Cellulose is the most abundant polysaccharide on Earth. It can be obtained from a vast number of sources,
e.g.
cell walls of wood and plants, some species of bacteria, and algae, as well as ...tunicates, which are the only known cellulose-containing animals. This inherent abundance naturally paves the way for discovering new applications for this versatile material. This review provides an extensive survey on cellulose and its derivatives, their structural and biochemical properties, with an overview of applications in tissue engineering, wound dressing, and drug delivery systems. Based on the available means of selecting the physical features, dimensions, and shapes, cellulose exists in the morphological forms of fiber, microfibril/nanofibril, and micro/nanocrystalline cellulose. These different cellulosic particle types arise due to the inherent diversity among the source of organic materials or due to the specific conditions of biosynthesis and processing that determine the consequent geometry and dimension of cellulosic particles. These different cellulosic particles, as building blocks, produce materials of different microstructures and properties, which are needed for numerous biomedical applications. Despite having great potential for applications in various fields, the extensive use of cellulose has been mainly limited to industrial use, with less early interest towards the biomedical field. Therefore, this review highlights recent developments in the preparation methods of cellulose and its derivatives that create novel properties benefiting appropriate biomedical applications.
Chitin the second most abundant polysaccharide is synthesized by an enormous number of living organisms including fungi and insects. These biopolymers have found many applications in different areas ...such as: packaging material, membrane for removal of metal ions, dyes and pigments in waste water engineering; anti-cholesterol, fat binding, preservative and food additive in food industry; seed and fertilizer coating, controlled agrochemical release in agriculture; surface treatment, photographic paper in pulp and paper industry; moisturizer, body creams and lotions in cosmetics and toiletries. It has also found wide applications in biomedical such as tissue engineering, drug delivery, wound dressing, scaffolds, cancer diagnosis, etc. The majority of these versatile applications are coming of its non-toxicity, biocompatibility and biodegradability. Chitin is also easily processed as gel, membrane, and nanofiber. This review emphasizes an extensive bibliography of recent basic and applied research and investigations on the aspects of this interesting biopolymer including the recovery, preparation, modification and application of chitin and its derivatives and related compounds. A new class of biocompatible and biodegradable chitin-based polyurethane (PU) elastomer was also introduced and reviewed in this study and it was found that by incorporation of chitin into the PU elastomer backbone, biocompatibility and degradation rate of the final elastomer improved. PUs are one of the synthetic biocompatible polymers with excellent physical and mechanical properties. Combination of this polymer with chitin resulted to a new tailor-made biocompatible and biodegradable polymer with improved properties. These polymers have potential applications in various applications including biomedical.
Iron corrosion in acidic media is a natural phenomenon that converts elemental iron to a more chemically-stable form, i.e. its oxide and hydroxide. In this study, the iron corrosion process is ...modeled as a completely implicit problem, solved by a novel finite difference model to provide insight into the ionic aspects of corrosion behavior. This new mathematical model eliminates the chemical potential parameters from the corrosion process equations, thereby reducing the need for experimental determination of chemical potentials. The eliminated-chemical-potential-parameters model predicts and quantifies key parameters (concentrations of conjugate base ion, iron (II) ion, hydrogen ion, anodic and cathodic potentials, and the electrical current density) associated with the iron corrosion process in acidic solutions. The rigorous derivation and novel application of the eliminated-chemical-potential-parameters model and its results provide new insights into the iron corrosion process. The present model is also applicable in any industrial process which is associated with metal corrosion. The model helps to guide the design of future corrosion resistant systems, and various experimental studies pertaining to corrosion inhibition techniques.
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The lack of bioactivity in three-dimensional (3D)-printing of poly-є-caprolactone (PCL) scaffolds limits cell-material interactions in bone tissue engineering. This constraint can be overcome by ...surface-functionalization using glycosaminoglycan-like anionic polysaccharides, e.g., carboxymethyl cellulose (CMC), a plant-based carboxymethylated, unsulfated polysaccharide, and κ-carrageenan, a seaweed-derived sulfated, non-carboxymethylated polysaccharide. The sulfation of CMC and carboxymethylation of κ-carrageenan critically improve their bioactivity. However, whether sulfated carboxymethyl cellulose (SCMC) and carboxymethyl κ-carrageenan (CM-κ-Car) affect the osteogenic differentiation potential of pre-osteoblasts on 3D-scaffolds is still unknown. Here, we aimed to assess the effects of surface-functionalization by SCMC or CM-κ-Car on the physicochemical and mechanical properties of 3D-printed PCL scaffolds, as well as the osteogenic response of pre-osteoblasts. MC3T3-E1 pre-osteoblasts were seeded on 3D-printed PCL scaffolds that were functionalized by CM-κ-Car (PCL/CM-κ-Car) or SCMC (PCL/SCMC), cultured up to 28 days. The scaffolds’ physicochemical and mechanical properties and pre-osteoblast function were assessed experimentally and by finite element (FE) modeling. We found that the surface-functionalization by SCMC and CM-κ-Car did not change the scaffold geometry and structure but decreased the elastic modulus. Furthermore, the scaffold surface roughness and hardness increased and the scaffold became more hydrophilic. The FE modeling results implied resilience up to 2% compression strain, which was below the yield stress for all scaffolds. Surface-functionalization by SCMC decreased
Runx2
and
Dmp1
expression, while surface-functionalization by CM-κ-Car increased
Cox2
expression at day 1. Surface-functionalization by SCMC most strongly enhanced pre-osteoblast proliferation and collagen production, while CM-κ-Car most significantly increased alkaline phosphatase activity and mineralization after 28 days. In conclusion, surface-functionalization by SCMC or CM-κ-Car of 3D-printed PCL-scaffolds enhanced pre-osteoblast proliferation and osteogenic activity, likely due to increased surface roughness and hydrophilicity. Surface-functionalization by SCMC most strongly enhanced cell proliferation, while CM-κ-Car most significantly promoted osteogenic activity, suggesting that surface-functionalization by CM-κ-Car may be more promising, especially in the short-term, for
in vivo
bone formation.
Purpose of Review
Orthodontic tooth movement is characterized by periodontal tissue responses to mechanical loading, leading to clinically relevant functional adaptation of jaw bone. Since osteocytes ...are significant in mechanotransduction and orchestrate osteoclast and osteoblast activity, they likely play a central role in orthodontic tooth movement. In this review, we attempt to shed light on the impact and role of osteocyte mechanotransduction during orthodontic tooth movement.
Recent Findings
Mechanically loaded osteocytes produce signaling molecules, e.g., bone morphogenetic proteins, Wnts, prostaglandins, osteopontin, nitric oxide, sclerostin, and RANKL, which modulate the recruitment, differentiation, and activity of osteoblasts and osteoclasts. The major signaling pathways activated by mechanical loading in osteocytes are the wingless-related integration site (Wnt)/β-catenin and RANKL pathways, which are key regulators of bone metabolism. Moreover, osteocytes are capable of orchestrating bone adaptation during orthodontic tooth movement.
Summary
A better understanding of the role of osteocyte mechanotransduction is crucial to advance orthodontic treatment. The optimal force level on the periodontal tissues for orthodontic tooth movement producing an adequate biological response, is debated. This review emphasizes that both mechanoresponses and inflammation are essential for achieving tooth movement clinically. To fully comprehend the role of osteocyte mechanotransduction in orthodontic tooth movement, more knowledge is needed of the biological pathways involved. This will contribute to optimization of orthodontic treatment and enhance patient outcomes.
A challenging approach of three-dimensional (3D)-biomimetic scaffold design for bone tissue engineering is to improve scaffold bioactivity and mechanical properties. We aimed to design and fabricate ...3D-polycaprolactone (PCL)-based nanocomposite scaffold containing a high concentration homogeneously distributed carbonated-nanohydroxyapatite (C-nHA)-particles in combination with immobilized-collagen to mimic real bone properties. PCL-scaffolds without/with C-nHA at 30%, 45%, and 60% (wt/wt) were 3D-printed. PCL/C-nHA60%-scaffolds were surface-modified by NaOH-treatment and collagen-immobilization. Physicomechanical and biological properties were investigated experimentally and by finite-element (FE) modeling. Scaffold surface-roughness enhanced by increasing C-nHA (1.7 - 6.1-fold), but decreased by surface-modification (0.6-fold). The contact angle decreased by increasing C-nHA (0.9 - 0.7-fold), and by surface-modification (0.5-fold). The zeta potential decreased by increasing C-nHA (3.2-9.9-fold). Average elastic modulus, compressive strength, and reaction force enhanced by increasing C-nHA and by surface-modification. FE modeling revealed that von Mises stress distribution became less homogeneous by increasing C-nHA, and by surface-modification. Maximal von Mises stress for 2% compression strain in all scaffolds did not exceed yield stress for bulk-material. 3D-printed PCL/C-nHA60% with surface-modification enhanced pre-osteoblast spreading, proliferation, collagen deposition, alkaline phosphatase activity, and mineralization. In conclusion, a novel biomimetic 3D-printed PCL-scaffold containing a high concentration C-nHA with surface-modification was successfully fabricated. It exhibited superior physicomechanical and biological properties, making it a promising biomaterial for bone tissue engineering.
In bone tissue engineering, prediction of forces induced to the native bone during normal functioning is important in the design, fabrication, and integration of a scaffold with the host. The aim of ...this study was to customize the mechanical properties of a layer-by-layer 3D-printed poly(ϵ-caprolactone) (PCL) scaffold estimated by finite element (FE) modeling in order to match the requirements of the defect, to prevent mechanical failure, and ensure optimal integration with the surrounding tissue. Forces and torques induced on the mandibular symphysis during jaw opening and closing were predicted by FE modeling. Based on the predicted forces, homogeneous-structured PCL scaffolds with 3 different void sizes (0.3, 0.6, and 0.9 mm) were designed and 3D-printed using an extrusion based 3D-bioprinter. In addition, 2 gradient-structured scaffolds were designed and 3D-printed. The first gradient scaffold contained 2 regions (0.3 mm and 0.6 mm void size in the upper and lower half, respectively), whereas the second gradient scaffold contained 3 regions (void sizes of 0.3, 0.6, and 0.9 mm in the upper, middle and lower third, respectively). Scaffolds were tested for their compressive and tensile strength in the upper and lower halves. The actual void size of the homogeneous scaffolds with designed void size of 0.3, 0.6, and 0.9 mm was 0.20, 0.59, and 0.95 mm, respectively. FE modeling showed that during opening and closing of the jaw, the highest force induced on the symphysis was a compressive force in the transverse direction. The compressive force was induced throughout the symphyseal line and reduced from top (362.5 N, compressive force) to bottom (107.5 N, tensile force) of the symphysis. Compressive and tensile strength of homogeneous scaffolds decreased by 1.4-fold to 3-fold with increasing scaffold void size. Both gradient scaffolds had higher compressive strength in the upper half (2 region-gradient scaffold: 4.9 MPa; 3 region-gradient scaffold: 4.1 MPa) compared with the lower half (2 region-gradient scaffold: 2.5 MPa; 3 region-gradient scaffold: 2.7 MPa) of the scaffold. 3D-printed PCL scaffolds had higher compressive strength in the scaffold layer-by-layer building direction compared with the side direction, and a very low tensile strength in the scaffold layer-by-layer building direction. Fluid shear stress and fluid pressure distribution in the gradient scaffolds were more homogeneous than in the 0.3 mm void size scaffold and similar to the 0.6 mm and 0.9 mm void size scaffolds. In conclusion, these data show that the mechanical properties of 3D-printed PCL scaffolds can be tailored based on the predicted forces on the mandibular symphysis. These 3D-printed PCL scaffolds had different mechanical properties in scaffold building direction compared with the side direction, which should be taken into account when placing the scaffold in the defect site. Our findings might have implications for improved performance and integration of scaffolds with native tissue.
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•Jaw opening induced higher compression to upper versus lower parts of the symphysis.•All scaffolds had higher compressive strength in building versus side direction.•Gradient scaffolds had higher compressive strength in upper versus lower half.•Gradient scaffolds fit the force distribution in the symphysis during jaw opening.•Fluid shear stress and pressure were rather homogeneous in the gradient scaffolds.
Bioreactor systems, for example, spinner flask and perfusion bioreactors, and cell-seeded three-dimensional (3D)-printed scaffolds are used in bone tissue engineering strategies to stimulate cells ...and produce bone tissue suitable for implantation into the patient. The construction of functional and clinically relevant bone graft using cell-seeded 3D-printed scaffolds within bioreactor systems is still a challenge. Bioreactor parameters, for example, fluid shear stress and nutrient transport, will crucially affect cell function on 3D-printed scaffolds. Therefore, fluid shear stress induced by spinner flask and perfusion bioreactors might differentially affect osteogenic responsiveness of pre-osteoblasts inside 3D-printed scaffolds. We designed and fabricated surface-modified 3D-printed poly-ɛ-caprolactone (PCL) scaffolds, as well as static, spinner flask, and perfusion bioreactors to determine fluid shear stress and osteogenic responsiveness of MC3T3-E1 pre-osteoblasts seeded on the scaffolds in the bioreactors using finite element (FE)-modeling and experiments. FE-modeling was used to quantify wall shear stress (WSS) distribution and magnitude inside 3D-printed PCL scaffolds within spinner flask and perfusion bioreactors. MC3T3-E1 pre-osteoblasts were seeded on NaOH surface-modified 3D-printed PCL scaffolds, and cultured in customized static, spinner flask, and perfusion bioreactors up to 7 days. The scaffolds' physicochemical properties and pre-osteoblast function were assessed experimentally. FE-modeling showed that spinner flask and perfusion bioreactors locally affected WSS distribution and magnitude inside the scaffolds. The WSS distribution was more homogeneous inside scaffolds in perfusion than in spinner flask bioreactors. The average WSS on scaffold-strand surfaces ranged from 0 to 6.5 mPa for spinner flask bioreactors, and from 0 to 4.1 mPa for perfusion bioreactors. Surface modification of scaffolds by NaOH resulted in a surface with a honeycomb-like pattern and increased surface roughness (1.6-fold), but decreased water contact angle (0.3-fold). Both spinner flask and perfusion bioreactors increased cell spreading, proliferation, and distribution throughout the scaffolds. Perfusion, but not spinner flask bioreactors more strongly enhanced collagen (2.2-fold) and calcium deposition (2.1-fold) throughout the scaffolds after 7 days compared with static bioreactors, likely due to uniform WSS-induced mechanical stimulation of the cells revealed by FE-modeling. In conclusion, our findings indicate the importance of using accurate FE models to estimate WSS and determine experimental conditions for designing cell-seeded 3D-printed scaffolds in bioreactor systems. Impact Statement The success of cell-seeded three-dimensional (3D)-printed scaffolds depends on cell stimulation by biomechanical/biochemical factors to produce bone tissue suitable for implantation into the patient. We designed and fabricated surface-modified 3D-printed poly-ɛ-caprolactone (PCL) scaffolds, as well as static, spinner flask, and perfusion bioreactors to determine wall shear stress (WSS) and osteogenic responsiveness of pre-osteoblasts seeded on the scaffolds using finite element (FE)-modeling and experiments. We found that cell-seeded 3D-printed PCL scaffolds within perfusion bioreactors more strongly enhanced osteogenic activity than within spinner flask bioreactors. Our results indicate the importance of using accurate FE-models to estimate WSS and determine experimental conditions for designing cell-seeded 3D-printed scaffolds in bioreactor systems.
Muscle stem cells (MuSCs) are involved in muscle maintenance and regeneration. Mechanically loaded MuSCs within their native niche undergo tensile and shear deformations, but how MuSCs sense ...mechanical stimuli and translate these into biochemical signals regulating function and fate is still poorly understood. We aimed to investigate whether the glycocalyx is involved in the MuSC mechanoresponse, and whether MuSC morphology affects mechanical loading-induced pressure, shear stress, and fluid velocity distribution. FSS-induced deformation of active proliferating MuSCs (myoblasts) with intact or degraded glycocalyx was assessed by live-cell imaging. Glycocalyx-degradation did not significantly affect nitric oxide production, but reduced FSS-induced myoblast deformation and modulated gene expression. Finite-element analysis revealed that the distribution of FSS-induced pressure, shear stress, and fluid velocity on myoblasts was non-uniform, and the magnitude depended on myoblast morphology and apex-height. In conclusion, our results suggest that the glycocalyx does not play a role in NO production in myoblasts but might impact mechanotransduction and gene expression, which needs further investigation. Future studies will unravel the underlying mechanism by which the glycocalyx affects FSS-induced myoblast deformation, which might be related to increased drag forces. Moreover, MuSCs with varying apex-height experience different levels of FSS-induced pressure, shear stress, and fluid velocity, suggesting differential responsiveness to fluid shear forces.
•The glycocalyx is involved in mechanotransduction by myoblasts.•The glycocalyx is involved in fluid shear stress-induced gene expression.•Nitric oxide production is independent of an intact glycocalyx in myoblasts.•MuSC apex-height determines fluid shear stress-induced shear stress distribution.
Muscle stem cells (MuSCs) are requisite for skeletal muscle regeneration and homeostasis. Proper functioning of MuSCs, including activation, proliferation, and fate decision, is determined by an ...orchestrated series of events and communication between MuSCs and their niche. A multitude of biochemical stimuli are known to regulate MuSC fate and function. However, in addition to biochemical factors, it is conceivable that MuSCs are subjected to mechanical forces during muscle stretch-shortening cycles because of myofascial connections between MuSCs and myofibers. MuSCs respond to mechanical forces in vitro, but it remains to be proven whether physical forces are also exerted on MuSCs in their native niche and whether they contribute to the functioning and fate of MuSCs. MuSC deformation in their native niche resulting from mechanical loading of ex vivo myofiber bundles was visualized utilizing mT/mG double-fluorescent Cre-reporter mouse and multiphoton microscopy. MuSCs were subjected to 1 h pulsating fluid shear stress (PFSS) with a peak shear stress rate of 6.5 Pa/s. After PFSS treatment, nitric oxide, messenger RNA (mRNA) expression levels of genes involved in regulation of MuSC proliferation and differentiation, ERK 1/2, p38, and AKT activation were determined. Ex vivo stretching of extensor digitorum longus and soleus myofiber bundles caused compression as well as tensile and shear deformation of MuSCs in their niche. MuSCs responded to PFSS in vitro with increased nitric oxide production and an upward trend in iNOS mRNA levels. PFSS enhanced gene expression of c-Fos, Cdk4, and IL-6, whereas expression of Wnt1, MyoD, Myog, Wnt5a, COX2, Rspo1, Vangl2, Wnt10b, and MGF remained unchanged. ERK 1/2 and p38 MAPK signaling were also upregulated after PFSS treatment. We conclude that MuSCs in their native niche are subjected to force-induced deformations due to myofiber stretch-shortening. Moreover, MuSCs are mechanoresponsive, as evidenced by PFSS-mediated expression of factors by MuSCs known to promote proliferation.
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