Biomolecules

Editorial

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5 pages, 205 KiB

Open AccessEditorial

Novel Targets and Therapeutic Strategies for Promoting Organ Repair and Regeneration

by Shanmugam Muruganandan and Michael Wigerius

Biomolecules 2020, 10(5), 749; https://doi.org/10.3390/biom10050749 - 12 May 2020

Viewed by 1627

Abstract

Strategies to create functional organs and tissues is of great interest for use in regenerative medicine in order to repair or replace the lost tissues due to injury, disease, as well as aging. Several new treatment options, including stem cell treatments and tissue-engineered [...] Read more.

Strategies to create functional organs and tissues is of great interest for use in regenerative medicine in order to repair or replace the lost tissues due to injury, disease, as well as aging. Several new treatment options, including stem cell treatments and tissue-engineered substitutes for certain indications, have been approved by Food and Drug Administration (FDA) and are currently available. This special issue will cover new therapies and strategies that are currently being investigated under preclinical and clinical settings. Full article

(This article belongs to the Special Issue New Targets and Strategies in Regenerative Medicine)

Research

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25 pages, 4454 KiB

Open AccessArticle

A Comprehensive Comparison of Bovine and Porcine Decellularized Pericardia: New Insights for Surgical Applications

by Sabra Zouhair, Eleonora Dal Sasso, Sugat R. Tuladhar, Catia Fidalgo, Luca Vedovelli, Andrea Filippi, Giulia Borile, Andrea Bagno, Massimo Marchesan, Giorgio De Rossi, Dario Gregori, Willem F. Wolkers, Filippo Romanato, Sotirios Korossis, Gino Gerosa and Laura Iop

Biomolecules 2020, 10(3), 371; https://doi.org/10.3390/biom10030371 - 28 Feb 2020

Cited by 45 | Viewed by 6997

Abstract

Xenogeneic pericardium-based substitutes are employed for several surgical indications after chemical shielding, limiting their biocompatibility and therapeutic durability. Adverse responses to these replacements might be prevented by tissue decellularization, ideally removing cells and preserving the original extracellular matrix (ECM). The aim of this [...] Read more.

Xenogeneic pericardium-based substitutes are employed for several surgical indications after chemical shielding, limiting their biocompatibility and therapeutic durability. Adverse responses to these replacements might be prevented by tissue decellularization, ideally removing cells and preserving the original extracellular matrix (ECM). The aim of this study was to compare the mostly applied pericardia in clinics, i.e., bovine and porcine tissues, after their decellularization, and obtain new insights for their possible surgical use. Bovine and porcine pericardia were submitted to TRICOL decellularization, based on osmotic shock, detergents and nuclease treatment. TRICOL procedure resulted in being effective in cell removal and preservation of ECM architecture of both species’ scaffolds. Collagen and elastin were retained but glycosaminoglycans were reduced, significantly for bovine scaffolds. Tissue hydration was varied by decellularization, with a rise for bovine pericardia and a decrease for porcine ones. TRICOL significantly increased porcine pericardial thickness, while a non-significant reduction was observed for the bovine counterpart. The protein secondary structure and thermal denaturation profile of both species’ scaffolds were unaltered. Both pericardial tissues showed augmented biomechanical compliance after decellularization. The ECM bioactivity of bovine and porcine pericardia was unaffected by decellularization, sustaining viability and proliferation of human mesenchymal stem cells and endothelial cells. In conclusion, decellularized bovine and porcine pericardia demonstrate possessing the characteristics that are suitable for the creation of novel scaffolds for reconstruction or replacement: differences in water content, thickness and glycosaminoglycans might influence some of their biomechanical properties and, hence, their indication for surgical use. Full article

(This article belongs to the Special Issue New Targets and Strategies in Regenerative Medicine)

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23 pages, 3118 KiB

Open AccessArticle

hNGF Peptides Elicit the NGF-TrkA Signalling Pathway in Cholinergic Neurons and Retain Full Neurotrophic Activity in the DRG Assay

by Viviana Triaca, Elena Fico, Valentina Sposato, Silvia Caioli, Maria Teresa Ciotti, Cristina Zona, Delio Mercanti, Diego La Mendola, Cristina Satriano, Enrico Rizzarelli, Paola Tirassa and Pietro Calissano

Biomolecules 2020, 10(2), 216; https://doi.org/10.3390/biom10020216 - 01 Feb 2020

Cited by 9 | Viewed by 3821

Abstract

In the last decade, Nerve Growth Factor (NGF)-based clinical approaches have lacked specific and efficient Tyrosine Kinase A (TrkA) agonists for brain delivery. Nowadays, the characterization of novel small peptidomimetic is taking centre stage in preclinical studies, in order to overcome the main [...] Read more.

In the last decade, Nerve Growth Factor (NGF)-based clinical approaches have lacked specific and efficient Tyrosine Kinase A (TrkA) agonists for brain delivery. Nowadays, the characterization of novel small peptidomimetic is taking centre stage in preclinical studies, in order to overcome the main size-related limitation in brain delivery of NGF holoprotein for Central Nervous System (CNS) pathologies. Here we investigated the NGF mimetic properties of the human NGF 1–14 sequence (hNGF1–14) and its derivatives, by resorting to primary cholinergic and dorsal root ganglia (DRG) neurons. Briefly, we observed that: 1) hNGF1–14 peptides engage the NGF pathway through TrkA phosphorylation at tyrosine 490 (Y490), and activation of ShcC/PI3K and Plc-γ/MAPK signalling, promoting AKT-dependent survival and CREB-driven neuronal activity, as seen by levels of the immediate early gene c-Fos, of the cholinergic marker Choline Acetyltransferase (ChAT), and of Brain Derived Neurotrophic Factor (BDNF); 2) their NGF mimetic activity is lost upon selective TrkA inhibition by means of GW441756; 3) hNGF1–14 peptides are able to sustain DRG survival and differentiation in absence of NGF. Furthermore, the acetylated derivative Ac-hNGF1–14 demonstrated an optimal NGF mimetic activity in both neuronal paradigms and an electrophysiological profile similar to NGF in cholinergic neurons. Cumulatively, the findings here reported pinpoint the hNGF1–14 peptide, and in particular its acetylated derivative, as novel, specific and low molecular weight TrkA specific agonists in both CNS and PNS primary neurons. Full article

(This article belongs to the Special Issue New Targets and Strategies in Regenerative Medicine)

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19 pages, 7095 KiB

Open AccessArticle

Serine Protease Inhibitors—New Molecules for Modification of Polymeric Biomaterials

by Katarzyna Szałapata, Monika Osińska-Jaroszuk, Justyna Kapral-Piotrowska, Bożena Pawlikowska-Pawlęga, Rafał Łopucki, Robert Mroczka and Anna Jarosz-Wilkołazka

Biomolecules 2020, 10(1), 82; https://doi.org/10.3390/biom10010082 - 04 Jan 2020

Cited by 8 | Viewed by 3214

Abstract

Three serine protease inhibitors (AEBSF, soy inhibitor, α₁-antitrypsin) were covalently immobilized on the surface of three polymer prostheses with the optimized method. The immobilization efficiency ranged from 11 to 51%, depending on the chosen inhibitor and biomaterial. The highest activity for [...] Read more.

Three serine protease inhibitors (AEBSF, soy inhibitor, α₁-antitrypsin) were covalently immobilized on the surface of three polymer prostheses with the optimized method. The immobilization efficiency ranged from 11 to 51%, depending on the chosen inhibitor and biomaterial. The highest activity for all inhibitors was observed in the case of immobilization on the surface of the polyester Uni-Graft prosthesis, and the preparations obtained showed high stability in the environment with different pH and temperature values. Modification of the Uni-Graft prosthesis surface with the synthetic AEBSF inhibitor and human α₁-antitrypsin inhibited the adhesion and multiplication of Staphylococcus aureus subs. aureus ATCC^® 25923^TM and Candida albicans from the collection of the Department of Genetics and Microbiology, UMCS. Optical profilometry analysis indicated that, after the immobilization process on the surface of AEBSF-modified Uni-Graft prostheses, there were more structures with a high number of protrusions, while the introduction of modifications with a protein inhibitor led to the smoothing of their surface. Full article

(This article belongs to the Special Issue New Targets and Strategies in Regenerative Medicine)

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28 pages, 6945 KiB

Open AccessArticle

Mesenchymal Stem Cell Therapy for Spinal Cord Contusion: A Comparative Study on Small and Large Animal Models

by Yana Mukhamedshina, Iliya Shulman, Sergei Ogurcov, Alexander Kostennikov, Elena Zakirova, Elvira Akhmetzyanova, Alexander Rogozhin, Galina Masgutova, Victoria James, Ruslan Masgutov, Igor Lavrov and Albert Rizvanov

Biomolecules 2019, 9(12), 811; https://doi.org/10.3390/biom9120811 - 01 Dec 2019

Cited by 36 | Viewed by 5489

Abstract

Here, we provide a first comparative study of the therapeutic potential of allogeneic mesenchymal stem cells derived from bone marrow (BM-MSCs), adipose tissue (AD-MSCs), and dental pulp (DP-MSCs) embedded in fibrin matrix, in small (rat) and large (pig) spinal cord injury (SCI) models [...] Read more.

Here, we provide a first comparative study of the therapeutic potential of allogeneic mesenchymal stem cells derived from bone marrow (BM-MSCs), adipose tissue (AD-MSCs), and dental pulp (DP-MSCs) embedded in fibrin matrix, in small (rat) and large (pig) spinal cord injury (SCI) models during subacute period of spinal contusion. Results of behavioral, electrophysiological, and histological assessment as well as immunohistochemistry and real-time polymerase chain reaction analysis suggest that application of AD-MSCs combined with a fibrin matrix within the subacute period in rats (2 weeks after injury), provides significantly higher post-traumatic regeneration compared to a similar application of BM-MSCs or DP-MSCs. Within the rat model, use of AD-MSCs resulted in a marked change in: (1) restoration of locomotor activity and conduction along spinal axons; (2) reduction of post-traumatic cavitation and enhancing tissue retention; and (3) modulation of microglial and astroglial activation. The effect of an autologous application of AD-MSCs during the subacute period after spinal contusion was also confirmed in pigs (6 weeks after injury). Effects included: (1) partial restoration of the somatosensory spinal pathways; (2) reduction of post-traumatic cavitation and enhancing tissue retention; and (3) modulation of astroglial activation in dorsal root entry zone. However, pigs only partially replicated the findings observed in rats. Together, these results indicate application of AD-MSCs embedded in fibrin matrix at the site of SCI during the subacute period can facilitate regeneration of nervous tissue in rats and pigs. These results, for the first time, provide robust support for the use of AD-MSC to treat subacute SCI. Full article

(This article belongs to the Special Issue New Targets and Strategies in Regenerative Medicine)

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18 pages, 2940 KiB

Open AccessArticle

Predicting Angiogenesis by Endothelial Progenitor Cells Relying on In-Vitro Function Assays and VEGFR-2 Expression Levels

by Nadin Sabbah, Tal Tamari, Rina Elimelech, Ofri Doppelt, Utai Rudich and Hadar Zigdon-Giladi

Biomolecules 2019, 9(11), 717; https://doi.org/10.3390/biom9110717 - 08 Nov 2019

Cited by 8 | Viewed by 2861

Abstract

Clinical trials have demonstrated the safety and efficacy of autologous endothelial progenitor cell (EPC) therapy in various diseases. Since EPCs’ functions are influenced by genetic, systemic and environmental factors, the therapeutic potential of each individual EPCs is unknown and may affect treatment outcome. [...] Read more.

Clinical trials have demonstrated the safety and efficacy of autologous endothelial progenitor cell (EPC) therapy in various diseases. Since EPCs’ functions are influenced by genetic, systemic and environmental factors, the therapeutic potential of each individual EPCs is unknown and may affect treatment outcome. Therefore, our aim was to compare EPCs function among healthy donors in order to predict blood vessel formation (angiogenesis) before autologous EPC transplantation. Human EPCs were isolated from the blood of ten volunteers. EPCs proliferation rate, chemoattractant ability, and CXCR4 mRNA levels were different among donors (p < 0.0001, p < 0.01, p < 0.001, respectively). A positive correlation was found between SDF-1, CXCR4, and EPCs proliferation (R = 0.736, p < 0.05 and R = 0.8, p < 0.01, respectively). In-vivo, blood vessels were counted ten days after EPCs transplantation in a subcutaneous mouse model. Mean vessel density was different among donors (p = 0.0001); nevertheless, donors with the lowest vessel densities were higher compared to control (p < 0.05). Finally, using a linear regression model, a mathematical equation was generated to predict blood vessel density relying on: (i) EPCs chemoattractivity, and (ii) VEGFR-2 mRNA levels. Results reveal differences in EPCs functions among healthy individuals, emphasizing the need for a potency assay to pave the way for standardized research and clinical use of human EPCs. Full article

(This article belongs to the Special Issue New Targets and Strategies in Regenerative Medicine)

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16 pages, 5372 KiB

Open AccessArticle

Strategies for Developing Functional Secretory Epithelia from Porcine Salivary Gland Explant Outgrowth Culture Models

by Ganokon Urkasemsin, Phoebe Castillo, Sasitorn Rungarunlert, Nuttha Klincumhom and Joao N. Ferreira

Biomolecules 2019, 9(11), 657; https://doi.org/10.3390/biom9110657 - 25 Oct 2019

Cited by 8 | Viewed by 3255

Abstract

Research efforts have been made to develop human salivary gland (SG) secretory epithelia for transplantation in patients with SG hypofunction and dry mouth (xerostomia). However, the limited availability of human biopsies hinders the generation of sufficient cell numbers for epithelia formation and regeneration. [...] Read more.

Research efforts have been made to develop human salivary gland (SG) secretory epithelia for transplantation in patients with SG hypofunction and dry mouth (xerostomia). However, the limited availability of human biopsies hinders the generation of sufficient cell numbers for epithelia formation and regeneration. Porcine SG have several similarities to their human counterparts, hence could replace human cells in SG modelling studies in vitro. Our study aims to establish porcine SG explant outgrowth models to generate functional secretory epithelia for regeneration purposes to rescue hyposalivation. Cells were isolated and expanded from porcine submandibular and parotid gland explants. Flow cytometry, immunocytochemistry, and gene arrays were performed to assess proliferation, standard mesenchymal stem cell, and putative SG epithelial stem/progenitor cell markers. Epithelial differentiation was induced and different SG-specific markers investigated. Functional assays upon neurostimulation determined α-amylase activity, trans-epithelial electrical resistance, and calcium influx. Primary cells exhibited SG epithelial progenitors and proliferation markers. After differentiation, SG markers were abundantly expressed resembling epithelial lineages (E-cadherin, Krt5, Krt14), and myoepithelial (α-smooth muscle actin) and neuronal (β3-tubulin, Chrm3) compartments. Differentiated cells from submandibular gland explant models displayed significantly greater proliferation, number of epithelial progenitors, amylase activity, and epithelial barrier function when compared to parotid gland models. Intracellular calcium was mobilized upon cholinergic and adrenergic neurostimulation. In summary, this study highlights new strategies to develop secretory epithelia from porcine SG explants, suitable for future proof-of-concept SG regeneration studies, as well as for testing novel muscarinic agonists and other biomolecules for dry mouth. Full article

(This article belongs to the Special Issue New Targets and Strategies in Regenerative Medicine)

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13 pages, 3222 KiB

Open AccessArticle

Elevated SH3BP5 Correlates with Poor Outcome and Contributes to the Growth of Acute Myeloid Leukemia Cells

by Minjing Li, Shiyu Hao, Chunling Li, Huimin Xiao, Liyuan Sun, Zhenhai Yu, Naili Zhang, Yanlian Xiong, Dongmei Zhao and Yancun Yin

Biomolecules 2019, 9(9), 505; https://doi.org/10.3390/biom9090505 - 19 Sep 2019

Cited by 7 | Viewed by 2741

Abstract

Current strategies are not especially successful in the treatment of acute myeloid leukemia (AML). The identification and characterization of oncogenes crucial to the survival and growth of leukemia cells will provide potential targets for the exploitation of novel therapies. Herein, we report that [...] Read more.

Current strategies are not especially successful in the treatment of acute myeloid leukemia (AML). The identification and characterization of oncogenes crucial to the survival and growth of leukemia cells will provide potential targets for the exploitation of novel therapies. Herein, we report that the elevated expression of SH3 domain-binding protein 5 (SH3BP5) significantly correlates with poor outcomes of AML patients. To test whether SH3BP5 contributes to the growth and survival of AML cells, we use the shRNA-encoding lentivirus system to achieve the knockdown of SH3BP5 expression in human AML cell lines U937, THP-1, Kasumi-1, and MV4-11. Functionally, the knockdown of SH3BP5 expression markedly inhibits the cell viability and induced apoptosis of these leukemia cells. Mechanistically, western blot analysis indicates that the knockdown of SH3BP5 expression decreases the phosphorylation of JNK and BAD. Moreover, the JNK agonist anisomycin rescues the growth inhibition phenotype of SH3BP5 deficiency in THP-1 cells. Moreover, the expression of SH3BP5 positively correlates with CD25 and CD123 levels. Finally, our study highlights the crucial role of SH3BP5 in promoting the survival of AML cells, and its suppression may be a potential therapeutic strategy for treating human AML. Full article

(This article belongs to the Special Issue New Targets and Strategies in Regenerative Medicine)

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14 pages, 5035 KiB

Open AccessArticle

Development and Optimization of the Novel Fabrication Method of Highly Macroporous Chitosan/Agarose/Nanohydroxyapatite Bone Scaffold for Potential Regenerative Medicine Applications

by Paulina Kazimierczak, Krzysztof Palka and Agata Przekora

Biomolecules 2019, 9(9), 434; https://doi.org/10.3390/biom9090434 - 01 Sep 2019

Cited by 26 | Viewed by 3100

Abstract

Bone scaffolds mimicking the three-dimensional bone structure are of essential importance for bone regeneration. The aim of this study was to develop and optimize the production method of highly macroporous bone scaffold composed of polysaccharide matrix (chitosan–agarose) reinforced with nanohydroxyapatite. The highly macroporous [...] Read more.

Bone scaffolds mimicking the three-dimensional bone structure are of essential importance for bone regeneration. The aim of this study was to develop and optimize the production method of highly macroporous bone scaffold composed of polysaccharide matrix (chitosan–agarose) reinforced with nanohydroxyapatite. The highly macroporous structure was obtained by the simultaneous application of a gas-foaming agent and freeze-drying technique. Fabricated variants of biomaterials (produced using different gas-foaming agent and solvent concentrations) were subjected to porosity evaluation and compression test in order to select the scaffold with the best properties. Then, bioactivity, cytotoxicity, and cell growth on the surface of the selected biomaterial were assessed. The obtained results showed that the simultaneous application of gas-foaming and freeze-drying methods allows for the production of biomaterials characterized by high total and open porosity. It was proved that the best porosity is obtained when solvent (CH₃COOH) and foaming agent (NaHCO₃) are applied at ratio 1:1. Nevertheless, the high porosity of novel biomaterial decreases its mechanical strength as determined by compression test. Importantly, novel scaffold is non-toxic to osteoblasts and favors cell attachment and growth on its surface. All mentioned properties make the novel biomaterial a promising candidate to be used in regenerative medicine in non-load bearing implantation sites. Full article

(This article belongs to the Special Issue New Targets and Strategies in Regenerative Medicine)

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Review

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34 pages, 7528 KiB

Open AccessEditor’s ChoiceReview

Molecular Mechanisms Contributing to Mesenchymal Stromal Cell Aging

by Simona Neri and Rosa Maria Borzì

Biomolecules 2020, 10(2), 340; https://doi.org/10.3390/biom10020340 - 21 Feb 2020

Cited by 70 | Viewed by 8642

Abstract

Mesenchymal stem/stromal cells (MSCs) are a reservoir for tissue homeostasis and repair that age during organismal aging. Beside the fundamental in vivo role of MSCs, they have also emerged in the last years as extremely promising therapeutic agents for a wide variety of [...] Read more.

Mesenchymal stem/stromal cells (MSCs) are a reservoir for tissue homeostasis and repair that age during organismal aging. Beside the fundamental in vivo role of MSCs, they have also emerged in the last years as extremely promising therapeutic agents for a wide variety of clinical conditions. MSC use frequently requires in vitro expansion, thus exposing cells to replicative senescence. Aging of MSCs (both in vivo and in vitro) can affect not only their replicative potential, but also their properties, like immunomodulation and secretory profile, thus possibly compromising their therapeutic effect. It is therefore of critical importance to unveil the underlying mechanisms of MSC senescence and to define shared methods to assess MSC aging status. The present review will focus on current scientific knowledge about MSC aging mechanisms, control and effects, including possible anti-aging treatments. Full article

(This article belongs to the Special Issue New Targets and Strategies in Regenerative Medicine)

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23 pages, 1724 KiB

Open AccessReview

Engineering Extracellular Vesicles as Nanotherapeutics for Regenerative Medicine

by Lalithasri Ramasubramanian, Priyadarsini Kumar and Aijun Wang

Biomolecules 2020, 10(1), 48; https://doi.org/10.3390/biom10010048 - 28 Dec 2019

Cited by 74 | Viewed by 7186

Abstract

Long thought of to be vesicles that primarily recycled waste biomolecules from cells, extracellular vesicles (EVs) have now emerged as a new class of nanotherapeutics for regenerative medicine. Recent studies have proven their potential as mediators of cell proliferation, immunomodulation, extracellular matrix organization [...] Read more.

Long thought of to be vesicles that primarily recycled waste biomolecules from cells, extracellular vesicles (EVs) have now emerged as a new class of nanotherapeutics for regenerative medicine. Recent studies have proven their potential as mediators of cell proliferation, immunomodulation, extracellular matrix organization and angiogenesis, and are currently being used as treatments for a variety of diseases and injuries. They are now being used in combination with a variety of more traditional biomaterials and tissue engineering strategies to stimulate tissue repair and wound healing. However, the clinical translation of EVs has been greatly slowed due to difficulties in EV isolation and purification, as well as their limited yields and functional heterogeneity. Thus, a field of EV engineering has emerged in order to augment the natural properties of EVs and to recapitulate their function in semi-synthetic and synthetic EVs. Here, we have reviewed current technologies and techniques in this growing field of EV engineering while highlighting possible future applications for regenerative medicine. Full article

(This article belongs to the Special Issue New Targets and Strategies in Regenerative Medicine)

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26 pages, 4264 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Polysaccharide-Based Systems for Targeted Stem Cell Differentiation and Bone Regeneration

by Markus Witzler, Dominik Büchner, Sarah Hani Shoushrah, Patrick Babczyk, Juliana Baranova, Steffen Witzleben, Edda Tobiasch and Margit Schulze

Biomolecules 2019, 9(12), 840; https://doi.org/10.3390/biom9120840 - 06 Dec 2019

Cited by 34 | Viewed by 5907

Abstract

Bone tissue engineering is an ever-changing, rapidly evolving, and highly interdisciplinary field of study, where scientists try to mimic natural bone structure as closely as possible in order to facilitate bone healing. New insights from cell biology, specifically from mesenchymal stem cell differentiation [...] Read more.

Bone tissue engineering is an ever-changing, rapidly evolving, and highly interdisciplinary field of study, where scientists try to mimic natural bone structure as closely as possible in order to facilitate bone healing. New insights from cell biology, specifically from mesenchymal stem cell differentiation and signaling, lead to new approaches in bone regeneration. Novel scaffold and drug release materials based on polysaccharides gain increasing attention due to their wide availability and good biocompatibility to be used as hydrogels and/or hybrid components for drug release and tissue engineering. This article reviews the current state of the art, recent developments, and future perspectives in polysaccharide-based systems used for bone regeneration. Full article

(This article belongs to the Special Issue New Targets and Strategies in Regenerative Medicine)

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25 pages, 1954 KiB

Open AccessReview

A Hepatic Scaffold from Decellularized Liver Tissue: Food for Thought

by Stefania Croce, Andrea Peloso, Tamara Zoro, Maria Antonietta Avanzini and Lorenzo Cobianchi

Biomolecules 2019, 9(12), 813; https://doi.org/10.3390/biom9120813 - 02 Dec 2019

Cited by 46 | Viewed by 6835

Abstract

Allogeneic liver transplantation is still deemed the gold standard solution for end-stage organ failure; however, donor organ shortages have led to extended waiting lists for organ transplants. In order to overcome the lack of donors, the development of new therapeutic options is mandatory. [...] Read more.

Allogeneic liver transplantation is still deemed the gold standard solution for end-stage organ failure; however, donor organ shortages have led to extended waiting lists for organ transplants. In order to overcome the lack of donors, the development of new therapeutic options is mandatory. In the last several years, organ bioengineering has been extensively explored to provide transplantable tissues or whole organs with the final goal of creating a three-dimensional growth microenvironment mimicking the native structure. It has been frequently reported that an extracellular matrix-based scaffold offers a structural support and important biological molecules that could help cellular proliferation during the recellularization process. The aim of the present review is to underline the recent developments in cell-on-scaffold technology for liver bioengineering, taking into account: (1) biological and synthetic scaffolds; (2) animal and human tissue decellularization; (3) scaffold recellularization; (4) 3D bioprinting; and (5) organoid technology. Future possible clinical applications in regenerative medicine for liver tissue engineering and for drug testing were underlined and dissected. Full article

(This article belongs to the Special Issue New Targets and Strategies in Regenerative Medicine)

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24 pages, 3892 KiB

Open AccessEditor’s ChoiceReview

Biomaterials for In Situ Tissue Regeneration: A Review

by Saba Abdulghani and Geoffrey R. Mitchell

Biomolecules 2019, 9(11), 750; https://doi.org/10.3390/biom9110750 - 19 Nov 2019

Cited by 138 | Viewed by 12540

Abstract

This review focuses on a somewhat unexplored strand of regenerative medicine, that is in situ tissue engineering. In this approach manufactured scaffolds are implanted in the injured region for regeneration within the patient. The scaffold is designed to attract cells to the required [...] Read more.

This review focuses on a somewhat unexplored strand of regenerative medicine, that is in situ tissue engineering. In this approach manufactured scaffolds are implanted in the injured region for regeneration within the patient. The scaffold is designed to attract cells to the required volume of regeneration to subsequently proliferate, differentiate, and as a consequence develop tissue within the scaffold which in time will degrade leaving just the regenerated tissue. This review highlights the wealth of information available from studies of ex-situ tissue engineering about the selection of materials for scaffolds. It is clear that there are great opportunities for the use of additive manufacturing to prepare complex personalized scaffolds and we speculate that by building on this knowledge and technology, the development of in situ tissue engineering could rapidly increase. Ex-situ tissue engineering is handicapped by the need to develop the tissue in a bioreactor where the conditions, however optimized, may not be optimum for accelerated growth and maintenance of the cell function. We identify that in both methodologies the prospect of tissue regeneration has created much promise but delivered little outside the scope of laboratory-based experiments. We propose that the design of the scaffolds and the materials selected remain at the heart of developments in this field and there is a clear need for predictive modelling which can be used in the design and optimization of materials and scaffolds. Full article

(This article belongs to the Special Issue New Targets and Strategies in Regenerative Medicine)

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40 pages, 2325 KiB

Open AccessReview

Status of Plant Protein-Based Green Scaffolds for Regenerative Medicine Applications

by Hossein Jahangirian, Susan Azizi, Roshanak Rafiee-Moghaddam, Bahram Baratvand and Thomas J. Webster

Biomolecules 2019, 9(10), 619; https://doi.org/10.3390/biom9100619 - 17 Oct 2019

Cited by 40 | Viewed by 6752

Abstract

In recent decades, regenerative medicine has merited substantial attention from scientific and research communities. One of the essential requirements for this new strategy in medicine is the production of biocompatible and biodegradable scaffolds with desirable geometric structures and mechanical properties. Despite such promise, [...] Read more.

In recent decades, regenerative medicine has merited substantial attention from scientific and research communities. One of the essential requirements for this new strategy in medicine is the production of biocompatible and biodegradable scaffolds with desirable geometric structures and mechanical properties. Despite such promise, it appears that regenerative medicine is the last field to embrace green, or environmentally-friendly, processes, as many traditional tissue engineering materials employ toxic solvents and polymers that are clearly not environmentally friendly. Scaffolds fabricated from plant proteins (for example, zein, soy protein, and wheat gluten), possess proper mechanical properties, remarkable biocompatibility and aqueous stability which make them appropriate green biomaterials for regenerative medicine applications. The use of plant-derived proteins in regenerative medicine has been especially inspired by green medicine, which is the use of environmentally friendly materials in medicine. In the current review paper, the literature is reviewed and summarized for the applicability of plant proteins as biopolymer materials for several green regenerative medicine and tissue engineering applications. Full article

(This article belongs to the Special Issue New Targets and Strategies in Regenerative Medicine)

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16 pages, 886 KiB

Open AccessReview

Progress in the Development of Chitosan-Based Biomaterials for Tissue Engineering and Regenerative Medicine

by Bolat Sultankulov, Dmitriy Berillo, Karina Sultankulova, Tursonjan Tokay and Arman Saparov

Biomolecules 2019, 9(9), 470; https://doi.org/10.3390/biom9090470 - 10 Sep 2019

Cited by 212 | Viewed by 8957

Abstract

Over the last few decades, chitosan has become a good candidate for tissue engineering applications. Derived from chitin, chitosan is a unique natural polysaccharide with outstanding properties in line with excellent biodegradability, biocompatibility, and antimicrobial activity. Due to the presence of free amine [...] Read more.

Over the last few decades, chitosan has become a good candidate for tissue engineering applications. Derived from chitin, chitosan is a unique natural polysaccharide with outstanding properties in line with excellent biodegradability, biocompatibility, and antimicrobial activity. Due to the presence of free amine groups in its backbone chain, chitosan could be further chemically modified to possess additional functional properties useful for the development of different biomaterials in regenerative medicine. In the current review, we will highlight the progress made in the development of chitosan-containing bioscaffolds, such as gels, sponges, films, and fibers, and their possible applications in tissue repair and regeneration, as well as the use of chitosan as a component for drug delivery applications. Full article

(This article belongs to the Special Issue New Targets and Strategies in Regenerative Medicine)

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56 pages, 5838 KiB

Open AccessReview

Electrically Conductive Materials: Opportunities and Challenges in Tissue Engineering

by Azadeh Saberi, Farzaneh Jabbari, Payam Zarrintaj, Mohammad Reza Saeb and Masoud Mozafari

Biomolecules 2019, 9(9), 448; https://doi.org/10.3390/biom9090448 - 04 Sep 2019

Cited by 146 | Viewed by 9282

Abstract

Tissue engineering endeavors to regenerate tissues and organs through appropriate cellular and molecular interactions at biological interfaces. To this aim, bio-mimicking scaffolds have been designed and practiced to regenerate and repair dysfunctional tissues by modifying cellular activity. Cellular activity and intracellular signaling are [...] Read more.

Tissue engineering endeavors to regenerate tissues and organs through appropriate cellular and molecular interactions at biological interfaces. To this aim, bio-mimicking scaffolds have been designed and practiced to regenerate and repair dysfunctional tissues by modifying cellular activity. Cellular activity and intracellular signaling are performances given to a tissue as a result of the function of elaborated electrically conductive materials. In some cases, conductive materials have exhibited antibacterial properties; moreover, such materials can be utilized for on-demand drug release. Various types of materials ranging from polymers to ceramics and metals have been utilized as parts of conductive tissue engineering scaffolds, having conductivity assortments from a range of semi-conductive to conductive. The cellular and molecular activity can also be affected by the microstructure; therefore, the fabrication methods should be evaluated along with an appropriate selection of conductive materials. This review aims to address the research progress toward the use of electrically conductive materials for the modulation of cellular response at the material-tissue interface for tissue engineering applications. Full article

(This article belongs to the Special Issue New Targets and Strategies in Regenerative Medicine)

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