Fig 11 - uploaded by Håvard J Haugen
Content may be subject to copyright.
(A) A schematic of poly(ether ether ketone) (PEEK) surface phosphorylation. (B) Scanning electron microscopy (SEM) images of the biomaterial surface. S-NT: unmodified PEEK, S-PT: phosphorylated PEEK with a smooth surface, R-NT: sandblasted PEEK, R-PT: phosphorylated PEEK with a sandblasted surface. (C) Biomaterial implantation in the rabbit tibia. Illustrative histological images of neo-tissue formation and osseointegration of samples four weeks after surgery. The white arrows show neo-tissue formation at the interface with substrates. Scale bars, 500 mm. Reprinted from ref. 220. Copyright r 2018, Springer Nature in accordance to Creative Commons Attribution License.
Source publication
Biomedical scientists use chemistry-driven processes found in nature as an inspiration to design biomaterials as promising diagnostic tools, therapeutic solutions, or tissue substitutes. While substantial consideration is devoted to the design and validation of biomaterials, the nature of their interactions with the surrounding biological microenvi...
Contexts in source publication
Context 1
... (Fig. 11A). Fig. 11B shows that phosphorylation of the surface enhances cell responses on both smooth and rough surfaces, with more improvement on rough surfaces. However, only modifying the surface roughness cannot improve MSC responses. Fig. 11C shows the substantial effects of the combined surface modification strategies on bone regeneration ...
Context 2
... (Fig. 11A). Fig. 11B shows that phosphorylation of the surface enhances cell responses on both smooth and rough surfaces, with more improvement on rough surfaces. However, only modifying the surface roughness cannot improve MSC responses. Fig. 11C shows the substantial effects of the combined surface modification strategies on bone regeneration in the ...
Context 3
... (Fig. 11A). Fig. 11B shows that phosphorylation of the surface enhances cell responses on both smooth and rough surfaces, with more improvement on rough surfaces. However, only modifying the surface roughness cannot improve MSC responses. Fig. 11C shows the substantial effects of the combined surface modification strategies on bone regeneration in the rabbit tibia. 220 Both chemistry and roughness properties of the surface play roles in neo-tissue ...
Context 4
... 218 The same roughness value in two different types of materials can affect cell responses differently, which can be owing to the differences in their chemistry. [219][220][221][222] Fukuda et al. 220 investigated the osseointegration ability of a poly(ether ether ketone) implant by enhancing its surface roughness and/or surface chemistry (Fig. 11A). Fig. 11B shows that phosphorylation of the surface enhances cell responses on both smooth and rough surfaces, with more improvement on rough surfaces. However, only modifying the surface roughness cannot improve MSC responses. Fig. 11C shows the substantial effects of the combined surface modification strategies on bone regeneration ...
Context 5
... The same roughness value in two different types of materials can affect cell responses differently, which can be owing to the differences in their chemistry. [219][220][221][222] Fukuda et al. 220 investigated the osseointegration ability of a poly(ether ether ketone) implant by enhancing its surface roughness and/or surface chemistry (Fig. 11A). Fig. 11B shows that phosphorylation of the surface enhances cell responses on both smooth and rough surfaces, with more improvement on rough surfaces. However, only modifying the surface roughness cannot improve MSC responses. Fig. 11C shows the substantial effects of the combined surface modification strategies on bone regeneration in the ...
Context 6
... ability of a poly(ether ether ketone) implant by enhancing its surface roughness and/or surface chemistry (Fig. 11A). Fig. 11B shows that phosphorylation of the surface enhances cell responses on both smooth and rough surfaces, with more improvement on rough surfaces. However, only modifying the surface roughness cannot improve MSC responses. Fig. 11C shows the substantial effects of the combined surface modification strategies on bone regeneration in the rabbit tibia. 220 Both chemistry and roughness properties of the surface play roles in neo-tissue ...
Citations
... Instead, it can adhere to the protein layer adsorbed on the material surface [62]. Cell adhesion can be studied using the spatial organization of arginine-glycineaspartic acid (RGD) ligands [64]- [66]. In a previous study, Cavalcanti-Adam et al. [67] produced a threshold density (70 nm) for the RGD spacing for the focal adhesion to be formed. ...
Since the initial presentation of cell contact response with native topographic structure in 1911, numerous studies have been published to investigate how cells respond when interacting with micro/nano structures.. Many of the founding has potential to become applications in bio-medical or in pharmaceutical industry. Regardless of the huge prospect, these applications are still bound to the manufacturability of the micro/nano topographic structures. The introduction of nanoimprint lithography in 1995 has demonstrated that it can replicating micro/nano structures with relatively simple and low-cost equipment but with high throughput and high reliability. This paper reviews the development in cell-micro/nanotopographic interactions, the development of high throughput nanofabrication method. The nanofabrication methods in focus is nanoimprint lithography and electrospinning. This review paper also discusses the potential applications from cell-nanotopographic for mass productions. Prospectus applications such as the development in development of antimicrobial surfaces interactions and biologically inspired nanoscaffold and nanopattern suitable for tissue repair and regeneration are also discussed.
... Macrophages, intrinsic immune cells, play pivotal roles in foreign body reactions and wound healing following biomaterial implantation. In foreign body reactions, macrophages can polarize into distinct phenotypes, primarily M1 (pro-inflammatory) and M2 (anti-inflammatory) [37]. These two macrophage phenotypes distinctly influence tissue repair. ...
The ideal tissue engineering scaffold should facilitate rapid cell infiltration and provide an optimal immune microenvironment during interactions with the host. Electrospinning can produce two-dimensional (2D) membranes mimicking the extracellular matrix. However, their dense structure hinders cell penetration, and their thin form restricts scaffold utility. In this study, latticed hydrogels were three-dimensional (3D) printed onto electrospun membranes. This technique allowed for layer-by-layer assembly of the membranes into 3D scaffolds, which maintained their resilience impressively under both dry and wet conditions. We assessed the cellular and host responses of these 3D nanofiber scaffolds by comparing random membranes and mesh-like membranes with three different mesh sizes (250, 500, and 750 μm). It was found that scaffolds with a mesh size of 500 μm were superior for M2 macrophage phenotype polarization, vascularization, and matrix deposition. Furthermore, it was confirmed by subsequent experiments such as RNA sequencing that the mesh-like topology may promote polarization to the M2 phenotype by affecting the PI3K/AKT pathway. In conclusion, our work offers a novel method for transforming 2D nanofiber membranes into 3D scaffolds. This method boasts flexibility, allowing for the use of varied electrospun membranes and hydrogels in terms of structure and composition. It has vast potential in tissue repair and regeneration.
... Salt lakes are the most critical ecosystems on earth and are found worldwide. These lakes are significant in determining the region's climate and biodiversity, keeping ecological health, recreational services, and other resources (Chen et al., 2021;Lee, 2018;Rahmati et al., 2020;Arami et al., 2018). With careful assessments of environmental factors, i.e., all human activities such as lake water diversion, salinization, mining, pollution, and weather change, saline lakes are threatened at different times (Heydari et al., 2012;Khazaei et al., 2019). ...
Environmental crises in Iran, including lack of rainfall and drying rivers, wetlands, and lakes, have caused natural and human hazards and vulnerabilities. Meanwhile, the drying of Urmia Lake as a national crisis can significantly create natural and human problems and risks. In this paper, based on annual Landsat satellite images and long-term changes in land cover using the output of the GEE system, we investigate shifts in the water level of Lake Urmia. The effects of its drying on the trend of population changes in surrounding settlements (cities and villages) from 1986 to 2021 indicate that Urmia Lake’s water level is expected to be 1271.39 m in 2021. The lake’s salt area has increased by 465 Km2 due to its drying trend from 1986 to 2021. The water level estimate for the lake in November 1986 was 1275 m, indicating a 3.7-meter drop in Urmia Lake’s water level. Indeed, from 1995 to 2021, the lake lost approximately 48% of its area and 89% of its volume. It was observed that water reduction has a negative effect on the level of Urmia Lake. Modis imagery -using the Linear Fit algorithm- shows an unbalanced relationship in lake water use between 1986 and 2021. The trend of the water area decreasing in Urmia Lake caused five centers of salt dust in the lake. The dust from the five centers significantly impacted the surrounding settlements (cities and villages). Most of the towns in a county like Tabriz (-3.3%), Azarshahr (-0.7%), and Malekan (-0.6%) have negative population growth instead, in urban areas like Urmia (4.3%), Osku (7%), and Azarshahr (3.4%). Increasing in the population happened. Thus, drying lakes and dust and salt centers have a terrible effect on more than 7 million people in villages and cities and intensified migration from 1986 to 2021.
... It could be found that all scaffolds had a regular 3D porous structure, which facilitates the growth of osteoblasts and blood vessels (Swanson et al., 2021). In particular, when the BMP-2/PLGA microspheres were compounded with PC scaffolds, the scaffold surface became rougher, which was more favorable to the adhesion of osteoblasts (Chen et al., 2018;Rahmati et al., 2020). ...
Treatment of large and complex irregular bone defects is a major clinical challenge in orthopedic surgery. The current treatment includes bone transportation using the Ilizarov technique and bone cement repair using the Masquelet technique, but they require long-term manual intervention or secondary operation. To improve this situation, we compared the different implanting materials in the literature published in the past 10 years, finding that glycolic acid copolymer (PLGA) and Calcium sulfate (CaSO 4 ) are appropriated to be used as synthetic bone materials due to their advantages of easy-availability, nontoxicity, osteogenic properties and rapid degradation. Meanwhile, the development of 3D printing technique and devices makes it relatively easier to synthetize customized bio-mimetic porous scaffolds, thus facilitating the release of modified protein. In this study, we compounded BMP-2/PLGA microspheres with polylactic glycolic acid copolymer/CaSO 4 (PC) 3D printed scaffold to improve the osteogenic properties of the scaffold. The result of our in vitro experiment demonstrated that the prepared PCB scaffold not only had satisfactory bio-compatibility, but also promoted osteogenic differentiation. This 3D printed scaffold is capable to accelerate the repair of complex bone defects by promoting new bone formation, suggesting that it may prove to be a potential bone tissue engineering substitute.
... Hollinger et al., 1996; Kurtza and Devine, 2007; Lee and Mooney, 2002;Rahmati et al.母床骨)から新たに骨組織を呼び込む骨伝導性という性質を持つ(LeGeros, 2002)。こ A d v a n c e P u b l i c a t i He et al., 2019; Ishikawa, 2019; Putri et al., 2020; Sugiura et al., 2018)alkaline phosphatase: ALP) ，タイプ I コラーゲン，オステオポンチン (osteopontin: OPN) ，オステオカルシン(osteocalcin: OCN) )などの産生量を大きく向上さ せることが知られている(Ming et al., 2004; Obata et al., 2009; Reffitt et al., 2003;Su et al., 2014;Wang et al., 2014;Xynos et al., 2000)。このように，シリカは担持材として非常に有望である一方で，シリカ源として用いられる，テトラエチルオルトシリケート(tetraethyl orthosilicate: TEOS)をはじめとする有機シリカ起源の残存有機分子の為害性リスクから，骨補填材への 添加がためらわれてきた経緯がある。 我々は，これまでイオン挿入法と名付けた独自の技術を駆使し，リン酸カルシウム，特に 幼若骨の主要無機成分であるリン酸八カルシウム (octacalcium phosphate: OCP) 結晶への様々 なイオン・分子担持法を提案してきた(Sugiura, 2022; Sugiura and Makita, 2018; Sugiura and Makita, 2019a; Sugiura et al., 2019b; Sugiura et al., 2019a; Sugiura et al., 2022a)。OCP 結晶中に， 置換の形でジカルボン酸分子を担持可能であることはよく知られている(Markovic et al., 1993; Sugiura and Makita, 2019b; Tsai et al., 2010)。しかし，我々は本メカニズムを深く検討し A d v a n c e P u b l i c a t i o n ていくことにより，ジカルボン酸分子以外のイオン・分子についても，骨補填材としての要 望を満足させつつ担持させることを試みた。 シリカについて，有機シリカを用いずに，無機的に担持させる手法について検討を進めた。 酸性-弱塩基環境下においては，シリカは溶解せず，強塩基性においては Na2SiO3 などの組 成で溶解する(Marshall, 1980)。水ガラスの通称で知られている Na2SiO3 溶液は，強塩基性を 呈するため，これまでよく知られている OCP の形成環境である弱酸性-弱塩基性環境とは 一見乖離しているようにも見える。その一方で，OCP の形成を誘導する Na イオンを豊富に 含んでいる(Sugiura and Makita, 2018; Sugiura et al., 2019a; Sugiura and Makita, 2019c; Sugiura et al., 2021a)。驚くべきことに，適切な濃度に希釈した Na2SiO3 溶液中で，市販の易溶性リン酸 カルシウムであるリン酸水素カルシウム二水和物を加水分解させるだけで，OCP を得るこ とが出来た(Fig. 3) 。エネルギー分散型検出器付き走査透過電子顕微鏡(high-angle annular dark-field scanning transmission electron microscopy with energy dispersive X-ray spectroscopy: STEM-HAADF/EDX)にて観察すると，Si が元素レベルで Ca，P と均一に分布している様子 が観察される。 また， 高分解能透過電子顕微鏡 (high-resolution transmission electron microscopy: HR-TEM)観察では，明瞭な格子像が得られた(Sugiura et al., 2021b)。得られた OCP を，赤 外分光分析や，核磁気共鳴分光法(nuclear magnetic resonance: NMR)など，分光学的に詳細 に解析すると，OCP 中の含水層と呼称される，ジカルボン酸分子などが置換可能な部位に シリカがリン酸イオンと置換する形で担持されていることが分かった (Fig. 4) 。 これにより， A d v a n c e P u b l i c a t i Sugiura et al., 2022b; Sugiura et al., 2023a; Sugiura et al., 2023b)。尚，本検討の詳細については，原著をあたられたい(Sugiura et al. に示すように， Na2SiO3 溶液を適切な濃度 (17~22 wt%) として混合泥を調製すると， A d v a n c e P u b l i c a t i o n OCP 単相からなるブロック体を調製することが出来た (Sugiura et al., 2023c)。本ブロック体 の機械的強度について，圧縮強度試験を行ったところ，約 3MPa と，骨補填材として埋入可 能な強度を保持していることが分かった。 また， NMR などの解析により， シリカ分子が OCP for biomaterial. ...
In orthopedics and oral surgery, clinical trials are being conducted to examine the reconstruction and regeneration of bone defects caused by injuries and diseases. Bone substitutes, mainly composed of calcium phosphate, are employed as biomaterials to reconstruct and regenerate bone defects that cannot be covered by autogenous bone grafts. However, the bone regeneration abilities of existing bone grafting materials are insufficient. Most candidates for bone grafting materials are elderly patients older than 60 years, so improving the bone regeneration capacity of bone grafting materials is a major clinical problem. We have been investigating the enhancement of bone substitutes via ionic insertion, an original method of controlling calcium phosphate crystals and adding elements. In this review, we describe our studies on the addition of silica, a bone-active factor, to calcium phosphate and the usefulness of silica-loaded calcium phosphate as a bone replacement material based on the ionic insertion method. The bone regeneration ability of silica-loaded calcium phosphate was several times higher than that of the current carbonate apatite bone material. Silica-loaded calcium phosphate is expected to be applicable to clinical cases that were difficult to apply in the past; it will also significantly help improve the quality of life of patients, especially the elderly.
... However, synthetic biomaterials also present some limitations such as a lack of osteoconductivity or high resorption rates that might compromise the volumetric dimensions of the regenerated bone [28,29]. Given all this, producing optimized synthetic CaP biomaterials is crucially dependent on the fundamental understanding of the influence of the physicochemical biomaterial properties on the bone healing mechanisms [30] ( Fig. 1). ...
... Hence, the in vitro results suggest an exceptionally good cytocompatibility for the hyaluronic acid gels crosslinked with BDDE and PEGDE. However, a single cell, 2D environment is not able to replicate the complexity of human physiology; it is therefore recommended to conduct a thorough in vivo investigation to understand the biomaterial's biological performance precisely [44]. ...
Hyaluronic acid (HA) is a versatile biomaterial frequently utilized in regenerative medicine due to its gel-like properties, making it well-suited for clinical applications. However, its linear form is susceptible to rapid enzymatic degradation, limiting its longevity within the body. To address this challenge, extensive research has focused on crosslinking mechanisms to enhance the durability of HA gels. One early approach involved cross-linking HA with 1,4-butanediol diglycidyl ether (BDDE) to create HA-BDDE, a clinically used product since the 1990s. However, the manufacturing process for HA-BDDE, primarily used in industry, lacks comprehensive documentation in the literature. More recently, poly(propylene glycol) diglycidyl ether (PEGDE) has emerged as an alternative to BDDE for crosslinking, offering improved gel elasticity and reduced cytotoxicity. In this study, we present the manufacturing process for producing both crosslinked gels, HA-BDDE and HA-PEGDE, with negligible residual crosslinkers, as confirmed by FTIR and NMR analysis. We characterize the crosslinking ki-netics and the resulting formulations, revealing that HA-PEGDE gel exhibits comparable stiffness (G' = 60 Pa vs. 75 Pa) to HA-BDDE, despite a lower effective crosslinking ratio (CrR = 0.12 vs. 0.24). Intriguingly, our cyto-toxicity testing demonstrates significantly greater cell viability for HA-PEGDE compared to HA-BDDE (151% versus 105%). Overall, both gels can be readily manufactured using a similar process and demonstrate excellent in vitro biocompatibility. This study elucidates why HA-BDDE is widely utilized in clinical settings and underscores the potential promise of HA-PEGDE as an emerging variant for clinical applications.
... Over the past decades, materials and their interface designs for excellent cell response have attracted extensive attention for their potential application in many fields with respect to tissue engineering and cellular therapies [1][2][3][4]. The interface of materials, which is responsible for the initial interactions between a cell and a foreign substrate, plays a crucial role in determining cell response to materials, including aspects such as compatibility, cell adhesion, proliferation, and subsequent cell fate [5,6]. ...
The improvement of the capability of poly(N-isopropylacrylamide) (PNIPAAm) hydrogel coating in cell adhesion and detachment is critical to efficiently prepare cell sheets applied in cellular therapies and tissue engineering. To enhance cell response on the surface, the amine group-modified PNIPAAm (PNIPAAm-APTES) nanohydrogels were synthesized and deposited spontaneously on tannic acid (TA)-modified polyethylene (PE) plates. Subsequently, TA was introduced onto PNIPAAm-APTES nanohydrogels to fabricate coatings composed of TA-modified PNIPAAm-APTES (PNIPAAm-APTES-TA). Characterization techniques, including TEM, SEM, XPS, and UV-Vis spectroscopy, confirmed the effective deposition of hydrogels of PNIPAAm as well as the morphologies, content of chemical bonding-TA, and stability of various coatings. Importantly, the porous hydrogel coatings exhibited superhydrophilicity at 20 °C and thermo-responsive behavior. The fluorescence measurement demonstrated that the coating’s stability effectively regulated protein behavior, influencing cell response. Notably, cell response tests revealed that even without precise control over the chain length/thickness of PNIPAAm during synthesis, the coatings enhanced cell adhesion and detachment, facilitating efficient cell culture. This work represented a novel and facile approach to preparing bioactive PNIPAAm for cell culture.
... An imbalance between osteoblasts and osteoclasts disrupts the bone structure and affects the stability of the implant [5], which eventually leads to implant loss [6]. Studies have shown that most postimplant failures derive from the suppression of osteoblast function and overactivity of osteoclasts on the implant surface [7]. Therefore, dedicate control of the ratio between bone formation and resorption, ensuring a constant bone volume and maintaining bone homeostasis [8], via optimization of the biological properties of the implant is highly desirable [9]. ...
The ideal implant surface plays a substantial role in maintaining bone homeostasis by simultaneously promoting osteoblast differentiation and limiting overactive osteoclast activity to a certain extent, which leads to satisfactory dynamic osseointegration. However, the rational search for implant materials with an ideal surface structure is challenging and a hot research topic in the field of tissue engineering. In this study, we constructed titanium dioxide titanium nanotubes (TNTs) by anodic oxidation and found that this structure significantly promoted osteoblast differentiation and inhibited osteoclast formation and function while simultaneously inhibiting the total protein levels of proline-rich tyrosine kinase 2 (PYK2) and focal adhesion kinase (FAK). Knockdown of the PYK2 gene by siRNA significantly suppressed the number and osteoclastic differentiation activity of mouse bone marrow mononuclear cells (BMMs), while overexpression of PYK2 inhibited osteogenesis and increased osteoclastic activity. Surprisingly, we found for the first time that neither knockdown nor overexpression of the FAK gene alone caused changes in osteogenesis or osteoclastic function. More importantly, compared with deletion or overexpression of PYK2/FAK alone, coexpression or cosilencing of the two kinases accelerated the effects of TNTs on osteoclastic and osteogenic differentiation on the surface of cells. Furthermore, in vivo experiments revealed a significant increase in positiveexpression-PYK2 cells on the surface of TNTs, but no significant change in positiveexpression -FAK cells was observed. In summary, PYK2 is a key effector molecule by which osteoblasts sense nanotopological mechanical signals and maintain bone homeostasis around implants. These results provide a referable molecular mechanism for the future development and design of homeostasis-based regulatory implant biomaterials.
... Nevertheless, with reference to the discussion presented above, it should be emphasized that the factors analyzed in the presented manuscript, mainly mechanical resistance and incubation fluids, are not the only ones that affect the implanted biomaterial in the body. Biological fluids, besides the considered ions, contain various types of proteins and other active components that can affect the implanted material via surface energy changes, hydrophilic/hydrophobic interactions, and charge changes through cationic/anionic binding [47]. ...
Coating materials offers an intriguing solution for imparting inert implants with additional bioactive characteristics without changing underlying parameters such as mechanical strength. Metallic implants like endoprostheses or polymeric implants can be coated with a thin layer of bioactive film capable of stimulating bone-forming cells to proliferate or release a drug. However, irrespective of the final implantation site of such a coating biomaterial, it is necessary to conduct detailed mechanical and physicochemical in vitro analyses to determine its likely behavior under biological conditions. In this study, polymeric and composite coatings with hydroxyapatite obtained under UV light underwent incubation tests in four different artificial biological fluids: simulated body fluid (SBF), artificial saliva, Ringer’s fluid, and water (as the reference fluid). The potentiometric and conductometric properties, sorption capacity, and degradation rate of the coatings were examined. Furthermore, their hardness, modulus of elasticity, and deformation were determined. It was demonstrated that the coatings remained stable in SBF liquid at a pH value of around 7.4. In artificial saliva, the greatest degradation of the polymer matrix (ranging between 36.19% and 39.79%) and chipping of hydroxyapatite in the composite coatings were observed. Additionally, the effect of ceramics on sorption capacity was determined, with lower capacity noted with higher HA additions. Moreover, the evaluation of surface morphology supported by elemental microanalysis confirmed the appearance of new apatite layers on the surface as a result of incubation in SBF. Ceramics also influenced mechanical aspects, increasing hardness and modulus of elasticity. For the polymer coatings, the value was 11.48 ± 0.61, while for the composite coating with 15% ceramics, it increased more than eightfold to a value of 93.31 ± 11.18 N/mm2. Based on the conducted studies, the effect of ceramics on the physicochemical as well as mechanical properties of the materials was determined, and their behavior in various biological fluids was evaluated. However, further studies, especially cytotoxicity analyses, are required to determine the potential use of the coatings as biomaterials.
