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Schematic diagram of design, application (a), and electric fields (b) generated by Procellera Ò bioelectric dressing. Courtesy of Banerjee et al. 203 Color images available online at www.liebertpub.com/teb
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Progress in biomaterials science and engineering and increasing knowledge in cell biology have enabled us to develop functional biomaterials providing appropriate biochemical and biophysical cues for tissue regeneration applications. Tissue regeneration is particularly important to treat chronic wounds of people with diabetes. Understanding and con...
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... 200,201 In another study, an electrostimulation system (FenzianÔ) was used for a pilot study of 21 diabetic patients with chronic ulcers. Results showed wound area and diameter decreased only in the patients who received the stimulation. 202 A bioelectric dressing that generates physiologic levels of microcurrent (2-10 mA) (Procellera Ò ) (Fig. 4) has been re- ported to accelerate wound healing by promoting re- epithelialization. 203 In another work, a wireless device was used to apply electrical stimulation to treat diabetic foot ulcers 204 by applying microcurrents to the wound surface noninvasively with reduced risk of ...
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Strategies for neural tissue repair heavily depend on our ability to temporally reconstruct the natural cellular microenvironment of neural cells. Biomaterials play a fundamental role in this context, as they provide the mechanical support for cells to attach and migrate to the injury site, as well as fundamental signals for differentiation. This r...
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... The scaffolds are specifically designed to provide essential structural support while promoting tissue regeneration. By mimicking the natural extracellular matrix, they create an environment that encourages cell growth and repair, ultimately assisting the tissue in recovering its functional capabilities [6][7][8]. ...
The addition of oxygen-releasing biomaterials into 3D-printed scaffolds presents a novel approach to enhancing bone scaffolds, yet no in vitro studies have demonstrated the effect of oxygen-generating filaments on scaffold biological and mechanical properties. This study introduces a polylactic acid (PLA)/calcium peroxide (CPO) composite filament, designed for oxygen release, which is a key factor for early-stage bone regeneration. The PLA/CPO composite filament was fabricated via wet-mixing, solvent evaporation, and hot-melt extrusion, followed by fused deposition modeling (FDM) with optimized parameters to achieve high structural fidelity (25% porosity, 0.60mm pore size). In vitro characterization, including mechanical, morphological, and biological assessments, demonstrated that, post-cell culturing, mechanical strength improved, which indicates improved scaffold resilience. The scaffold exhibited gradual oxygen release over a 3-day period, and gene expression analysis confirmed notable upregulation of osteogenic markers RUNX2, SPP1, and SP7 in vitamin D-supplemented conditions. The mechanical strength improved from approximately 2.8 MPa in the control group to 5.0 MPa in scaffolds cultured with osteogenic media. This study provides the first in vitro evidence that oxygen-releasing 3D-printed filaments can improve both mechanical properties and biological response in scaffolds, demonstrating the functional integration of sustained oxygen delivery, enhanced mechanical properties, and increased osteogenic activity in a single 3D-printed scaffold.
... Для этого необходимо решить целый ряд существенных технологических проблем. Получаемые трехмерные печатные конструкции статичны, они не способны воспроизводить натуральную динамическую природу ткани -процессы естественной регенерации и восстановления, которые включают конформационные изменения в структуре [120]. Предстоит совершенствовать характеристики биоматериалов, способных поддерживать пролиферацию и дифференциацию клеток [121][122][123]. ...
Three-dimensional (3D) printing is a method of creating a material object layer-by-layer in space from a virtual, mathematical model. 3D printing is based on additive technologies – a step-by-step formation of a structure by adding material to the base. 3D bioprinting is the fabrication of functional biological structures that mimic human organs and tissues. Analysis of scientific publications showed that in the near future, viable and fully functional artificial copies of individual human organs and tissues can be obtained.
... Tissue engineering presents a potential solution to these challenges by creating a bone scaffold using stem cells, biocompatible materials, growth factors, and biodegradable materials to improve bone fracture healing [4]. These bone scaffolds are designed to supply the required physical support and foster tissue regrowth, leading to the recovery of functionality [5][6][7]. ...
The latest advancements in bone scaffold technology have introduced novel biomaterials that have the ability to generate oxygen when implanted, improving cell viability and tissue maturation. In this paper, we present a new oxygen-generating polylactic acid (PLA)/calcium peroxide (CPO) composite filament that can be used in 3D printing scaffolds. The composite material was prepared using a wet solution mixing method, followed by drying and hot melting extrusion. The concentration of calcium peroxide in the composite varied from 0% to 9%. The prepared filaments were characterized in terms of the presence of calcium peroxide, the generated oxygen release, porosity, and antibacterial activities. Data obtained from scanning electron microscopy and X-ray diffraction showed that the calcium peroxide remained stable in the composite. The maximum calcium and oxygen release was observed in filaments with a 6% calcium peroxide content. In addition, bacterial inhibition was achieved in samples with a calcium peroxide content of 6% or higher. These results indicate that an optimized PLA filament with a 6% calcium peroxide content holds great promise for improving bone generation through bone cell oxygenation and resistance to bacterial infections.
... Four-dimensional (4D) printing is a newer facet of 3D printing from which it was developed. It arises from the necessity of better mimicking the dynamic nature of living tissues and assessing the necessity of conformational changes in tissue regeneration [134]. 4D printed structures entail the ability of shape transformation. ...
Three-dimensional printing has risen in recent years as a promising approach that fast-tracked the biofabrication of tissue engineering constructs that most resemble utopian tissue/organ replacements for precision medicine. Additionally, by using human-sourced biomaterials engineered towards optimal rheological proprieties of extrudable inks, the best possible scaffolds can be created. These can encompass native structure and function with a low risk of rejection, enhancing overall clinical outcomes; and even be further optimized by engaging in information- and computer-driven design workflows. This paper provides an overview of the current efforts in achieving ink’s necessary rheological and print performance proprieties towards biofabrication from human-derived biomaterials. The most notable step for arranging such characteristics to make biomaterials inks are the employed crosslinking strategies, for which examples are discussed. Lastly, this paper illuminates the state-of-the-art of the most recent literature on already used human-sourced inks; with a final emphasis on future perspectives on the field.
... This method involves the creation of a bone scaffold that includes growth factors, stem cells, and biocompatible and biodegradable materials, which can aid in bone fracture healing and enhance the incorporation of the graft [4,5]. The scaffolds are designed to offer physical support and promote tissue regeneration, thereby helping the tissue to recover its functionality [6][7][8]. ...
... Skin is the largest organ of the human body and is responsible for several biological functions, such as: (i) serving as an external barrier for pathogens, (ii) the maintenance of humidity and temperature of adjacent tissues, (iii) water secretion, and so forth (Bacakova et al., 2020). In this sense, chronic wounds are known to affect about 70 million people worldwide, thus being a major problem in contemporary society (Xiao, Ahadian, & Radisic, 2017), as they can lead to a decrease in life-quality, amputations, and even death (Homaeigohar & The preference for naturally-derived antimicrobial agents in biomedical applications relies on the fact that microorganisms cannot generate resistance to them as they are natural substances (Kumar, Lee, Beyenal, & Lee, 2020). Naturally-derived antimicrobial agents include vegetal and essential oils, antimicrobial peptides and fatty acids (Aslanli, Lyagin, Stepanov, Presnov, & Efremenko, 2020;Casillas-Vargas et al., 2021;Lalouckova et al., 2021;Pereira dos Santos et al., 2019;Sekar, Paul, Srinivasan, & Rajasekaran, 2021). ...
Chronic wounds are a big challenge in contemporary society, as they lead to a decrease in life-quality, amputations and even death. Infections and biofilm formation might occur with chronic wounds, due to the higher susceptibility to antibiotic multi-resistant bacteria. In this situation, novel wound dressing biomaterials are needed for treatment. Thus, the aim of this research was to evaluate a possible BNC interaction with tucumã oil/butter-derived fatty acids, as this system could be a promising biomaterial for wound treating. The interaction between cellobiose (BNC basic unit) and four fatty acids was evaluated by ab initio simulations and density functional theory (DFT), through SIESTA code. Molecular docking was also used to investigate the effect of a possible releasing of the studied fatty acids to the quorum-sensing proteins of Pseudomonas aeruginosa (gram-negative bacterium) and Staphylococcus aureus (gram-positive bacterium). According to ab initio simulations, the interaction between cellobiose and fatty acids derived from tucumã oil/butter was suggested due to physical adsorption (energy around 0.17-1.33 eV) of the lipidic structures into cellobiose. A great binding affinity (∆G ranging from 4.2-8.2 kcal.mol-1) was observed for both protonated and deprotonated fatty acids against P. aeruginosa (LasI, LasA and Rhlr) and S. aureus (ArgA and ArgC) quorum-sensing proteins, indicating that these bioactive compounds might act as potential antimicrobial and/or antibiofilm agents in the proposed system. Hence, from a theoretical viewpoint, the proposed system could be a promising raw biomaterial in the production of chronic wound dressings.
... Therefore, utilizing NO to modify the scaffold can improve antithrombotic ability by reducing cell adhesion and proliferation, which can be used as a coating material for repairing vascular injury. However, the instability of NO and its oxidation potential to the toxic nitrogen dioxide molecule is still the barrier to extremely exploit the therapeutic effects of NO (Xiao et al., 2017). So, the development of a more secure and stable delivery system becomes a breakthrough of the next-generation NO-based biomaterials. ...
Mesenchymal stem cells (MSCs) have been widely used in the fields of tissue engineering and regenerative medicine due to their self-renewal capabilities and multipotential differentiation assurance. However, capitalizing on specific factors to precisely guide MSC behaviors is the cornerstone of biomedical applications. Fortunately, several key biophysical and biochemical cues of biomaterials that can synergistically regulate cell behavior have paved the way for the development of cell-instructive biomaterials that serve as delivery vehicles for promoting MSC application prospects. Therefore, the identification of these cues in guiding MSC behavior, including cell migration, proliferation, and differentiation, may be of particular importance for better clinical performance. This review focuses on providing a comprehensive and systematic understanding of biophysical and biochemical cues, as well as the strategic engineering of these signals in current scaffold designs, and we believe that integrating biophysical and biochemical cues in next-generation biomaterials would potentially help functionally regulate MSCs for diverse applications in regenerative medicine and cell therapy in the future.
... Tissue engineering has emerged as a way to address these shortcomings, in which tissue-like structures are used as grafts for implantation [3]. Upon implantation, the engineered tissue is meant to provide the required physical support and stimulate regeneration of tissues, leading to their functional recovery [4][5][6]. ...
Lack of suitable auto/allografts has been delaying surgical interventions for the treatment of numerous disorders and has also caused a serious threat to public health. Tissue engineering could be one of the best alternatives to solve this issue. However, deficiency of oxygen supply in the wounded and implanted engineered tissues, caused by circulatory problems and insufficient angiogenesis, has been a rate-limiting step in translation of tissue-engineered grafts. To address this issue, we designed oxygen-releasing electrospun composite scaffolds, based on a previously developed hybrid polymeric matrix composed of poly(glycerol sebacate) (PGS) and poly(ε-caprolactone) (PCL). By performing ball-milling, we were able to embed a large percent of calcium peroxide (CP) nanoparticles into the PGS/PCL nanofibers able to generate oxygen. The composite scaffold exhibited a smooth fiber structure, while providing sustainable oxygen release for several days to a week, and significantly improved cell metabolic activity due to alleviation of hypoxic environment around primary bone-marrow-derived mesenchymal stem cells (BM-MSCs). Moreover, the composite scaffolds also showed good antibacterial performance. In conjunction to other improved features, such as degradation behavior, the developed scaffolds are promising biomaterials for various tissue-engineering and wound-healing applications.
... Strikingly, the fast-relaxing hydrogel without encapsulated MSCs significantly promoted new bone formation, suggesting that pure mechanical cues from the fast-relaxing hydrogels promoted cell invasion and bone regeneration. These studies showed that the viscoelastic property of biomaterials, as well as chemical and biological cues [221] , are effective regulators of cell processes in vivo and could be leveraged for superior tissue regeneration. ...
Viscoelasticity of living tissues plays a critical role in tissue homeostasis and regeneration, and its implication in disease development and progression is being recognized recently. In this review, we first explored the state of knowledge regarding the potential application of tissue viscoelasticity in disease diagnosis. In order to better characterize viscoelasticity with local resolution and non-invasiveness, emerging characterization methods have been developed with the potential to be supplemented to existing facilities. To understand cellular responses to matrix viscoelastic behaviors in vitro, hydrogels made of natural polymers have been developed and the relationships between their molecular structure and viscoelastic behaviors, are elucidated. Moreover, how cells perceive the viscoelastic microenvironment and cellular responses including cell attachment, spreading, proliferation, differentiation and matrix production, have been discussed. Finally, some future perspective on an integrated mechanobiological comprehension of the viscoelastic behaviors involved in tissue homeostasis, cellular responses and biomaterial design are highlighted.
Statement of Significance
Tissue- or organ-scale viscoelastic behavior is critical for homeostasis, and the molecular basis and cellular responses of viscoelastic materials at micro- or nano-scale are being recognized recently. We summarized the potential applications of viscoelasticity in disease diagnosis enabled by emerging non-invasive characterization technologies, and discussed the underlying mechanism of viscoelasticity of hydrogels and current understandings of cell regulatory functions of them. With a growing understanding of the molecular basis of hydrogel viscoelasticity and recognition of its regulatory functions on cell behaviors, it is important to bring the clinical insights on how these characterization technologies and engineered materials may contribute to disease diagnosis and treatment. This review explains the basics in characterizing viscoelasticity with our hope to bridge the gap between basic research and clinical applications.
... There are over 6.5 million patients suffering from chronic wounds globally and the annual health care costs are over 25 billion US dollars [2]. Different from acute wounds which usually heal simultaneously or in a short time after therapy, there is still a lack of effective treatment for chronic wounds [1]. Some strategies have been developed for accelerating chronic wound healing through biochemical and biophysical cues such as the application of growth factors [3,4], siRNA [5], microRNA [6] and negative pressure [7], but the therapeutic outcomes still need further improvement [8]. ...
Electrical stimulation (ES) via electrodes is promising for treating chronic wounds, but this electrode-based strategy is unable to stimulate the whole wound area and the therapeutic outcome may be compromised. In this study, a conductive poly(2-hydroxyethyl methacrylate) (polyHEMA)/polypyrrole (PPY) hydrogel was developed, and 3-sulfopropyl methacrylate was covalently incorporated in the hydrogel’s network to in-situ dope the PPY and maintain the hydrogel’s conductivity in the weak alkaline physiological environment. The obtained hydrogel was superior to the commercial Hydrosorb® dressing for preventing bacterial adhesion and protein absorption, and this is helpful to reduce the possibilities of infection and secondary damage during dressing replacement. The in vitro scratch assay demonstrates that ES through the hydrogel enhanced fibroblast migration, and this enhancement effect remained even after the ES was ended. The in vivo assay using diabetic rats shows that when ES was conducted with this polyHEMA/PPY hydrogel, the healing rate was faster than that achieved by the electrode-based ES strategy. Therefore, this polyHEMA/PPY hydrogel shows a great potential for developing the next generation of ES treatment for chronic wounds.
Statement of Significance
Electrical stimulation (ES) via separated electrodes is promising for treating chronic wounds, but this electrode-based strategy is unable to stimulate the whole wound area, compromising the therapeutic outcome. Herein, a hydrogel was developed with stable electrical conductivity in the physiological environment and strong resistance to protein absorption and bacterial adhesion. The in vitro and in vivo tests proved that ES applied through the flexible and conductive hydrogel that covered the wound was superior to ES through electrodes for promoting the healing of the chronic wound. This hydrogel-based ES strategy combines the advantages of ES and hydrogel dressing and will pave the way for the next generation of ES treatment for chronic wounds.
