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Advanced Bioscaffolds as Drivers of Modern Medicine

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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 (31 December 2021) | Viewed by 34783

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Prof. Dr. Barbara Lukomska

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Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego Str., 02-106 Warsaw, Poland
Interests: MSC, GRP and EV transplantation; stroke; ALS; neuroinflammation; biomaterials

Prof. Dr. Piotr Walczak

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School of Medicine, University of Maryland, Baltimore, MD, USA
Interests: image-guided drug delivery to the brain; biomaterials; MRI; stroke; brain tumors

Dr. Joaquim Miguel Oliveira

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1. 3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimarães, Portugal
2. ICVS/3B’s–PT Government Associate Laboratory, Braga, 4805-017 Guimarães, Portugal
Interests: nanobiomaterials; nanomedicine; theranostics; tissue engineering; bio 3D printing; 3D in vitro tissue models of disease
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Dear Colleagues,

The traditional dichotomy of surgery and small molecule-based therapeutics gradually blurs with the arrival of increasingly sophisticated healthcare solutions, which are becoming a determinant of modern medicine. A variety of active pharmaceutical and biological ingredients span across proteins, lipids, nucleic acids, nanoparticles and even living cellular products. Notably, traditional systemic routes of their delivery reach limits. Bioscaffolds are becoming an increasingly attractive option for minimally invasive and spatially targeted delivery of increasingly complex therapeutic solutions. The local nature of bioscaffold-based routes may also minimize whole-body side effects plaguing traditional, systemic routes of drug delivery. Therefore, there is a momentum for advancing bioscaffold research.

For this Issue, we are inviting scientists focused on bioscaffold research to present the progress in the regions of their interests. One compelling frontier in this field is bioscaffold labeling for non-invasive imaging. The efforts toward mimicking the extracellular matrix by the introduction of bio-inspired scaffolds are also very tempting. The use of bioscaffolds as prolonged drug delivery systems will also be welcome. Ultimately, we envision to feature in our Issue smart bioscaffolds with a remote and precisely controlled drug release and tuning. In summary, we expect to collect a series of articles on cutting-edge bioscaffold research.

Prof. Dr. Barbara Lukomska
Prof. Dr. Piotr Walczak
Prof. Dr. Joaquim Miguel Oliveira
Guest Editors

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Keywords

bioscaffolds
imaging
drug carriers, targeted therapy
hydrogel
precision medicine

Published Papers (11 papers)

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Research

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18 pages, 7256 KiB

Open AccessArticle

Manganese-Labeled Alginate Hydrogels for Image-Guided Cell Transplantation

by Antonina M. Araszkiewicz, Eduarda P. Oliveira, Terje Svendsen, Katarzyna Drela, Piotr Rogujski, Izabela Malysz-Cymborska, Michal Fiedorowicz, Rui L. Reis, Joaquim Miguel Oliveira, Piotr Walczak, Miroslaw Janowski, Barbara Lukomska and Luiza Stanaszek

Int. J. Mol. Sci. 2022, 23(5), 2465; https://doi.org/10.3390/ijms23052465 - 23 Feb 2022

Cited by 4 | Viewed by 2162

Abstract

Cell transplantation has been studied extensively as a therapeutic strategy for neurological disorders. However, to date, its effectiveness remains unsatisfactory due to low precision and efficacy of cell delivery; poor survival of transplanted cells; and inadequate monitoring of their fate in vivo. Fortunately, different bio-scaffolds have been proposed as cell carriers to improve the accuracy of cell delivery, survival, differentiation, and controlled release of embedded stem cells. The goal of our study was to establish hydrogel scaffolds suitable for stem cell delivery that also allow non-invasive magnetic resonance imaging (MRI). We focused on alginate-based hydrogels due to their natural origin, biocompatibility, resemblance to the extracellular matrix, and easy manipulation of gelation processes. We optimized the properties of alginate-based hydrogels, turning them into suitable carriers for transplanted cells. Human adipose-derived stem cells embedded in these hydrogels survived for at least 14 days in vitro. Alginate-based hydrogels were also modified successfully to allow their injectability via a needle. Finally, supplementing alginate hydrogels with Mn ions or Mn nanoparticles allowed for their visualization in vivo using manganese-enhanced MRI. We demonstrated that modified alginate-based hydrogels can support therapeutic cells as MRI-detectable matrices. Full article

(This article belongs to the Special Issue Advanced Bioscaffolds as Drivers of Modern Medicine)

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15 pages, 3128 KiB

Open AccessArticle

Creating a Natural Vascular Scaffold by Photochemical Treatment of the Extracellular Matrix for Vascular Applications

by Katalin Kauser, Kevin S. Warner, Blake Anderson, Edgar Dalles Keyes, RB Hayes, Eric Kawamoto, DH Perkins, Robert Scott, Jim Isaacson, Barb Haberer, Ann Spaans, Ronald Utecht, Hank Hauser, Andrew George Roberts and Myles Greenberg

Int. J. Mol. Sci. 2022, 23(2), 683; https://doi.org/10.3390/ijms23020683 - 08 Jan 2022

Cited by 4 | Viewed by 2453

Abstract

The development of bioscaffolds for cardiovascular medical applications, such as peripheral artery disease (PAD), remains to be a challenge for tissue engineering. PAD is an increasingly common and serious cardiovascular illness characterized by progressive atherosclerotic stenosis, resulting in decreased blood perfusion to the lower extremities. Percutaneous transluminal angioplasty and stent placement are routinely performed on these patients with suboptimal outcomes. Natural Vascular Scaffolding (NVS) is a novel treatment in the development for PAD, which offers an alternative to stenting by building on the natural structural constituents in the extracellular matrix (ECM) of the blood vessel wall. During NVS treatment, blood vessels are exposed to a photoactivatable small molecule (10-8-10 Dimer) delivered locally to the vessel wall via an angioplasty balloon. When activated with 450 nm wavelength light, this therapy induces the formation of covalent protein–protein crosslinks of the ECM proteins by a photochemical mechanism, creating a natural scaffold. This therapy has the potential to reduce the need for stent placement by maintaining a larger diameter post-angioplasty and minimizing elastic recoil. Experiments were conducted to elucidate the mechanism of action of NVS, including the molecular mechanism of light activation and the impact of NVS on the ECM. Full article

(This article belongs to the Special Issue Advanced Bioscaffolds as Drivers of Modern Medicine)

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20 pages, 3970 KiB

Open AccessArticle

Multiscale-Engineered Muscle Constructs: PEG Hydrogel Micro-Patterning on an Electrospun PCL Mat Functionalized with Gold Nanoparticles

by Megane Beldjilali-Labro, Rachid Jellali, Alexander David Brown, Alejandro Garcia Garcia, Augustin Lerebours, Erwann Guenin, Fahmi Bedoui, Murielle Dufresne, Claire Stewart, Jean-François Grosset and Cécile Legallais

Int. J. Mol. Sci. 2022, 23(1), 260; https://doi.org/10.3390/ijms23010260 - 27 Dec 2021

Cited by 7 | Viewed by 3401

Abstract

The development of new, viable, and functional engineered tissue is a complex and challenging task. Skeletal muscle constructs have specific requirements as cells are sensitive to the stiffness, geometry of the materials, and biological micro-environment. The aim of this study was thus to design and characterize a multi-scale scaffold and to evaluate it regarding the differentiation process of C2C12 skeletal myoblasts. The significance of the work lies in the microfabrication of lines of polyethylene glycol, on poly(ε-caprolactone) nanofiber sheets obtained using the electrospinning process, coated or not with gold nanoparticles to act as a potential substrate for electrical stimulation. The differentiation of C2C12 cells was studied over a period of seven days and quantified through both expression of specific genes, and analysis of the myotubes’ alignment and length using confocal microscopy. We demonstrated that our multiscale bio-construct presented tunable mechanical properties and supported the different stages skeletal muscle, as well as improving the parallel orientation of the myotubes with a variation of less than 15°. These scaffolds showed the ability of sustained myogenic differentiation by enhancing the organization of reconstructed skeletal muscle. Moreover, they may be suitable for applications in mechanical and electrical stimulation to mimic the muscle’s physiological functions. Full article

(This article belongs to the Special Issue Advanced Bioscaffolds as Drivers of Modern Medicine)

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15 pages, 3161 KiB

Open AccessArticle

Human Periodontal Ligament Stem Cell and Umbilical Vein Endothelial Cell Co-Culture to Prevascularize Scaffolds for Angiogenic and Osteogenic Tissue Engineering

by Zeqing Zhao, Yaxi Sun, Qingchen Qiao, Li Zhang, Xianju Xie, Michael D. Weir, Abraham Schneider, Hockin H. K. Xu, Ning Zhang, Ke Zhang and Yuxing Bai

Int. J. Mol. Sci. 2021, 22(22), 12363; https://doi.org/10.3390/ijms222212363 - 16 Nov 2021

Cited by 12 | Viewed by 2209

Abstract

(1) Background: Vascularization remains a critical challenge in bone tissue engineering. The objective of this study was to prevascularize calcium phosphate cement (CPC) scaffold by co-culturing human periodontal ligament stem cells (hPDLSCs) and human umbilical vein endothelial cells (hUVECs) for the first time; (2) Methods: hPDLSCs and/or hUVECs were seeded on CPC scaffolds. Three groups were tested: (i) hUVEC group (hUVECs on CPC); (ii) hPDLSC group (hPDLSCs on CPC); (iii) co-culture group (hPDLSCs + hUVECs on CPC). Osteogenic differentiation, bone mineral synthesis, and microcapillary-like structures were evaluated; (3) Results: Angiogenic gene expressions of co-culture group were 6–9 fold those of monoculture. vWF expression of co-culture group was 3 times lower than hUVEC-monoculture group. Osteogenic expressions of co-culture group were 2–3 folds those of the hPDLSC-monoculture group. ALP activity and bone mineral synthesis of co-culture were much higher than hPDLSC-monoculture group. Co-culture group formed capillary-like structures at 14–21 days. Vessel length and junction numbers increased with time; (4) Conclusions: The hUVECs + hPDLSCs co-culture on CPC scaffold achieved excellent osteogenic and angiogenic capability in vitro for the first time, generating prevascularized networks. The hPDLSCs + hUVECs co-culture had much better osteogenesis and angiogenesis than monoculture. CPC scaffolds prevacularized via hPDLSCs + hUVECs are promising for dental, craniofacial, and orthopedic applications. Full article

(This article belongs to the Special Issue Advanced Bioscaffolds as Drivers of Modern Medicine)

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22 pages, 28010 KiB

Open AccessArticle

Activated Carbon Fiber Cloth/Biomimetic Apatite: A Dual Drug Delivery System

by Florian Olivier, Sylvie Bonnamy, Nathalie Rochet and Christophe Drouet

Int. J. Mol. Sci. 2021, 22(22), 12247; https://doi.org/10.3390/ijms222212247 - 12 Nov 2021

Cited by 10 | Viewed by 1988

Abstract

A biomaterial that is both bioactive and capable of controlled drug release is highly attractive for bone regeneration. In previous works, we demonstrated the possibility of combining activated carbon fiber cloth (ACC) and biomimetic apatite (such as calcium-deficient hydroxyapatite (CDA)) to develop an efficient material for bone regeneration. The aim to use the adsorption properties of an activated carbon/biomimetic apatite composite to synthetize a biomaterial to be used as a controlled drug release system after implantation. The adsorption and desorption of tetracycline and aspirin were first investigated in the ACC and CDA components and then on ACC/CDA composite. The results showed that drug adsorption and release are dependent on the adsorbent material and the drug polarity/hydrophilicity, leading to two distinct modes of drug adsorption and release. Consequently, a double adsorption approach was successfully performed, leading to a multifunctional and innovative ACC-aspirin/CDA-tetracycline implantable biomaterial. In a second step, in vitro tests emphasized a better affinity of the drug (tetracycline or aspirin)-loaded ACC/CDA materials towards human primary osteoblast viability and proliferation. Then, in vivo experiments on a large cortical bone defect in rats was carried out to test biocompatibility and bone regeneration ability. Data clearly highlighted a significant acceleration of bone reconstruction in the presence of the ACC/CDA patch. The ability of the aspirin-loaded ACC/CDA material to release the drug in situ for improving bone healing was also underlined, as a proof of concept. This work highlights the possibility of bone patches with controlled (multi)drug release features being used for bone tissue repair. Full article

(This article belongs to the Special Issue Advanced Bioscaffolds as Drivers of Modern Medicine)

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14 pages, 7524 KiB

Open AccessCommunication

Synthesis and Investigations of Building Blocks with Dibenzo[b,f] Oxepine for Use in Photopharmacology

by Piotr Tobiasz, Filip Borys, Marta Borecka and Hanna Krawczyk

Int. J. Mol. Sci. 2021, 22(20), 11033; https://doi.org/10.3390/ijms222011033 - 13 Oct 2021

Cited by 4 | Viewed by 1763

Abstract

The synthesis of photoswitchable azo-dibenzo[b,f]oxepine derivatives and microtubule inhibitors were described. Subsequently, we examined the reaction of methoxy derivative 3-nitrodibenzo[b,f]oxepine with different aldehydes and in the presence of BF₃·OEt₂ as a catalyst. Our study provided a very concise method for the construction of the azo-dibenzo[b,f]oxepine skeleton. The analysis of products was run using experimental and theoretical methods. Next, we evaluated the E/Z isomerization of azo-dibenzo[b,f]oxepine derivatives, which could be photochemically controlled using visible-wavelength light. Full article

(This article belongs to the Special Issue Advanced Bioscaffolds as Drivers of Modern Medicine)

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17 pages, 3949 KiB

Open AccessArticle

Dye-Mediated Photo-Oxidation Biomaterial Fixation: Analysis of Bioinductivity and Mechanical Properties of Bovine Pericardium for Use in Cardiac Surgery

by Simranjit S. Pattar, Vishnu Vasanthan, Guoqi Teng, Karl T. Wagner, Kristina Jeon, Sean Kang, Ali Fatehi Hassanabad and Paul W. M. Fedak

Int. J. Mol. Sci. 2021, 22(19), 10768; https://doi.org/10.3390/ijms221910768 - 05 Oct 2021

Viewed by 1612

Abstract

Extracellular matrix bioscaffolds can influence the cardiac microenvironment and modulate endogenous cellular mechanisms. These materials can optimize cardiac surgery for repair and reconstruction. We investigated the biocompatibility and bioinductivity of bovine pericardium fixed via dye-mediated photo-oxidation on human cardiac fibroblast activity. We compared a dye-mediated photo-oxidation fixed bioscaffold to glutaraldehyde-fixed and non-fixed bioscaffolds reported in contemporary literature in cardiac surgery. Human cardiac fibroblasts from consenting patients were seeded on to bioscaffold materials to assess the biocompatibility and bioinductivity. Human cardiac fibroblast gene expression, secretome, morphology and viability were studied. Dye-mediated photo-oxidation fixed acellular bovine pericardium preserves human cardiac fibroblast phenotype and viability; and potentiates a pro-vasculogenic paracrine response. Material tensile properties were compared with biomechanical testing. Dye-mediated photo-oxidation fixed acellular bovine pericardium had higher compliance compared to glutaraldehyde-fixed bioscaffold in response to tensile force. The biocompatibility, bioinductivity, and biomechanical properties of dye-mediated photo-oxidation fixed bovine pericardium demonstrate its feasibility as a bioscaffold for use in cardiac surgery. As a fixed yet bioinductive solution, this bioscaffold demonstrates enhanced compliance and retains bioinductive properties that may leverage endogenous reparative pathways. Dye-mediated photo-oxidation fixed bioscaffold warrants further investigation as a viable tool for cardiac repair and reconstruction. Full article

(This article belongs to the Special Issue Advanced Bioscaffolds as Drivers of Modern Medicine)

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19 pages, 5501 KiB

Open AccessArticle

Synergistic Effect of PVDF-Coated PCL-TCP Scaffolds and Pulsed Electromagnetic Field on Osteogenesis

by Yibing Dong, Luvita Suryani, Xinran Zhou, Padmalosini Muthukumaran, Moumita Rakshit, Fengrui Yang, Feng Wen, Ammar Mansoor Hassanbhai, Kaushik Parida, Daniel T. Simon, Donata Iandolo, Pooi See Lee, Kee Woei Ng and Swee Hin Teoh

Int. J. Mol. Sci. 2021, 22(12), 6438; https://doi.org/10.3390/ijms22126438 - 16 Jun 2021

Cited by 17 | Viewed by 3956

Abstract

Bone exhibits piezoelectric properties. Thus, electrical stimulations such as pulsed electromagnetic fields (PEMFs) and stimuli-responsive piezoelectric properties of scaffolds have been investigated separately to evaluate their efficacy in supporting osteogenesis. However, current understanding of cells responding under the combined influence of PEMF and piezoelectric properties in scaffolds is still lacking. Therefore, in this study, we fabricated piezoelectric scaffolds by functionalization of polycaprolactone-tricalcium phosphate (PCL-TCP) films with a polyvinylidene fluoride (PVDF) coating that is self-polarized by a modified breath-figure technique. The osteoinductive properties of these PVDF-coated PCL-TCP films on MC3T3-E1 cells were studied under the stimulation of PEMF. Piezoelectric and ferroelectric characterization demonstrated that scaffolds with piezoelectric coefficient d₃₃ = −1.2 pC/N were obtained at a powder dissolution temperature of 100 °C and coating relative humidity (RH) of 56%. DNA quantification showed that cell proliferation was significantly enhanced by PEMF as low as 0.6 mT and 50 Hz. Hydroxyapatite staining showed that cell mineralization was significantly enhanced by incorporation of PVDF coating. Gene expression study showed that the combination of PEMF and PVDF coating promoted late osteogenic gene expression marker most significantly. Collectively, our results suggest that the synergistic effects of PEMF and piezoelectric scaffolds on osteogenesis provide a promising alternative strategy for electrically augmented osteoinduction. The piezoelectric response of PVDF by PEMF, which could provide mechanical strain, is particularly interesting as it could deliver local mechanical stimulation to osteogenic cells using PEMF. Full article

(This article belongs to the Special Issue Advanced Bioscaffolds as Drivers of Modern Medicine)

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Review

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19 pages, 997 KiB

Open AccessReview

An Update on Graphene-Based Nanomaterials for Neural Growth and Central Nervous System Regeneration

by Maria Grazia Tupone, Gloria Panella, Michele d’Angelo, Vanessa Castelli, Giulia Caioni, Mariano Catanesi, Elisabetta Benedetti and Annamaria Cimini

Int. J. Mol. Sci. 2021, 22(23), 13047; https://doi.org/10.3390/ijms222313047 - 02 Dec 2021

Cited by 15 | Viewed by 2804

Abstract

Thanks to their reduced size, great surface area, and capacity to interact with cells and tissues, nanomaterials present some attractive biological and chemical characteristics with potential uses in the field of biomedical applications. In this context, graphene and its chemical derivatives have been extensively used in many biomedical research areas from drug delivery to bioelectronics and tissue engineering. Graphene-based nanomaterials show excellent optical, mechanical, and biological properties. They can be used as a substrate in the field of tissue engineering due to their conductivity, allowing to study, and educate neural connections, and guide neural growth and differentiation; thus, graphene-based nanomaterials represent an emerging aspect in regenerative medicine. Moreover, there is now an urgent need to develop multifunctional and functionalized nanomaterials able to arrive at neuronal cells through the blood-brain barrier, to manage a specific drug delivery system. In this review, we will focus on the recent applications of graphene-based nanomaterials in vitro and in vivo, also combining graphene with other smart materials to achieve the best benefits in the fields of nervous tissue engineering and neural regenerative medicine. We will then highlight the potential use of these graphene-based materials to construct graphene 3D scaffolds able to stimulate neural growth and regeneration in vivo for clinical applications. Full article

(This article belongs to the Special Issue Advanced Bioscaffolds as Drivers of Modern Medicine)

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23 pages, 2156 KiB

Open AccessReview

The ECM: To Scaffold, or Not to Scaffold, That Is the Question

by Jonard Corpuz Valdoz, Benjamin C. Johnson, Dallin J. Jacobs, Nicholas A. Franks, Ethan L. Dodson, Cecilia Sanders, Collin G. Cribbs and Pam M. Van Ry

Int. J. Mol. Sci. 2021, 22(23), 12690; https://doi.org/10.3390/ijms222312690 - 24 Nov 2021

Cited by 53 | Viewed by 4944

Abstract

The extracellular matrix (ECM) has pleiotropic effects, ranging from cell adhesion to cell survival. In tissue engineering, the use of ECM and ECM-like scaffolds has separated the field into two distinct areas—scaffold-based and scaffold-free. Scaffold-free techniques are used in creating reproducible cell aggregates which have massive potential for high-throughput, reproducible drug screening and disease modeling. Though, the lack of ECM prevents certain cells from surviving and proliferating. Thus, tissue engineers use scaffolds to mimic the native ECM and produce organotypic models which show more reliability in disease modeling. However, scaffold-based techniques come at a trade-off of reproducibility and throughput. To bridge the tissue engineering dichotomy, we posit that finding novel ways to incorporate the ECM in scaffold-free cultures can synergize these two disparate techniques. Full article

(This article belongs to the Special Issue Advanced Bioscaffolds as Drivers of Modern Medicine)

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25 pages, 41246 KiB

Open AccessReview

The Emerging Role of Decellularized Plant-Based Scaffolds as a New Biomaterial

by Ashlee F. Harris, Jerome Lacombe and Frederic Zenhausern

Int. J. Mol. Sci. 2021, 22(22), 12347; https://doi.org/10.3390/ijms222212347 - 16 Nov 2021

Cited by 21 | Viewed by 5209

Abstract

The decellularization of plant-based biomaterials to generate tissue-engineered substitutes or in vitro cellular models has significantly increased in recent years. These vegetal tissues can be sourced from plant leaves and stems or fruits and vegetables, making them a low-cost, accessible, and sustainable resource from which to generate three-dimensional scaffolds. Each construct is distinct, representing a wide range of architectural and mechanical properties as well as innate vasculature networks. Based on the rapid rise in interest, this review aims to detail the current state of the art and presents the future challenges and perspectives of these unique biomaterials. First, we consider the different existing decellularization techniques, including chemical, detergent-free, enzymatic, and supercritical fluid approaches that are used to generate such scaffolds and examine how these protocols can be selected based on plant cellularity. We next examine strategies for cell seeding onto the plant-derived constructs and the importance of the different functionalization methods used to assist in cell adhesion and promote cell viability. Finally, we discuss how their structural features, such as inherent vasculature, porosity, morphology, and mechanical properties (i.e., stiffness, elasticity, etc.) position plant-based scaffolds as a unique biomaterial and drive their use for specific downstream applications. The main challenges in the field are presented throughout the discussion, and future directions are proposed to help improve the development and use of vegetal constructs in biomedical research. Full article

(This article belongs to the Special Issue Advanced Bioscaffolds as Drivers of Modern Medicine)

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