Multifunctional Bio-Scaffolds for Cell Growth and Tissue Morphogenesis

A special issue of Journal of Functional Biomaterials (ISSN 2079-4983). This special issue belongs to the section "Biomaterials for Tissue Engineering and Regenerative Medicine".

Deadline for manuscript submissions: closed (20 November 2024) | Viewed by 19337

Special Issue Editors


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Guest Editor
Independent Researcher, Barcelona, Spain
Interests: biomaterials; biomedical engineering; cell culture; CAD/CAM; drug delivery; scaffolds

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Guest Editor
Institute of Polymers, Composites and Biomaterials, National Research Council, 80125 Naples, Italy
Interests: biomaterials; 3D printing; multifunctional scaffolds; biomimetic design
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), IDIS Research Institute, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
Interests: biomaterials; regenerative medicine; drug delivery; hydrogels; scaffolds; nanotechnology

Special Issue Information

Dear Colleagues,

Advanced tissue engineering strategies aim to restore the functionalities of damaged and/or dysfunctional tissues and organs by the sapient combination and integration of biomaterials, cells, and bioactive molecules. The synergy and interplay among these three elements contribute to the truthful formation of mechanically stable and biochemically functional biodegradable and bioactive scaffolds (bio-scaffolds) toward new tissue growth and morphogenesis. Traditionally, bioscaffolds can be obtained via cell transplantation into the pores of a three-dimensionally porous monolith. More recently, computer-aided design and manufacturing (CAD-CAM) processes, such as bioprinting and VAT polymerization, have emerged as a promising strategy to simultaneously process biomaterials, cells, and bioactive molecules to obtain bioscaffolds following tissue- and patient-specific biomimetic designs. The aim of this Special Issue is to collect articles presenting state-of-the-art knowledge on bioscaffold design, processing, and validation as shared by experts in these research fields. Special emphasis will be devoted to cutting-edge research regarding technological advancements of (i) biomaterial (e.g., biodegradable polyesters and hydrogels) design and processing with micro- and nanometric scale control of biochemical and architectural properties; (ii) bioactive molecule (e.g., growth factor) loading and release from bioscaffolds; (iii) cell behavior and tissue morphogenesis within bioscaffolds.

Dr. Aurelio Salerno
Dr. Alfredo Ronca
Dr. Anna Abbadessa
Guest Editors

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Keywords

  • additive manufacturing
  • biomimetic design
  • CAD-CAM
  • drug delivery
  • porous scaffolds
  • tissue morphogenesis

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Published Papers (8 papers)

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Research

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15 pages, 3657 KiB  
Article
Photochemical Modification of the Extracellular Matrix to Alter the Vascular Remodeling Process
by Blake Anderson, Dylan Blair, Kenji Huff, John Wisniewski, Kevin S. Warner and Katalin Kauser
J. Funct. Biomater. 2023, 14(12), 566; https://doi.org/10.3390/jfb14120566 - 15 Dec 2023
Viewed by 1826
Abstract
Therapeutic interventions for vascular diseases aim at achieving long-term patency by controlling vascular remodeling. The extracellular matrix (ECM) of the vessel wall plays a crucial role in regulating this process. This study introduces a novel photochemical treatment known as Natural Vascular Scaffolding, utilizing [...] Read more.
Therapeutic interventions for vascular diseases aim at achieving long-term patency by controlling vascular remodeling. The extracellular matrix (ECM) of the vessel wall plays a crucial role in regulating this process. This study introduces a novel photochemical treatment known as Natural Vascular Scaffolding, utilizing a 4-amino substituted 1,8-naphthimide (10-8-10 Dimer) and 450 nm light. This treatment induces structural changes in the ECM by forming covalent bonds between amino acids in ECM fibers without harming vascular cell survival, as evidenced by our results. To further investigate the mechanism of this treatment, porcine carotid artery segments were exposed to 10-8-10 Dimer and light activation. Subsequent experiments subjected these segments to enzymatic degradation through elastase or collagenase treatment and were analyzed using digital image analysis software (MIPAR) after histological processing. The results demonstrated significant preservation of collagen and elastin structures in the photochemically treated vascular wall, compared to controls. This suggests that photochemical treatment can effectively modulate vascular remodeling by enhancing the resistance of the ECM scaffold to degradation. This approach shows promise in scenarios where vascular segments experience significant hemodynamic fluctuations as it reinforces vascular wall integrity and preserves lumen patency. This can be valuable in treating veins prior to fistula creation and grafting or managing arterial aneurysm expansion. Full article
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16 pages, 6662 KiB  
Article
Ligand Composition and Coating Density Co-Modulate the Chondrocyte Function on Poly(glycerol-dodecanedioate)
by Yue Qin and Rhima M. Coleman
J. Funct. Biomater. 2023, 14(9), 468; https://doi.org/10.3390/jfb14090468 - 11 Sep 2023
Cited by 1 | Viewed by 1406
Abstract
Inducing chondrocyte redifferentiation and promoting cartilaginous matrix accumulation are key challenges in the application of biomaterials in articular cartilage repair. Poly(glycerol-dodecanedioate) (PGD) is a viable candidate for scaffold design in cartilage tissue engineering (CTE). However, the surface properties of PGD are not ideal [...] Read more.
Inducing chondrocyte redifferentiation and promoting cartilaginous matrix accumulation are key challenges in the application of biomaterials in articular cartilage repair. Poly(glycerol-dodecanedioate) (PGD) is a viable candidate for scaffold design in cartilage tissue engineering (CTE). However, the surface properties of PGD are not ideal for cell attachment and growth due to its relative hydrophobicity compared with natural extracellular matrix (ECM). In this study, PGD was coated with various masses of collagen type I or hyaluronic acid, individually or in combination, to generate a cell–material interface with biological cues. The effects of ligand composition and density on the PGD surface properties and shape, metabolic activity, cell phenotype, and ECM production of human articular chondrocytes (hACs) were evaluated. Introducing ECM ligands on PGD significantly improved its hydrophilicity and promoted the chondrocyte’s anabolic activity. The morphology and anabolic activity of hACs on PGD were co-modulated by ligand composition and density, suggesting a combinatorial effect of both coating parameters on chondrocyte function during monolayer culture. Hyaluronic acid and its combination with collagen maintained a round cell shape and redifferentiated phenotype. This study demonstrated the complex mechanism of ligand-guided interactions between cell and biomaterial substrate and the potential of PGD as a scaffold material in the field of CTE. Full article
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19 pages, 6917 KiB  
Article
In Vivo Evaluation of Collagen and Chitosan Scaffold, Associated or Not with Stem Cells, in Bone Repair
by Marcelo Rodrigues Da Cunha, Fernanda Latorre Melgaço Maia, Amilton Iatecola, Lívia Contini Massimino, Ana Maria de Guzzi Plepis, Virginia da Conceição Amaro Martins, Daniel Navarro Da Rocha, Eric Domingos Mariano, Mariáh Cationi Hirata, José Ricardo Muniz Ferreira, Marcelo Lucchesi Teixeira, Daniela Vieira Buchaim, Rogerio Leone Buchaim, Bruna Eduarda Gandra De Oliveira and André Antonio Pelegrine
J. Funct. Biomater. 2023, 14(7), 357; https://doi.org/10.3390/jfb14070357 - 8 Jul 2023
Cited by 5 | Viewed by 2189
Abstract
Natural polymers are increasingly being used in tissue engineering due to their ability to mimic the extracellular matrix and to act as a scaffold for cell growth, as well as their possible combination with other osteogenic factors, such as mesenchymal stem cells (MSCs) [...] Read more.
Natural polymers are increasingly being used in tissue engineering due to their ability to mimic the extracellular matrix and to act as a scaffold for cell growth, as well as their possible combination with other osteogenic factors, such as mesenchymal stem cells (MSCs) derived from dental pulp, in an attempt to enhance bone regeneration during the healing of a bone defect. Therefore, the aim of this study was to analyze the repair of mandibular defects filled with a new collagen/chitosan scaffold, seeded or not with MSCs derived from dental pulp. Twenty-eight rats were submitted to surgery for creation of a defect in the right mandibular ramus and divided into the following groups: G1 (control group; mandibular defect with clot); G2 (defect filled with dental pulp mesenchymal stem cells—DPSCs); G3 (defect filled with collagen/chitosan scaffold); and G4 (collagen/chitosan scaffold seeded with DPSCs). The analysis of the scaffold microstructure showed a homogenous material with an adequate percentage of porosity. Macroscopic and radiological examination of the defect area after 6 weeks post-surgery revealed the absence of complete repair, as well as absence of signs of infection, which could indicate rejection of the implants. Histomorphometric analysis of the mandibular defect area showed that bone formation occurred in a centripetal fashion, starting from the borders and progressing towards the center of the defect in all groups. Lower bone formation was observed in G1 when compared to the other groups and G2 exhibited greater osteoregenerative capacity, followed by G4 and G3. In conclusion, the scaffold used showed osteoconductivity, no foreign body reaction, malleability and ease of manipulation, but did not obtain promising results for association with DPSCs. Full article
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13 pages, 3162 KiB  
Article
Bacterial Cellulose/Cellulose Imidazolium Bio-Hybrid Membranes for In Vitro and Antimicrobial Applications
by Ahmed Salama, Ahmed K. Saleh, Iriczalli Cruz-Maya and Vincenzo Guarino
J. Funct. Biomater. 2023, 14(2), 60; https://doi.org/10.3390/jfb14020060 - 20 Jan 2023
Cited by 14 | Viewed by 2409
Abstract
In biomedical applications, bacterial cellulose (BC) is widely used because of its cytocompatibility, high mechanical properties, and ultrafine nanofibrillar structure. However, biomedical use of neat BC is often limited due to its lack of antimicrobial properties. In the current article, we proposed a [...] Read more.
In biomedical applications, bacterial cellulose (BC) is widely used because of its cytocompatibility, high mechanical properties, and ultrafine nanofibrillar structure. However, biomedical use of neat BC is often limited due to its lack of antimicrobial properties. In the current article, we proposed a novel technique for preparing cationic BC hydrogel through in situ incorporation of cationic water-soluble cellulose derivative, cellulose bearing imidazolium tosylate function group (Cell-IMD), in the media used for BC preparation. Different concentrations of cationic cellulose derivative (2, 4, and 6%) were embedded into a highly inter-twined BC nanofibrillar network through the in situ biosynthesis until forming cationic cellulose gels. Cationic functionalization was deeply examined by the Fourier transform infrared (FT–IR), NMR spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD) methods. In vitro studies with L929 cells confirmed a good cytocompatibility of BC/cationic cellulose derivatives, and a significant increase in cell proliferation after 7 days, in the case of BC/Cell-IMD3 groups. Finally, antimicrobial assessment against Staphylococcus aureus, Streptococcus mutans, and Candida albicans was assessed, recording a good sensitivity in the case of the higher concentration of the cationic cellulose derivative. All the results suggest a promising use of cationic hybrid materials for biomedical and bio-sustainable applications (i.e., food packaging). Full article
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Review

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20 pages, 1299 KiB  
Review
Recent Advances in Stem Cell Differentiation Control Using Drug Delivery Systems Based on Porous Functional Materials
by Yun-Sik Eom, Joon-Ha Park and Tae-Hyung Kim
J. Funct. Biomater. 2023, 14(9), 483; https://doi.org/10.3390/jfb14090483 - 20 Sep 2023
Cited by 2 | Viewed by 3389
Abstract
The unique characteristics of stem cells, which include self-renewal and differentiation into specific cell types, have paved the way for the development of various biomedical applications such as stem cell therapy, disease modelling, and drug screening. The establishment of effective stem cell differentiation [...] Read more.
The unique characteristics of stem cells, which include self-renewal and differentiation into specific cell types, have paved the way for the development of various biomedical applications such as stem cell therapy, disease modelling, and drug screening. The establishment of effective stem cell differentiation techniques is essential for the effective application of stem cells for various purposes. Ongoing research has sought to induce stem cell differentiation using diverse differentiation factors, including chemicals, proteins, and integrin expression. These differentiation factors play a pivotal role in a variety of applications. However, it is equally essential to acknowledge the potential hazards of uncontrolled differentiation. For example, uncontrolled differentiation can give rise to undesirable consequences, including cancerous mutations and stem cell death. Therefore, the development of innovative methods to control stem cell differentiation is crucial. In this review, we discuss recent research cases that have effectively utilised porous functional material-based drug delivery systems to regulate stem cell differentiation. Due to their unique substrate properties, drug delivery systems based on porous functional materials effectively induce stem cell differentiation through the steady release of differentiation factors. These ground-breaking techniques hold considerable promise for guiding and controlling the fate of stem cells for a wide range of biomedical applications, including stem cell therapy, disease modelling, and drug screening. Full article
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27 pages, 3021 KiB  
Review
Current Trend and New Opportunities for Multifunctional Bio-Scaffold Fabrication via High-Pressure Foaming
by María Alejandra Fanovich, Ernesto Di Maio and Aurelio Salerno
J. Funct. Biomater. 2023, 14(9), 480; https://doi.org/10.3390/jfb14090480 - 19 Sep 2023
Cited by 3 | Viewed by 1787
Abstract
Biocompatible and biodegradable foams prepared using the high-pressure foaming technique have been widely investigated in recent decades as porous scaffolds for in vitro and in vivo tissue growth. In fact, the foaming process can operate at low temperatures to load bioactive molecules and [...] Read more.
Biocompatible and biodegradable foams prepared using the high-pressure foaming technique have been widely investigated in recent decades as porous scaffolds for in vitro and in vivo tissue growth. In fact, the foaming process can operate at low temperatures to load bioactive molecules and cells within the pores of the scaffold, while the density and pore architecture, and, hence, properties of the scaffold, can be finely modulated by the proper selection of materials and processing conditions. Most importantly, the high-pressure foaming of polymers is an ideal choice to limit and/or avoid the use of cytotoxic and tissue-toxic compounds during scaffold preparation. The aim of this review is to provide the reader with the state of the art and current trend in the high-pressure foaming of biomedical polymers and composites towards the design and fabrication of multifunctional scaffolds for tissue engineering. This manuscript describes the application of the gas foaming process for bio-scaffold design and fabrication and highlights some of the most interesting results on: (1) the engineering of porous scaffolds featuring biomimetic porosity to guide cell behavior and to mimic the hierarchical architecture of complex tissues, such as bone; (2) the bioactivation of the scaffolds through the incorporation of inorganic fillers and drugs. Full article
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17 pages, 5009 KiB  
Review
Review on Bioinspired Design of ECM-Mimicking Scaffolds by Computer-Aided Assembly of Cell-Free and Cell Laden Micro-Modules
by Aurelio Salerno and Paolo Antonio Netti
J. Funct. Biomater. 2023, 14(2), 101; https://doi.org/10.3390/jfb14020101 - 13 Feb 2023
Cited by 8 | Viewed by 2820
Abstract
Tissue engineering needs bioactive drug delivery scaffolds capable of guiding cell biosynthesis and tissue morphogenesis in three dimensions. Several strategies have been developed to design and fabricate ECM-mimicking scaffolds suitable for directing in vitro cell/scaffold interaction, and controlling tissue morphogenesis in vivo. Among [...] Read more.
Tissue engineering needs bioactive drug delivery scaffolds capable of guiding cell biosynthesis and tissue morphogenesis in three dimensions. Several strategies have been developed to design and fabricate ECM-mimicking scaffolds suitable for directing in vitro cell/scaffold interaction, and controlling tissue morphogenesis in vivo. Among these strategies, emerging computer aided design and manufacturing processes, such as modular tissue unit patterning, promise to provide unprecedented control over the generation of biologically and biomechanically competent tissue analogues. This review discusses recent studies and highlights the role of scaffold microstructural properties and their drug release capability in cell fate control and tissue morphogenesis. Furthermore, the work highlights recent advances in the bottom-up fabrication of porous scaffolds and hybrid constructs through the computer-aided assembly of cell-free and/or cell-laden micro-modules. The advantages, current limitations, and future challenges of these strategies are described and discussed. Full article
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21 pages, 1727 KiB  
Review
Matrices Activated with Messenger RNA
by Raquel Martinez-Campelo and Marcos Garcia-Fuentes
J. Funct. Biomater. 2023, 14(1), 48; https://doi.org/10.3390/jfb14010048 - 15 Jan 2023
Cited by 1 | Viewed by 2416
Abstract
Over two decades of preclinical and clinical experience have confirmed that gene therapy-activated matrices are potent tools for sustained gene modulation at the implantation area. Matrices activated with messenger RNA (mRNA) are the latest development in the area, and they promise an ideal [...] Read more.
Over two decades of preclinical and clinical experience have confirmed that gene therapy-activated matrices are potent tools for sustained gene modulation at the implantation area. Matrices activated with messenger RNA (mRNA) are the latest development in the area, and they promise an ideal combination of efficiency and safety. Indeed, implanted mRNA-activated matrices allow a sustained delivery of mRNA and the continuous production of therapeutic proteins in situ. In addition, they are particularly interesting to generate proteins acting on intracellular targets, as the translated protein can directly exert its therapeutic function. Still, mRNA-activated matrices are incipient technologies with a limited number of published records, and much is still to be understood before their successful implementation. Indeed, the design parameters of mRNA-activated matrices are crucial for their performance, as they affect mRNA stability, device immunogenicity, translation efficiency, and the duration of the therapy. Critical design factors include matrix composition and its mesh size, mRNA chemical modification and sequence, and the characteristics of the nanocarriers used for mRNA delivery. This review aims to provide some background relevant to these technologies and to summarize both the design space for mRNA-activated matrices and the current knowledge regarding their pharmaceutical performance. Furthermore, we will discuss potential applications of mRNA-activated matrices, mainly focusing on tissue engineering and immunomodulation. Full article
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