques used to create biomimetic scaffolds. The versatility of this technique allows the use of many different types of inks, mainly hydrogels, as well as cells and inorganic substances. Increasing amounts of data provide evidence of vast potential of biomimetic scaffolds usage in tissue engineering and personalized medicine, with the main area of potential application being the regeneration of skin and musculoskeletal systems. Recent papers also indicate increasing amounts of in vivo tests of products based on biomimetic scaffolds, which further strengthen the importance of this branch of tissue engineering and emphasize the need for extensive research to provide safe for humansbiomimetic tissues and organs. In this review article, we provide a review of the recent advancements in the field of biomimetic scaffolds preceded by an overview of cell culture technologies that led to the development of biomimetic scaffold techniques as the most complex type of cell culture. Full article

(This article belongs to the Special Issue Moving toward Biomimetic Tissue Engineered Scaffolds)

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22 pages, 2739 KiB

Open AccessReview

Challenges of Periodontal Tissue Engineering: Increasing Biomimicry through 3D Printing and Controlled Dynamic Environment

by Ilaria Roato, Beatrice Masante, Giovanni Putame, Diana Massai and Federico Mussano

Nanomaterials 2022, 12(21), 3878; https://doi.org/10.3390/nano12213878 - 2 Nov 2022

Cited by 15 | Viewed by 6304

Abstract

In recent years, tissue engineering studies have proposed several approaches to regenerate periodontium based on the use of three-dimensional (3D) tissue scaffolds alone or in association with periodontal ligament stem cells (PDLSCs). The rapid evolution of bioprinting has sped up classic regenerative medicine, making the fabrication of multilayered scaffolds—which are essential in targeting the periodontal ligament (PDL)—conceivable. Physiological mechanical loading is fundamental to generate this complex anatomical structure ex vivo. Indeed, loading induces the correct orientation of the fibers forming the PDL and maintains tissue homeostasis, whereas overloading or a failure to adapt to mechanical load can be at least in part responsible for a wrong tissue regeneration using PDLSCs. This review provides a brief overview of the most recent achievements in periodontal tissue engineering, with a particular focus on the use of PDLSCs, which are the best choice for regenerating PDL as well as alveolar bone and cementum. Different scaffolds associated with various manufacturing methods and data derived from the application of different mechanical loading protocols have been analyzed, demonstrating that periodontal tissue engineering represents a proof of concept with high potential for innovative therapies in the near future. Full article

(This article belongs to the Special Issue Moving toward Biomimetic Tissue Engineered Scaffolds)

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41 pages, 3802 KiB

Open AccessReview

Topography: A Biophysical Approach to Direct the Fate of Mesenchymal Stem Cells in Tissue Engineering Applications

by Xingli Cun and Leticia Hosta-Rigau

Nanomaterials 2020, 10(10), 2070; https://doi.org/10.3390/nano10102070 - 20 Oct 2020

Cited by 90 | Viewed by 5625

Abstract

Tissue engineering is a promising strategy to treat tissue and organ loss or damage caused by injury or disease. During the past two decades, mesenchymal stem cells (MSCs) have attracted a tremendous amount of interest in tissue engineering due to their multipotency and self-renewal ability. MSCs are also the most multipotent stem cells in the human adult body. However, the application of MSCs in tissue engineering is relatively limited because it is difficult to guide their differentiation toward a specific cell lineage by using traditional biochemical factors. Besides biochemical factors, the differentiation of MSCs also influenced by biophysical cues. To this end, much effort has been devoted to directing the cell lineage decisions of MSCs through adjusting the biophysical properties of biomaterials. The surface topography of the biomaterial-based scaffold can modulate the proliferation and differentiation of MSCs. Presently, the development of micro- and nano-fabrication techniques has made it possible to control the surface topography of the scaffold precisely. In this review, we highlight and discuss how the main topographical features (i.e., roughness, patterns, and porosity) are an efficient approach to control the fate of MSCs and the application of topography in tissue engineering. Full article

(This article belongs to the Special Issue Moving toward Biomimetic Tissue Engineered Scaffolds)

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13 pages, 1118 KiB

Open AccessReview

Harnessing Inorganic Nanoparticles to Direct Macrophage Polarization for Skeletal Muscle Regeneration

by Francesca Corsi, Felicia Carotenuto, Paolo Di Nardo and Laura Teodori

Nanomaterials 2020, 10(10), 1963; https://doi.org/10.3390/nano10101963 - 2 Oct 2020

Cited by 9 | Viewed by 3473

Abstract

Modulation of macrophage plasticity is emerging as a successful strategy in tissue engineering (TE) to control the immune response elicited by the implanted material. Indeed, one major determinant of success in regenerating tissues and organs is to achieve the correct balance between immune pro-inflammatory and pro-resolution players. In recent years, nanoparticle-mediated macrophage polarization towards the pro- or anti-inflammatory subtypes is gaining increasing interest in the biomedical field. In TE, despite significant progress in the use of nanomaterials, the full potential of nanoparticles as effective immunomodulators has not yet been completely realized. This work discusses the contribution that nanotechnology gives to TE applications, helping native or synthetic scaffolds to direct macrophage polarization; here, three bioactive metallic and ceramic nanoparticles (gold, titanium oxide, and cerium oxide nanoparticles) are proposed as potential valuable tools to trigger skeletal muscle regeneration. Full article

(This article belongs to the Special Issue Moving toward Biomimetic Tissue Engineered Scaffolds)

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19 pages, 1144 KiB

Open AccessReview

Smart ECM-Based Electrospun Biomaterials for Skeletal Muscle Regeneration

by Sara Politi, Felicia Carotenuto, Antonio Rinaldi, Paolo Di Nardo, Vittorio Manzari, Maria Cristina Albertini, Rodolfo Araneo, Seeram Ramakrishna and Laura Teodori

Nanomaterials 2020, 10(9), 1781; https://doi.org/10.3390/nano10091781 - 9 Sep 2020

Cited by 39 | Viewed by 6032

Abstract

The development of smart and intelligent regenerative biomaterials for skeletal muscle tissue engineering is an ongoing challenge, owing to the requirement of achieving biomimetic systems able to communicate biological signals and thus promote optimal tissue regeneration. Electrospinning is a well-known technique to produce fibers that mimic the three dimensional microstructural arrangements, down to nanoscale and the properties of the extracellular matrix fibers. Natural and synthetic polymers are used in the electrospinning process; moreover, a blend of them provides composite materials that have demonstrated the potential advantage of supporting cell function and adhesion. Recently, the decellularized extracellular matrix (dECM), which is the noncellular component of tissue that retains relevant biological cues for cells, has been evaluated as a starting biomaterial to realize composite electrospun constructs. The properties of the electrospun systems can be further improved with innovative procedures of functionalization with biomolecules. Among the various approaches, great attention is devoted to the “click” concept in constructing a bioactive system, due to the modularity, orthogonality, and simplicity features of the “click” reactions. In this paper, we first provide an overview of current approaches that can be used to obtain biofunctional composite electrospun biomaterials. Finally, we propose a design of composite electrospun biomaterials suitable for skeletal muscle tissue regeneration. Full article

(This article belongs to the Special Issue Moving toward Biomimetic Tissue Engineered Scaffolds)

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Other

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3 pages, 2608 KiB

Open AccessCorrection

Correction: Niu, Y.; Galluzzi, M. Hyaluronic Acid/Collagen Nanofiber Tubular Scaffolds Support Endothelial Cell Proliferation, Phenotypic Shape and Endothelialization. Nanomaterials 2021, 11, 2334

by Yuqing Niu and Massimiliano Galluzzi

Nanomaterials 2024, 14(14), 1203; https://doi.org/10.3390/nano14141203 - 16 Jul 2024

Viewed by 480

Abstract

In the original publication [...] Full article

(This article belongs to the Special Issue Moving toward Biomimetic Tissue Engineered Scaffolds)

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9 pages, 498 KiB

Open AccessPerspective

Information-Driven Design as a Potential Approach for 3D Printing of Skeletal Muscle Biomimetic Scaffolds

by Silvia Baiguera, Costantino Del Gaudio, Felicia Carotenuto, Paolo Di Nardo and Laura Teodori

Nanomaterials 2020, 10(10), 1986; https://doi.org/10.3390/nano10101986 - 8 Oct 2020

Cited by 3 | Viewed by 2670

Abstract

Severe muscle injuries are a real clinical issue that still needs to be successfully addressed. Tissue engineering can represent a potential approach for this aim, but effective healing solutions have not been developed yet. In this regard, novel experimental protocols tailored to a biomimetic approach can thus be defined by properly systematizing the findings acquired so far in the biomaterials and scaffold manufacturing fields. In order to plan a more comprehensive strategy, the extracellular matrix (ECM), with its properties stimulating neomyogenesis and vascularization, should be considered as a valuable biomaterial to be used to fabricate the tissue-specific three-dimensional structure of interest. The skeletal muscle decellularized ECM can be processed and printed, e.g., by means of stereolithography, to prepare bioactive and biomimetic 3D scaffolds, including both biochemical and topographical features specifically oriented to skeletal muscle regenerative applications. This paper aims to focus on the skeletal muscle tissue engineering sector, suggesting a possible approach to develop instructive scaffolds for a guided healing process. Full article

(This article belongs to the Special Issue Moving toward Biomimetic Tissue Engineered Scaffolds)

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