Research

16 pages, 4022 KiB

Open AccessArticle

Mesenchymal Stem Cells Coated with Synthetic Bone-Targeting Polymers Enhance Osteoporotic Bone Fracture Regeneration

by Yuliya Safarova (Yantsen), Farkhad Olzhayev, Bauyrzhan Umbayev, Andrey Tsoy, Gonzalo Hortelano, Tursonjan Tokay, Hironobu Murata, Alan Russell and Sholpan Askarova

Bioengineering 2020, 7(4), 125; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering7040125 - 12 Oct 2020

Cited by 1 | Viewed by 3555

Abstract

Osteoporosis is a progressive skeletal disease characterized by reduced bone density leading to bone fragility and an elevated risk of bone fractures. In osteoporotic conditions, decrease in bone density happens due to the augmented osteoclastic activity and the reduced number of osteoblast progenitor [...] Read more.

Osteoporosis is a progressive skeletal disease characterized by reduced bone density leading to bone fragility and an elevated risk of bone fractures. In osteoporotic conditions, decrease in bone density happens due to the augmented osteoclastic activity and the reduced number of osteoblast progenitor cells (mesenchymal stem cells, MSCs). We investigated a new method of cell therapy with membrane-engineered MSCs to restore the osteoblast progenitor pool and to inhibit osteoclastic activity in the fractured osteoporotic bones. The primary active sites of the polymer are the N-hydroxysuccinimide and bisphosphonate groups that allow the polymer to covalently bind to the MSCs’ plasma membrane, target hydroxyapatite molecules on the bone surface and inhibit osteolysis. The therapeutic utility of the membrane-engineered MSCs was investigated in female rats with induced estrogen-dependent osteoporosis and ulnar fractures. The analysis of the bone density dynamics showed a 27.4% and 21.5% increase in bone density at 4 and 24 weeks after the osteotomy of the ulna in animals that received four transplantations of polymer-modified MSCs. The results of the intravital observations were confirmed by the post-mortem analysis of histological slices of the fracture zones. Therefore, this combined approach that involves polymer and cell transplantation shows promise and warrants further bio-safety and clinical exploration. Full article

(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering)

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19 pages, 5665 KiB

Open AccessArticle

Mechanical Enhancement of Cytocompatible 3D Scaffolds, Consisting of Hydroxyapatite Nanocrystals and Natural Biomolecules, Through Physical Cross-Linking

by Despoina Brasinika, Elias P. Koumoulos, Kyriaki Kyriakidou, Eleni Gkartzou, Maria Kritikou, Ioannis K. Karoussis and Costas A. Charitidis

Bioengineering 2020, 7(3), 96; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering7030096 - 19 Aug 2020

Cited by 3 | Viewed by 3723

Abstract

Bioinspired scaffolds mimicking natural bone-tissue properties holds great promise in tissue engineering applications towards bone regeneration. Within this work, a way to reinforce mechanical behavior of bioinspired bone scaffolds was examined by applying a physical crosslinking method. Scaffolds consisted of hydroxyapatite nanocrystals, biomimetically [...] Read more.

Bioinspired scaffolds mimicking natural bone-tissue properties holds great promise in tissue engineering applications towards bone regeneration. Within this work, a way to reinforce mechanical behavior of bioinspired bone scaffolds was examined by applying a physical crosslinking method. Scaffolds consisted of hydroxyapatite nanocrystals, biomimetically synthesized in the presence of collagen and l-arginine. Scaffolds were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), microcomputed tomography, and nanoindentation. Results revealed scaffolds with bone-like nanostructure and composition, thus an inherent enhanced cytocompatibility. Evaluation of porosity proved the development of interconnected porous network with bimodal pore size distribution. Mechanical reinforcement was achieved through physical crosslinking with riboflavin irradiation, and nanoindentation tests indicated that within the experimental conditions of 45% humidity and 37 °C, photo-crosslinking led to an increase in the scaffold’s mechanical properties. Elastic modulus and hardness were augmented, and specifically elastic modulus values were doubled, approaching equivalent values of trabecular bone. Cytocompatibility of the scaffolds was assessed using MG63 human osteosarcoma cells. Cell viability was evaluated by double staining and MTT assay, while attachment and morphology were investigated by SEM. The results suggested that scaffolds provided a cell friendly environment with high levels of viability, thus supporting cell attachment, spreading and proliferation. Full article

(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering)

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21 pages, 3576 KiB

Open AccessArticle

Material-Dependent Formation and Degradation of Bone Matrix—Comparison of Two Cryogels

by Weidong Weng, Victor Häussling, Romina H. Aspera-Werz, Fabian Springer, Helen Rinderknecht, Bianca Braun, Markus A. Küper, Andreas K. Nussler and Sabrina Ehnert

Bioengineering 2020, 7(2), 52; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering7020052 - 05 Jun 2020

Cited by 7 | Viewed by 4296

Abstract

Cryogels represent ideal carriers for bone tissue engineering. We recently described the osteogenic potential of cryogels with different protein additives, e.g., platelet-rich plasma (PRP). However, these scaffolds raised concerns as different toxic substances are required for their preparation. Therefore, we developed another gelatin [...] Read more.

Cryogels represent ideal carriers for bone tissue engineering. We recently described the osteogenic potential of cryogels with different protein additives, e.g., platelet-rich plasma (PRP). However, these scaffolds raised concerns as different toxic substances are required for their preparation. Therefore, we developed another gelatin (GEL)-based cryogel. This study aimed to compare the two scaffolds regarding their physical characteristics and their influence on osteogenic and osteoclastic cells. Compared to the PRP scaffolds, GEL scaffolds had both larger pores and thicker walls, resulting in a lower connective density. PRP scaffolds, with crystalized calcium phosphates on the surface, were significantly stiffer but less mineralized than GEL scaffolds with hydroxyapatite incorporated within the matrix. The GEL scaffolds favored adherence and proliferation of the osteogenic SCP-1 and SaOS-2 cells. Macrophage colony-stimulating factor (M-CSF) and osteoprotegerin (OPG) levels seemed to be induced by GEL scaffolds. Levels of other osteoblast and osteoclast markers were comparable between the two scaffolds. After 14 days, mineral content and stiffness of the cryogels were increased by SCP-1 and SaOS-2 cells, especially of PRP scaffolds. THP-1 cell-derived osteoclastic cells only reduced mineral content and stiffness of PRP cryogels. In summary, both scaffolds present powerful advantages; however, the possibility to altered mineral content and stiffness may be decisive when it comes to using PRP or GEL scaffolds for bone tissue engineering. Full article

(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering)

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10 pages, 4195 KiB

Open AccessArticle

Copper-Doped Ordered Mesoporous Bioactive Glass: A Promising Multifunctional Platform for Bone Tissue Engineering

by Francesco Baino

Bioengineering 2020, 7(2), 45; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering7020045 - 21 May 2020

Cited by 31 | Viewed by 5199

Abstract

The design and development of biomaterials with multifunctional properties is highly attractive in the context of bone tissue engineering due to the potential of providing multiple therapies and, thus, better treatment of diseases. In order to tackle this challenge, copper-doped silicate mesoporous bioactive [...] Read more.

The design and development of biomaterials with multifunctional properties is highly attractive in the context of bone tissue engineering due to the potential of providing multiple therapies and, thus, better treatment of diseases. In order to tackle this challenge, copper-doped silicate mesoporous bioactive glasses (MBGs) were synthesized via a sol-gel route coupled with an evaporation-induced self-assembly process by using a non-ionic block co-polymer as a structure directing agent. The structure and textural properties of calcined materials were investigated by X-ray powder diffraction, scanning-transmission electron microscopy and nitrogen adsorption-desorption measurements. In vitro bioactivity was assessed by immersion tests in simulated body fluid (SBF). Preliminary antibacterial tests using Staphylococcus aureus were also carried out. Copper-doped glasses revealed an ordered arrangement of mesopores (diameter around 5 nm) and exhibited apatite-forming ability in SBF along with promising antibacterial properties. These results suggest the potential suitability of copper-doped MBG powder for use as a multifunctional biomaterial to promote bone regeneration (bioactivity) and prevent/combat microbial infection at the implantation site, thereby promoting tissue healing. Full article

(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering)

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17 pages, 6080 KiB

Open AccessArticle

Strontium- and Zinc-Containing Bioactive Glass and Alginates Scaffolds

by Asfia Haider, Ahmad Waseem, Natalia Karpukhina and Sahar Mohsin

Bioengineering 2020, 7(1), 10; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering7010010 - 13 Jan 2020

Cited by 23 | Viewed by 6501

Abstract

With an increasingly elderly population, there is a proportionate increase in bone injuries requiring hospitalization. Clinicians are increasingly adopting tissue-engineering methods for treatment due to limitations in the use of autogenous and autologous grafts. The aim of this study was to synthesize a [...] Read more.

With an increasingly elderly population, there is a proportionate increase in bone injuries requiring hospitalization. Clinicians are increasingly adopting tissue-engineering methods for treatment due to limitations in the use of autogenous and autologous grafts. The aim of this study was to synthesize a novel, bioactive, porous, mechanically stable bone graft substitute/scaffold. Strontium- and zinc-containing bioactive glasses were synthesized and used with varying amounts of alginate to form scaffolds. Differential scanning calorimetric analysis (DSC), FTIR, XRD, and NMR techniques were used for the characterization of scaffolds. SEM confirmed the adequate porous structure of the scaffolds required for osteoconductivity. The incorporation of the bioactive glass with alginate has improved the compressive strength of the scaffolds. The bioactivity of the scaffolds was demonstrated by an increase in the pH of the medium after the immersion of the scaffolds in a Tris/HCl buffer and by the formation of orthophosphate precipitate on scaffolds. The scaffolds were able to release calcium, strontium and zinc ions in the Tris/HCl buffer, which would have a positive impact on osteogenesis if tested in vivo. Full article

(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering)

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Review

Jump to: Research, Other

10 pages, 568 KiB

Open AccessReview

Computational Challenges in Tissue Engineering for the Spine

by André P. G. Castro

Bioengineering 2021, 8(2), 25; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering8020025 - 15 Feb 2021

Cited by 6 | Viewed by 3441

Abstract

This paper deals with a brief review of the recent developments in computational modelling applied to innovative treatments of spine diseases. Additionally, it provides a perspective on the research directions expected for the forthcoming years. The spine is composed of distinct and complex [...] Read more.

This paper deals with a brief review of the recent developments in computational modelling applied to innovative treatments of spine diseases. Additionally, it provides a perspective on the research directions expected for the forthcoming years. The spine is composed of distinct and complex tissues that require specific modelling approaches. With the advent of additive manufacturing and increasing computational power, patient-specific treatments have moved from being a research trend to a reality in clinical practice, but there are many issues to be addressed before such approaches become universal. Here, it is identified that the major setback resides in validation of these computational techniques prior to approval by regulatory agencies. Nevertheless, there are very promising indicators in terms of optimised scaffold modelling for both disc arthroplasty and vertebroplasty, powered by a decisive contribution from imaging methods. Full article

(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering)

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24 pages, 3849 KiB

Open AccessReview

Mineralization of Biomaterials for Bone Tissue Engineering

by Xinchen Wu, Kierra Walsh, Brianna L. Hoff and Gulden Camci-Unal

Bioengineering 2020, 7(4), 132; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering7040132 - 20 Oct 2020

Cited by 43 | Viewed by 9728

Abstract

Mineralized biomaterials have been demonstrated to enhance bone regeneration compared to their non-mineralized analogs. As non-mineralized scaffolds do not perform as well as mineralized scaffolds in terms of their mechanical and surface properties, osteoconductivity and osteoinductivity, mineralization strategies are promising methods in the [...] Read more.

Mineralized biomaterials have been demonstrated to enhance bone regeneration compared to their non-mineralized analogs. As non-mineralized scaffolds do not perform as well as mineralized scaffolds in terms of their mechanical and surface properties, osteoconductivity and osteoinductivity, mineralization strategies are promising methods in the development of functional biomimetic bone scaffolds. In particular, the mineralization of three-dimensional (3D) scaffolds has become a promising approach for guided bone regeneration. In this paper, we review the major approaches used for mineralizing tissue engineering constructs. The resulting scaffolds provide minerals chemically similar to the inorganic component of natural bone, carbonated apatite, Ca₅(PO₄,CO₃)₃(OH). In addition, we discuss the characterization techniques that are used to characterize the mineralized scaffolds, such as the degree of mineralization, surface characteristics, mechanical properties of the scaffolds, and the chemical composition of the deposited minerals. In vitro cell culture studies show that the mineralized scaffolds are highly osteoinductive. We also summarize, based on literature examples, the applications of 3D mineralized constructs, as well as the rationale behind their use. The mineralized scaffolds have improved bone regeneration in animal models due to the enhanced mechanical properties and cell recruitment capability making them a preferable option for bone tissue engineering over non-mineralized scaffolds. Full article

(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering)

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33 pages, 1207 KiB

Open AccessReview

Implementation of Endogenous and Exogenous Mesenchymal Progenitor Cells for Skeletal Tissue Regeneration and Repair

by Salomi Desai and Chathuraka T. Jayasuriya

Bioengineering 2020, 7(3), 86; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering7030086 - 04 Aug 2020

Cited by 9 | Viewed by 5312

Abstract

Harnessing adult mesenchymal stem/progenitor cells to stimulate skeletal tissue repair is a strategy that is being actively investigated. While scientists continue to develop creative and thoughtful ways to utilize these cells for tissue repair, the vast majority of these methodologies can ultimately be [...] Read more.

Harnessing adult mesenchymal stem/progenitor cells to stimulate skeletal tissue repair is a strategy that is being actively investigated. While scientists continue to develop creative and thoughtful ways to utilize these cells for tissue repair, the vast majority of these methodologies can ultimately be categorized into two main approaches: (1) Facilitating the recruitment of endogenous host cells to the injury site; and (2) physically administering into the injury site cells themselves, exogenously, either by autologous or allogeneic implantation. The aim of this paper is to comprehensively review recent key literature on the use of these two approaches in stimulating healing and repair of different skeletal tissues. As expected, each of the two strategies have their own advantages and limitations (which we describe), especially when considering the diverse microenvironments of different skeletal tissues like bone, tendon/ligament, and cartilage/fibrocartilage. This paper also discusses stem/progenitor cells commonly used for repairing different skeletal tissues, and it lists ongoing clinical trials that have risen from the implementation of these cells and strategies. Lastly, we discuss our own thoughts on where the field is headed in the near future. Full article

(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering)

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Other

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11 pages, 2403 KiB

Open AccessPerspective

Cell Scaffolds for Bone Tissue Engineering

by Kazutoshi Iijima and Hidenori Otsuka

Bioengineering 2020, 7(4), 119; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering7040119 - 30 Sep 2020

Cited by 17 | Viewed by 3783

Abstract

Currently, well-known surgical procedures for bone defects are classified into four types: (1) autogenous bone graft transplantation, (2) allogeneic bone graft transplantation, (3) xenogeneic bone graft transplantation, and (4) artificial bone graft transplantation. However, they are often risky procedures and related to postoperative [...] Read more.

Currently, well-known surgical procedures for bone defects are classified into four types: (1) autogenous bone graft transplantation, (2) allogeneic bone graft transplantation, (3) xenogeneic bone graft transplantation, and (4) artificial bone graft transplantation. However, they are often risky procedures and related to postoperative complications. As an alternative, tissue engineering to regenerate new bone often involves the use of mesenchymal stem cells (MSCs), derived from bone marrow, adipose tissues, and so on, which are cultured into three-dimensional (3D) scaffolds to regenerate bone tissue by osteoinductive signaling. In this manuscript, we provide an overview of recent treatment of bone defects and the studies on the creation of cell scaffolds for bone regeneration. Bone regeneration from bone marrow-derived mesenchymal stem cells using silica nonwoven fabric by the authors’ group were provided. Potential application and future direction of the present systems were also described. Full article

(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering)

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