International Journal of Molecular Sciences

Research

16 pages, 3402 KiB

Open AccessArticle

Impact of Periprosthetic Fibroblast-Like Cells on Osteoclastogenesis in Co-Culture with Peripheral Blood Mononuclear Cells Varies Depending on Culture System

by Miriam I. Koehler, Eliza S. Hartmann, Sabine Schluessel, Felicitas Beck, Julia I. Redeker, Baerbel Schmitt, Marina Unger, Martijn van Griensven, Burkhard Summer, Andreas Fottner and Susanne Mayer-Wagner

Int. J. Mol. Sci. 2019, 20(10), 2583; https://doi.org/10.3390/ijms20102583 - 26 May 2019

Cited by 6 | Viewed by 4284

Abstract

Co-culture studies investigating the role of periprosthetic fibroblasts (PPFs) in inflammatory osteoclastogenesis reveal contrary results, partly showing an osteoprotective function of fibroblasts and high OPG expression in monolayer. These data disagree with molecular analyses of original periosteolytic tissues. In order to find a [...] Read more.

Co-culture studies investigating the role of periprosthetic fibroblasts (PPFs) in inflammatory osteoclastogenesis reveal contrary results, partly showing an osteoprotective function of fibroblasts and high OPG expression in monolayer. These data disagree with molecular analyses of original periosteolytic tissues. In order to find a more reliable model, PPFs were co-cultivated with peripheral blood mononuclear cells (PBMCs) in a transwell system and compared to conventional monolayer cultures. The gene expression of key regulators of osteoclastogenesis (macrophage colony-stimulating factor (MCSF), receptor activator of NF-κB ligand (RANK-L), osteoprotegerin (OPG), and tumor necrosis factor alpha (TNFα)) as well as the ability of bone resorption were analyzed. In monolayer co-cultures, PPFs executed an osteoprotective function with high OPG-expression, low RANK-L/OPG ratios, and a resulting inhibition of osteolysis even in the presence of MCSF and RANK-L. For transwell co-cultures, profound changes in gene expression, with a more than hundredfold decrease of OPG and a significant upregulation of TNFα were observed. In conclusion, we were able to show that a change of culture conditions towards a transwell system resulted in a considerably more osteoclastogenic gene expression profile, being closer to findings in original periosteolytic tissues. This study therefore presents an interesting approach for a more reliable in vitro model to examine the role of fibroblasts in periprosthetic osteoclastogenesis in the future. Full article

(This article belongs to the Special Issue Biomaterials for Musculoskeletal System)

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23 pages, 10633 KiB

Open AccessArticle

Development, Characterization and In Vitro Biological Properties of Scaffolds Fabricated From Calcium Phosphate Nanoparticles

by Lizette Morejón, José Angel Delgado, Alexandre Antunes Ribeiro, Marize Varella de Oliveira, Eduardo Mendizábal, Ibrahim García, Adrián Alfonso, Patrina Poh, Martijn van Griensven and Elizabeth R. Balmayor

Int. J. Mol. Sci. 2019, 20(7), 1790; https://doi.org/10.3390/ijms20071790 - 11 Apr 2019

Cited by 39 | Viewed by 4806

Abstract

Ceramic materials mimic the mineral composition of native bone and feature osteoconductive properties; they are therefore used to regenerate bone tissue. Much research focuses on increasing the porosity and pore interconnectivity of ceramic scaffolds to increase osteoconductivity, cell migration and cell-cell interaction. We [...] Read more.

Ceramic materials mimic the mineral composition of native bone and feature osteoconductive properties; they are therefore used to regenerate bone tissue. Much research focuses on increasing the porosity and pore interconnectivity of ceramic scaffolds to increase osteoconductivity, cell migration and cell-cell interaction. We aimed to fabricate biocompatible 3D-scaffolds featuring macro- and microporous calcium phosphates with high pore interconnection. Nanoparticles of hydroxyapatite (HA) and calcium deficient hydroxyapatite (CDHA) were synthesized by wet chemical precipitation. Scaffolds were produced from them by the replication polymeric foam technique. Solid content and sintering temperature were varied. Nanoparticles and scaffolds were characterized regarding morphology, chemical and mineral composition, porosity and mechanical properties. Biocompatibility, cell attachment and distribution were evaluated in vitro with human adipose mesenchymal stem cells. Scaffolds with total porosity of 71%–87%, pores in the range of 280–550 µm and connectivity density up to 43 mm⁻³ were obtained. Smaller pore sizes were obtained at higher sintering temperature. High solid content resulted in a decrease of total porosity but increased interconnectivity. Scaffolds 50HA/50β-TCP featured superior interconnectivity and mechanical properties. They were bioactive and biocompatible. High HA solid content (40 wt.%) in the HA pure scaffolds was negative for cell viability and proliferation, while in the 50HA/50β-TCP composite scaffolds it resulted more biocompatible. Full article

(This article belongs to the Special Issue Biomaterials for Musculoskeletal System)

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19 pages, 4121 KiB

Open AccessArticle

Exogenous Delivery of Link N mRNA into Chondrocytes and MSCs—The Potential Role in Increasing Anabolic Response

by Gauri Tendulkar, Sabrina Ehnert, Vrinda Sreekumar, Tao Chen, Hans-Peter Kaps, Sonia Golombek, Hans-Peter Wendel, Andreas K. Nüssler and Meltem Avci-Adali

Int. J. Mol. Sci. 2019, 20(7), 1716; https://doi.org/10.3390/ijms20071716 - 6 Apr 2019

Cited by 9 | Viewed by 4711

Abstract

Musculoskeletal disorders, such as osteoarthritis and intervertebral disc degeneration are causes of morbidity, which concomitantly burdens the health and social care systems worldwide, with massive costs. Link N peptide has recently been described as a novel anabolic stimulator for intervertebral disc repair. In [...] Read more.

Musculoskeletal disorders, such as osteoarthritis and intervertebral disc degeneration are causes of morbidity, which concomitantly burdens the health and social care systems worldwide, with massive costs. Link N peptide has recently been described as a novel anabolic stimulator for intervertebral disc repair. In this study, we analyzed the influence on anabolic response, by delivering synthetic Link N encoding mRNA into primary human chondrocytes and mesenchymal stromal cells (SCP1 cells). Furthermore, both cell types were seeded on knitted titanium scaffolds, and the influence of Link N peptide mRNA for possible tissue engineering applications was investigated. Synthetic modified Link N mRNA was efficiently delivered into both cell types and cell transfection resulted in an enhanced expression of aggrecan, Sox 9, and type II collagen with a decreased expression of type X collagen. Interestingly, despite increased expression of BMP2 and BMP7, BMP signaling was repressed and TGFβ signaling was boosted by Link N transfection in mesenchymal stromal cells, suggesting possible regulatory mechanisms. Thus, the exogenous delivery of Link N peptide mRNA into cells augmented an anabolic response and thereby increased extracellular matrix synthesis. Considering these findings, we suppose that the cultivation of cells on knitted titanium scaffolds and the exogenous delivery of Link N peptide mRNA into cells could mechanically support the stability of tissue-engineered constructs and improve the synthesis of extracellular matrix by seeded cells. This method can provide a potent strategy for articular cartilage and intervertebral disc regeneration. Full article

(This article belongs to the Special Issue Biomaterials for Musculoskeletal System)

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13 pages, 2163 KiB

Open AccessArticle

A Dual Molecular Biointerface Combining RGD and KRSR Sequences Improves Osteoblastic Functions by Synergizing Integrin and Cell-Membrane Proteoglycan Binding

by Mireia Hoyos-Nogués, Elena Falgueras-Batlle, Maria-Pau Ginebra, José María Manero, Javier Gil and Carlos Mas-Moruno

Int. J. Mol. Sci. 2019, 20(6), 1429; https://doi.org/10.3390/ijms20061429 - 21 Mar 2019

Cited by 27 | Viewed by 4468

Abstract

Synergizing integrin and cell-membrane heparan sulfate proteoglycan signaling on biomaterials through peptidic sequences is known to have beneficial effects in the attachment and behavior of osteoblasts; however, controlling the exact amount and ratio of peptides tethered on a surface is challenging. Here, we [...] Read more.

Synergizing integrin and cell-membrane heparan sulfate proteoglycan signaling on biomaterials through peptidic sequences is known to have beneficial effects in the attachment and behavior of osteoblasts; however, controlling the exact amount and ratio of peptides tethered on a surface is challenging. Here, we present a dual molecular-based biointerface combining integrin (RGD) and heparin (KRSR)-binding peptides in a chemically controlled fashion. To this end, a tailor-made synthetic platform (PLATF) was designed and synthesized by solid-phase methodologies. The PLATF and the control linear peptides (RGD or KRSR) were covalently bound to titanium via silanization. Physicochemical characterization by means of contact angle, Raman spectroscopy and XPS proved the successful and stable grafting of the molecules. The biological potential of the biointerfaces was measured with osteoblastic (Saos-2) cells both at short and long incubation periods. Biomolecule grafting (either the PLATF, RGD or KRSR) statistically improved (p < 0.05) cell attachment, spreading, proliferation and mineralization, compared to control titanium. Moreover, the molecular PLATF biointerface synergistically enhanced mineralization (p < 0.05) of Saos-2 cells compared to RGD or KRSR alone. These results indicate that dual-function coatings may serve to improve the bioactivity of medical implants by mimicking synergistic receptor binding. Full article

(This article belongs to the Special Issue Biomaterials for Musculoskeletal System)

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14 pages, 6215 KiB

Open AccessArticle

Bone Marrow Aspirate Concentrate for the Treatment of Avascular Meniscus Tears in a One-Step Procedure—Evaluation of an In Vivo Model

by Matthias Koch, Selma Hammer, Julian Fuellerer, Siegmund Lang, Christian G. Pfeifer, Girish Pattappa, Johannes Weber, Markus Loibl, Michael Nerlich, Peter Angele and Johannes Zellner

Int. J. Mol. Sci. 2019, 20(5), 1120; https://doi.org/10.3390/ijms20051120 - 5 Mar 2019

Cited by 36 | Viewed by 5143

Abstract

Avascular meniscus tears show poor intrinsic regenerative potential. Thus, lesions within this area predispose the patient to developing knee osteoarthritis. Current research focuses on regenerative approaches using growth factors or mesenchymal stem cells (MSCs) to enhance healing capacity within the avascular meniscus zone. [...] Read more.

Avascular meniscus tears show poor intrinsic regenerative potential. Thus, lesions within this area predispose the patient to developing knee osteoarthritis. Current research focuses on regenerative approaches using growth factors or mesenchymal stem cells (MSCs) to enhance healing capacity within the avascular meniscus zone. The use of MSCs especially as progenitor cells and a source of growth factors has shown promising results. However, present studies use bone-marrow-derived BMSCs in a two-step procedure, which is limiting the transfer in clinical praxis. So, the aim of this study was to evaluate a one-step procedure using bone marrow aspirate concentrate (BMAC), containing BMSCs, for inducing the regeneration of avascular meniscus lesions. Longitudinal meniscus tears of 4 mm in size of the lateral New Zealand White rabbit meniscus were treated with clotted autologous PRP (platelet-rich plasma) or BMAC and a meniscus suture or a meniscus suture alone. Menisci were harvested at 6 and 12 weeks after initial surgery. Macroscopical and histological evaluation was performed according to an established Meniscus Scoring System. BMAC significantly enhanced regeneration of the meniscus lesions in a time-dependent manner and in comparison to the PRP and control groups, where no healing could be observed. Treatment of avascular meniscus lesions with BMAC and meniscus suturing seems to be a promising approach to promote meniscus regeneration in the avascular zone using a one-step procedure. Full article

(This article belongs to the Special Issue Biomaterials for Musculoskeletal System)

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12 pages, 4070 KiB

Open AccessArticle

A Growth Factor-Free Co-Culture System of Osteoblasts and Peripheral Blood Mononuclear Cells for the Evaluation of the Osteogenesis Potential of Melt-Electrowritten Polycaprolactone Scaffolds

by Andreas Hammerl, Carlos E. Diaz Cano, Elena M. De-Juan-Pardo, Martijn van Griensven and Patrina S.P. Poh

Int. J. Mol. Sci. 2019, 20(5), 1068; https://doi.org/10.3390/ijms20051068 - 1 Mar 2019

Cited by 23 | Viewed by 3880

Abstract

Scaffolds made of biodegradable biomaterials are widely used to guide bone regeneration. Commonly, in vitro assessment of scaffolds’ osteogenesis potential has been performed predominantly in monoculture settings. Hence, this study evaluated the potential of an unstimulated, growth factor-free co-culture system comprised of osteoblasts [...] Read more.

Scaffolds made of biodegradable biomaterials are widely used to guide bone regeneration. Commonly, in vitro assessment of scaffolds’ osteogenesis potential has been performed predominantly in monoculture settings. Hence, this study evaluated the potential of an unstimulated, growth factor-free co-culture system comprised of osteoblasts (OB) and peripheral blood mononuclear cells (PBMC) over monoculture of OB as an in vitro platform for screening of bone regeneration potential of scaffolds. Particularly, this study focuses on the osteogenic differentiation and mineralized matrix formation aspects of cells. The study was performed using scaffolds fabricated by means of a melt electrowriting (MEW) technique made of medical-grade polycaprolactone (PCL), with or without a surface coating of calcium phosphate (CaP). Qualitative results, i.e., cell morphology by fluorescence imaging and matrix mineralization by von Kossa staining, indicated the differences in cell behaviours in response to scaffolds’ biomaterial. However, no obvious differences were noted between OB and OB+PBMC groups. Hence, quantitative investigation, i.e., alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) activities, and gene expression were quantitatively evaluated by reverse transcription-polymerase chain reaction (RT-qPCR), were evaluated only of PCL/CaP scaffolds cultured with OB+PBMC, while PCL/CaP scaffolds cultured with OB or PBMC acted as a control. Although this study showed no differences in terms of osteogenic differentiation and ECM mineralization, preliminary qualitative results indicate an obvious difference in the cell/non-mineralized ECM density between scaffolds cultured with OB or OB+PBMC that could be worth further investigation. Collectively, the unstimulated, growth factor-free co-culture (OB+PBMC) system presented in this study could be beneficial for the pre-screening of scaffolds’ in vitro bone regeneration potential prior to validation in vivo. Full article

(This article belongs to the Special Issue Biomaterials for Musculoskeletal System)

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12 pages, 2595 KiB

Open AccessArticle

Immobilization of Denosumab on Titanium Affects Osteoclastogenesis of Human Peripheral Blood Monocytes

by Felicitas Beck, Eliza S. Hartmann, Miriam I. Koehler, Julia I. Redeker, Sabine Schluessel, Baerbel Schmitt, Andreas Fottner, Marina Unger, Martijn van Griensven, Jan Michael, Burkhard Summer, Karl-Heinz Kunzelmann, Rene Beutner, Dieter Scharnweber, Paul J. Kostenuik and Susanne Mayer-Wagner

Int. J. Mol. Sci. 2019, 20(5), 1002; https://doi.org/10.3390/ijms20051002 - 26 Feb 2019

Cited by 7 | Viewed by 3920

Abstract

Immobilization of proteins has been examined to improve implant surfaces. In this study, titanium surfaces were modified with nanofunctionalized denosumab (cDMAB), a human monoclonal anti-RANKL IgG. Noncoding DNA oligonucleotides (ODN) served as linker molecules between titanium and DMAB. Binding and release experiments demonstrated [...] Read more.

Immobilization of proteins has been examined to improve implant surfaces. In this study, titanium surfaces were modified with nanofunctionalized denosumab (cDMAB), a human monoclonal anti-RANKL IgG. Noncoding DNA oligonucleotides (ODN) served as linker molecules between titanium and DMAB. Binding and release experiments demonstrated a high binding capacity of cDMAB and continuous release. Human peripheral mononuclear blood cells (PBMCs) were cultured in the presence of RANKL/MCSF for 28 days and differentiated into osteoclasts. Adding soluble DMAB to the medium inhibited osteoclast differentiation. On nanofunctionalized titanium specimens, the osteoclast-specific TRAP5b protein was monitored and showed a significantly decreased amount on cDMAB-titanium in PBMCs + RANKL/MCSF. PBMCs on cDMAB-titanium also changed SEM cell morphology. In conclusion, the results indicate that cDMAB reduces osteoclast formation and has the potential to reduce osteoclastogenesis on titanium surfaces. Full article

(This article belongs to the Special Issue Biomaterials for Musculoskeletal System)

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21 pages, 10090 KiB

Open AccessArticle

Osteochondral Tissue Regeneration Using a Tyramine-Modified Bilayered PLGA Scaffold Combined with Articular Chondrocytes in a Porcine Model

by Tzu-Hsiang Lin, Hsueh-Chun Wang, Wen-Hui Cheng, Horng-Chaung Hsu and Ming-Long Yeh

Int. J. Mol. Sci. 2019, 20(2), 326; https://doi.org/10.3390/ijms20020326 - 15 Jan 2019

Cited by 36 | Viewed by 5734

Abstract

Repairing damaged articular cartilage is challenging due to the limited regenerative capacity of hyaline cartilage. In this study, we fabricated a bilayered poly (lactic-co-glycolic acid) (PLGA) scaffold with small (200–300 μm) and large (200–500 μm) pores by salt leaching to stimulate chondrocyte differentiation, [...] Read more.

Repairing damaged articular cartilage is challenging due to the limited regenerative capacity of hyaline cartilage. In this study, we fabricated a bilayered poly (lactic-co-glycolic acid) (PLGA) scaffold with small (200–300 μm) and large (200–500 μm) pores by salt leaching to stimulate chondrocyte differentiation, cartilage formation, and endochondral ossification. The scaffold surface was treated with tyramine to promote scaffold integration into native tissue. Porcine chondrocytes retained a round shape during differentiation when grown on the small pore size scaffold, and had a fibroblast-like morphology during transdifferentiation in the large pore size scaffold after five days of culture. Tyramine-treated scaffolds with mixed pore sizes seeded with chondrocytes were pressed into three-mm porcine osteochondral defects; tyramine treatment enhanced the adhesion of the small pore size scaffold to osteochondral tissue and increased glycosaminoglycan and collagen type II (Col II) contents, while reducing collagen type X (Col X) production in the cartilage layer. Col X content was higher for scaffolds with a large pore size, which was accompanied by the enhanced generation of subchondral bone. Thus, chondrocytes seeded in tyramine-treated bilayered scaffolds with small and large pores in the upper and lower parts, respectively, can promote osteochondral regeneration and integration for articular cartilage repair. Full article

(This article belongs to the Special Issue Biomaterials for Musculoskeletal System)

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10 pages, 2984 KiB

Open AccessArticle

Selenium-Enriched Brushite: A Novel Biomaterial for Potential Use in Bone Tissue Engineering

by Aleksandra Laskus, Anna Zgadzaj and Joanna Kolmas

Int. J. Mol. Sci. 2018, 19(12), 4042; https://doi.org/10.3390/ijms19124042 - 14 Dec 2018

Cited by 9 | Viewed by 3150

Abstract

In this study, a novel biomaterial, i.e., brushite containing 0.67 wt% of selenium (Se-Bru) was synthesized via a wet precipitation method. Pure, unsubstituted brushite (Bru) was synthesized via the same method and used as a reference material. Different techniques of instrumental analysis were [...] Read more.

In this study, a novel biomaterial, i.e., brushite containing 0.67 wt% of selenium (Se-Bru) was synthesized via a wet precipitation method. Pure, unsubstituted brushite (Bru) was synthesized via the same method and used as a reference material. Different techniques of instrumental analysis were applied to investigate and compare physicochemical properties of both materials. Fourier-Transform Infrared Spectroscopy confirmed the chemical identity of both materials. Scanning Electron Microscopy (SEM) was used to study the morphology and indicated that both samples (Bru and Se-Bru) consisted of plate-like microcrystals. Powder X-ray Diffraction (PXRD) showed that Bru, as well as Se-Bru were crystallographically homogenous. What is more, the data obtained from PXRD studies revealed that the substitution of selenite ions into the crystal structure of the material had clearly affected its lattice parameters. The incorporation of selenium was also confirmed by solid-state ¹H→³¹P CP MAS kinetics experiments. Additionally, studies on the release kinetics of the elements forming Se-Bru and preliminary cytotoxicity tests were conducted. This preliminary research will favor a better understanding of ionic substitution in calcium phosphates and may be a starting point for the development of selenium-doped brushite cements for potential use in bone tissue impairments treatment. Full article

(This article belongs to the Special Issue Biomaterials for Musculoskeletal System)

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16 pages, 1763 KiB

Open AccessArticle

Biocompatibility and Biological Efficiency of Inorganic Calcium Filled Bacterial Cellulose Based Hydrogel Scaffolds for Bone Bioengineering

by Probal Basu, Nabanita Saha, Radostina Alexandrova, Boyka Andonova-Lilova, Milena Georgieva, George Miloshev and Petr Saha

Int. J. Mol. Sci. 2018, 19(12), 3980; https://doi.org/10.3390/ijms19123980 - 11 Dec 2018

Cited by 40 | Viewed by 5678

Abstract

The principal focus of this work is the in-depth analysis of the biological efficiency of inorganic calcium-filled bacterial cellulose (BC) based hydrogel scaffolds for their future use in bone tissue engineering/bioengineering. Inorganic calcium was filled in the form of calcium phosphate (β-tri calcium [...] Read more.

The principal focus of this work is the in-depth analysis of the biological efficiency of inorganic calcium-filled bacterial cellulose (BC) based hydrogel scaffolds for their future use in bone tissue engineering/bioengineering. Inorganic calcium was filled in the form of calcium phosphate (β-tri calcium phosphate (β-TCP) and hydroxyapatite (HA)) and calcium carbonate (CaCO₃). The additional calcium, CaCO₃ was incorporated following in vitro bio-mineralization. Cell viability study was performed with the extracts of BC based hydrogel scaffolds: BC-PVP, BC-CMC; BC-PVP-β-TCP/HA, BC-CMC-β-TCP/HA and BC-PVP-β-TCP/HA-CaCO₃, BC-CMC-β-TCP/HA-CaCO₃; respectively. The biocompatibility study was performed with two different cell lines, i.e., human fibroblasts, Lep-3 and mouse bone explant cells. Each hydrogel scaffold has facilitated notable growth and proliferation in presence of these two cell types. Nevertheless, the percentage of DNA strand breaks was higher when cells were treated with BC-CMC based scaffolds i.e., BC-CMC-β-TCP/HA and BC-CMC-β-TCP/HA-CaCO₃. On the other hand, the apoptosis of human fibroblasts, Lep-3 was insignificant in BC-PVP-β-TCP/HA. The scanning electron microscopy confirmed the efficient adhesion and growth of Lep-3 cells throughout the surface of BC-PVP and BC-PVP-β-TCP/HA. Hence, among all inorganic calcium filled hydrogel scaffolds, ‘BC-PVP-β-TCP/HA’ was recommended as an efficient tissue engineering scaffold which could facilitate the musculoskeletal (i.e., bone tissue) engineering/bioengineering. Full article

(This article belongs to the Special Issue Biomaterials for Musculoskeletal System)

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13 pages, 1944 KiB

Open AccessArticle

Combining Calcium Phosphates with Polysaccharides: A Bone-Inspired Material Modulating Monocyte/Macrophage Early Inflammatory Response

by Hassan Rammal, Camille Bour, Marie Dubus, Laura Entz, Léa Aubert, Sophie C. Gangloff, Sandra Audonnet, Nicolae B. Bercu, Fouzia Boulmedais, Cedric Mauprivez and Halima Kerdjoudj

Int. J. Mol. Sci. 2018, 19(11), 3458; https://doi.org/10.3390/ijms19113458 - 3 Nov 2018

Cited by 9 | Viewed by 4788

Abstract

The use of inorganic calcium/phosphate supplemented with biopolymers has drawn lots of attention in bone regenerative medicine. While inflammation is required for bone healing, its exacerbation alters tissue regeneration/implants integration. Inspired by bone composition, a friendly automated spray-assisted system was used to build [...] Read more.

The use of inorganic calcium/phosphate supplemented with biopolymers has drawn lots of attention in bone regenerative medicine. While inflammation is required for bone healing, its exacerbation alters tissue regeneration/implants integration. Inspired by bone composition, a friendly automated spray-assisted system was used to build bioactive and osteoinductive calcium phosphate/chitosan/hyaluronic acid substrate (CaP-CHI-HA). Exposing monocytes to CaP-CHI-HA resulted in a secretion of pro-healing VEGF and TGF-β growth factors, TNF-α, MCP-1, IL-6 and IL-8 pro-inflammatory mediators but also IL-10 anti-inflammatory cytokine along with an inflammatory index below 1.5 (versus 2.5 and 7.5 following CaP and LPS stimulation, respectively). Although CD44 hyaluronic acid receptor seems not to be involved in the inflammatory regulation, results suggest a potential role of chemical composition and calcium release from build-up substrates, in affecting the intracellular expression of a calcium-sensing receptor. Herein, our findings indicate a great potential of CaP-CHI-HA in providing required inflammation-healing balance, favorable for bone healing/regeneration. Full article

(This article belongs to the Special Issue Biomaterials for Musculoskeletal System)

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Review

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13 pages, 4256 KiB

Open AccessReview

Biomaterials for Cleft Lip and Palate Regeneration

by Marcela Martín-del-Campo, Raúl Rosales-Ibañez and Luis Rojo

Int. J. Mol. Sci. 2019, 20(9), 2176; https://doi.org/10.3390/ijms20092176 - 2 May 2019

Cited by 36 | Viewed by 8961

Abstract

Craniofacial bone defect anomalies affect both soft and hard tissues and can be caused by trauma, bone recessions from tumors and cysts, or even from congenital disorders. On this note, cleft/lip palate is the most prevalent congenital craniofacial defect caused by disturbed embryonic [...] Read more.

Craniofacial bone defect anomalies affect both soft and hard tissues and can be caused by trauma, bone recessions from tumors and cysts, or even from congenital disorders. On this note, cleft/lip palate is the most prevalent congenital craniofacial defect caused by disturbed embryonic development of soft and hard tissues around the oral cavity and face area, resulting in most cases, of severe limitations with chewing, swallowing, and talking as well as problems of insufficient space for teeth, proper breathing, and self-esteem problems as a consequence of facial appearance. Spectacular advances in regenerative medicine have arrived, giving new hope to patients that can benefit from new tissue engineering therapies based on the supportive action of 3D biomaterials together with the synergic action of osteo-inductive molecules and recruited stem cells that can be driven to the process of bone regeneration. However, few studies have focused on the application of tissue engineering to the regeneration of the cleft/lip and only a few have reported significant advances to offer real clinical solutions. This review provides an updated and deep analysis of the studies that have reported on the use of advanced biomaterials and cell therapies for the regeneration of cleft lip and palate regeneration. Full article

(This article belongs to the Special Issue Biomaterials for Musculoskeletal System)

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38 pages, 1056 KiB

Open AccessReview

Platelet-Rich Fibrin Scaffolds for Cartilage and Tendon Regenerative Medicine: From Bench to Bedside

by Silvia Barbon, Elena Stocco, Veronica Macchi, Martina Contran, Francesca Grandi, Alessio Borean, Pier Paolo Parnigotto, Andrea Porzionato and Raffaele De Caro

Int. J. Mol. Sci. 2019, 20(7), 1701; https://doi.org/10.3390/ijms20071701 - 5 Apr 2019

Cited by 53 | Viewed by 6468

Abstract

Nowadays, research in Tissue Engineering and Regenerative Medicine is focusing on the identification of instructive scaffolds to address the requirements of both clinicians and patients to achieve prompt and adequate healing in case of injury. Among biomaterials, hemocomponents, and in particular Platelet-rich Fibrin [...] Read more.

Nowadays, research in Tissue Engineering and Regenerative Medicine is focusing on the identification of instructive scaffolds to address the requirements of both clinicians and patients to achieve prompt and adequate healing in case of injury. Among biomaterials, hemocomponents, and in particular Platelet-rich Fibrin matrices, have aroused widespread interest, acting as delivery platforms for growth factors, cytokines and immune/stem-like cells for immunomodulation; their autologous origin and ready availability are also noteworthy aspects, as safety- and cost-related factors and practical aspects make it possible to shorten surgical interventions. In fact, several authors have focused on the use of Platelet-rich Fibrin in cartilage and tendon tissue engineering, reporting an increasing number of in vitro, pre-clinical and clinical studies. This narrative review attempts to compare the relevant advances in the field, with particular reference being made to the regenerative role of platelet-derived growth factors, as well as the main pre-clinical and clinical research on Platelet-rich Fibrin in chondrogenesis and tenogenesis, thereby providing a basis for critical revision of the topic. Full article

(This article belongs to the Special Issue Biomaterials for Musculoskeletal System)

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20 pages, 492 KiB

Open AccessReview

Are the Biological and Biomechanical Properties of Meniscal Scaffolds Reflected in Clinical Practice? A Systematic Review of the Literature

by Chanuka D. S. Ranmuthu, Charindu K. I. Ranmuthu, Jodie C. Russell, Disha Singhania and Wasim S. Khan

Int. J. Mol. Sci. 2019, 20(3), 632; https://doi.org/10.3390/ijms20030632 - 1 Feb 2019

Cited by 11 | Viewed by 3493

Abstract

The aim of this PRISMA review was to assess whether the CMI and Actifit scaffolds, when used in clinical practice, improve clinical outcomes and demonstrate the ideal biological and biomechanical properties of scaffolds: being chondroprotective, porous, resorbable, able to mature and promote regeneration [...] Read more.

The aim of this PRISMA review was to assess whether the CMI and Actifit scaffolds, when used in clinical practice, improve clinical outcomes and demonstrate the ideal biological and biomechanical properties of scaffolds: being chondroprotective, porous, resorbable, able to mature and promote regeneration of tissue. This was done by only including studies that assessed clinical outcome and used a scale to assess both integrity of the scaffold and its effects on articular cartilage via MRI. A search was performed on PubMed, EMBASE, Scopus and clinicaltrials.gov. 2457 articles were screened, from which eight studies were selected: four used Actifit, three used CMI and one compared the two. All studies reported significant improvement in at least one clinical outcome compared to baseline. Some studies suggested that the scaffolds appeared to show porosity, mature, resorb and/or have possible chondroprotective effects, as assessed by MRI. The evidence for clinical translation is limited by differences in study methodology and small sample sizes, but is promising in terms of improving clinical outcomes in the short to mid-term. Higher level evidence, with MRI and histological evaluation of the scaffold and articular cartilage, is now needed to further determine whether these scaffolds exhibit these useful properties. Full article

(This article belongs to the Special Issue Biomaterials for Musculoskeletal System)

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17 pages, 2607 KiB

Open AccessReview

Current Trends in Fabrication of Biomaterials for Bone and Cartilage Regeneration: Materials Modifications and Biophysical Stimulations

by Agata Przekora

Int. J. Mol. Sci. 2019, 20(2), 435; https://doi.org/10.3390/ijms20020435 - 20 Jan 2019

Cited by 82 | Viewed by 7537

Abstract

The aim of engineering of biomaterials is to fabricate implantable biocompatible scaffold that would accelerate regeneration of the tissue and ideally protect the wound against biodevice-related infections, which may cause prolonged inflammation and biomaterial failure. To obtain antimicrobial and highly biocompatible scaffolds promoting [...] Read more.

The aim of engineering of biomaterials is to fabricate implantable biocompatible scaffold that would accelerate regeneration of the tissue and ideally protect the wound against biodevice-related infections, which may cause prolonged inflammation and biomaterial failure. To obtain antimicrobial and highly biocompatible scaffolds promoting cell adhesion and growth, materials scientists are still searching for novel modifications of biomaterials. This review presents current trends in the field of engineering of biomaterials concerning application of various modifications and biophysical stimulation of scaffolds to obtain implants allowing for fast regeneration process of bone and cartilage as well as providing long-lasting antimicrobial protection at the site of injury. The article describes metal ion and plasma modifications of biomaterials as well as post-surgery external stimulations of implants with ultrasound and magnetic field, providing accelerated regeneration process. Finally, the review summarizes recent findings concerning the use of piezoelectric biomaterials in regenerative medicine. Full article

(This article belongs to the Special Issue Biomaterials for Musculoskeletal System)

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22 pages, 658 KiB

Open AccessReview

Biological Properties of Calcium Phosphate Bioactive Glass Composite Bone Substitutes: Current Experimental Evidence

by Maria Karadjian, Christopher Essers, Stefanos Tsitlakidis, Bruno Reible, Arash Moghaddam, Aldo R. Boccaccini and Fabian Westhauser

Int. J. Mol. Sci. 2019, 20(2), 305; https://doi.org/10.3390/ijms20020305 - 14 Jan 2019

Cited by 72 | Viewed by 5713

Abstract

Standard treatment for bone defects is the biological reconstruction using autologous bone—a therapeutical approach that suffers from limitations such as the restricted amount of bone available for harvesting and the necessity for an additional intervention that is potentially followed by donor-site complications. Therefore, [...] Read more.

Standard treatment for bone defects is the biological reconstruction using autologous bone—a therapeutical approach that suffers from limitations such as the restricted amount of bone available for harvesting and the necessity for an additional intervention that is potentially followed by donor-site complications. Therefore, synthetic bone substitutes have been developed in order to reduce or even replace the usage of autologous bone as grafting material. This structured review focuses on the question whether calcium phosphates (CaPs) and bioactive glasses (BGs), both established bone substitute materials, show improved properties when combined in CaP/BG composites. It therefore summarizes the most recent experimental data in order to provide a better understanding of the biological properties in general and the osteogenic properties in particular of CaP/BG composite bone substitute materials. As a result, BGs seem to be beneficial for the osteogenic differentiation of precursor cell populations in-vitro when added to CaPs. Furthermore, the presence of BG supports integration of CaP/BG composites into bone in-vivo and enhances bone formation under certain circumstances. Full article

(This article belongs to the Special Issue Biomaterials for Musculoskeletal System)

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13 pages, 3961 KiB

Open AccessTechnical Note

Innovative Strategy for 3D Transfection of Primary Human Stem Cells with BMP-2 Expressing Plasmid DNA: A Clinically Translatable Strategy for Ex Vivo Gene Therapy

by Maruthibabu Paidikondala, Sandeep Kadekar and Oommen P. Varghese

Int. J. Mol. Sci. 2019, 20(1), 56; https://doi.org/10.3390/ijms20010056 - 23 Dec 2018

Cited by 13 | Viewed by 10413

Abstract

Ex vivo gene therapy offers enormous potential for cell-based therapies, however, cumbersome in vitro cell culture conditions have limited its use in clinical practice. We have optimized an innovative strategy for the transient transfection of bone morphogenetic protein-2 (BMP-2) expressing plasmids in suspended [...] Read more.

Ex vivo gene therapy offers enormous potential for cell-based therapies, however, cumbersome in vitro cell culture conditions have limited its use in clinical practice. We have optimized an innovative strategy for the transient transfection of bone morphogenetic protein-2 (BMP-2) expressing plasmids in suspended human stem cells within 5-min that enables efficient loading of the transfected cells into a 3D hydrogel system. Such a short incubation time for lipid-based DNA nanoparticles (lipoplexes) reduces cytotoxicity and at the same time reduces the processing time for cells to be transplanted. The encapsulated human mesenchymal stromal/stem cells (hMSCs) transfected with BMP-2 plasmid demonstrated high expression of an osteogenic transcription factor, namely RUNX2, but not the chondrogenic factor (SOX9), within the first three days. This activation was also reflected in the 7-day and 21-day experiment, which clearly indicated the induction of osteogenesis but not chondrogenesis. We believe our transient transfection method demonstrated in primary MSCs can be adapted for other therapeutic genes for different cell-based therapeutic applications. Full article

(This article belongs to the Special Issue Biomaterials for Musculoskeletal System)

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