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From fibrinogen to fibrin Mesh. (A) Fibrinogen D:E:D regions interact with thrombin-realizing fibrinopeptides (FpA and FpB) (B). Soluble fibrin is then activated by Factor XIIIa, permitting sulfide bonding to crosslink among fibrin, converting it to a (C) crosslinked fibrin polymer.
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Articular cartilage is a highly organized tissue that provides remarkable load-bearing and low friction properties, allowing for smooth movement of diarthrodial joints; however, due to the avascular, aneural, and non-lymphatic characteristics of cartilage, joint cartilage has self-regeneration and repair limitations. Cartilage tissue engineering is...
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Purpose
Patellar cartilage lesions are a frequent and challenging finding in orthopaedic clinical practice. This study aimed to evaluate a chitosan‐based scaffold's mid‐term clinical and imaging results patients with patellar cartilage lesions.
Methods
Thirteen patients (nine men, four women, 31.3 ± 12.7 years old) were clinically evaluated prospe...
Articular cartilage damage and wear can result in cartilage degeneration, ultimately culminating in osteoarthritis. Current surgical interventions offer limited capacity for cartilage tissue regeneration and offer only temporary alleviation of symptoms. Tissue engineering strategies are increasingly recognized as promising modalities for cartilage...
Irregular articular cartilage injury is a common type of joint trauma, often resulting from intense impacts and other factors that lead to irregularly shaped wounds, the limited regenerative capacity of cartilage and the mismatched shape of the scaffods have contributed to unsatisfactory therapeutic outcomes. While injectable materials are a tradit...
Regenerative cartilage replacements are increasingly required in clinical settings for various defect repairs, including bronchial cartilage deficiency, articular cartilage injury, and microtia reconstruction. Poly (glycerol sebacate) (PGS) is a widely used bioelastomer that has been developed for various regenerative medicine applications because...
Intrinsically present bioactive cues allow naturally derived materials to mimic important characteristics of cartilage while also facilitating cellular recruitment, infiltration, and differentiation. Such traits are often what tissue engineers desire when they fabricate scaffolds, and yet, literature from the past decade is replete with examples of...
Citations
... In clinical applications, the mechanical properties of the scaffold directly affect its stability and functional outcomes in vivo. Therefore, evaluating and optimizing the mechanical properties of the scaffold is key to ensuring its successful application in tissue engineering and regenerative medicine [119]. ...
Age-related macular degeneration (AMD), a progressive neurodegenerative disorder affecting the central retina, is pathologically defined by the irreversible degeneration of photoreceptors and retinal pigment epithelium (RPE), coupled with extracellular drusen deposition and choroidal neovascularization (CNV), and AMD constitutes the predominant etiological factor for irreversible vision impairment in adults aged ≥60 years. Cell-based or cell-biomaterial scaffold-based approaches have been popular in recent years as a major research direction for AMD; monotherapy with cell-based approaches typically involves subretinal injection of progenitor-derived or stem cell-derived RPE cells to restore retinal homeostasis. Meanwhile, cell-biomaterial scaffolds delivered to the lesion site by vector transplantation have been widely developed, and the implanted cell-biomaterial scaffolds can promote the reintegration of cells at the lesion site and solve the problems of translocation and discrete cellular structure produced by cell injection. While these therapeutic strategies demonstrate preliminary efficacy, rigorous preclinical validation and clinical trials remain imperative to validate their long-term safety, functional durability, and therapeutic consistency. This review synthesizes current advancements and translational challenges in cell-based and cell-biomaterial scaffold approaches for AMD, aiming to inform future development of targeted interventions for AMD pathogenesis and management.
... Fibrin is a byproduct of fibrinogen, which is composed of As, Bβ, and γ peptide chains (Tan et al., 2021). Fibrin is a suitable biomaterial for scaffolds owing to its biocompatibility and ability to bind proteins and growth factors (Rojas-Murillo et al., 2022). However, fibrin produced from human thrombin and fibrinogen has a high production cost (Contessi Negrini et al., 2020). ...
... The synthesized nano-scaffold exhibited an elastic modulus of 3.21 KPa, which closely aligns with the mechanical properties of intact neural tissue (Supplementary Table A). This is a critical parameter, as the stiffness and elasticity of the scaffold must match the target tissue to provide optimal support for cell growth and function [58][59][60][61][62] . ...
Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide, presenting a significant challenge due to the lack of effective therapies. Neural stem cells (NSCs) have shown promising potential in preclinical studies as a therapy for TBI. However, their application is limited by challenges related to poor survival and integration within the injured brain. This study investigated the effect of a novel nano-scaffold containing stromal cell-derived factor 1 (SDF-1) on NSC behavior and synaptogenesis after TBI. Using an innovative design, we successfully fabricated a nano-scaffold with Young’s modulus of approximately 3.21 kPa, which aligns closely with the mechanical properties exhibited by neural tissue. This achievement marks the first time such a scaffold has been created and has promising implications for its potential use in neural tissue engineering applications. Our findings demonstrate that the nano-scaffold enhances NSC proliferation, migration, and differentiation capacity in vitro. Moreover, when transplanted into the injured brain, the nano-scaffold promotes the survival and integration of NSCs, leading to increased synaptogenesis and functional recovery. These findings suggest that using the novel nano-scaffold containing SDF-1 could provide a promising approach to treating TBI by improving NSC behavior and promoting synaptogenesis.
... A large variety of composites consisting of cellulose fibers and polymers have been fabricated using various approaches as scaffolds for tissue engineering (TE). 58,59 However, TE scaffolds fabricated from wood and taking advantage of wood characteristics have not been reported. Although the ability of ...
... Article cellulose-fiber-containing scaffolds to regenerate bone and skin has been evaluated in many studies, in vivo studies assessing their ability to regenerate cartilage are limited. 58,59 Furthermore, cellulose fiber-containing scaffolds used for cartilage TE exhibit insufficient mechanical strength, poor structural stability, and uncontrolled pore size and connectivity. 58,59 In this study, the skeletal structure of wood enhances structural stability, ensures controlled pore size, and improves pore connectivity. ...
... 58,59 Furthermore, cellulose fiber-containing scaffolds used for cartilage TE exhibit insufficient mechanical strength, poor structural stability, and uncontrolled pore size and connectivity. 58,59 In this study, the skeletal structure of wood enhances structural stability, ensures controlled pore size, and improves pore connectivity. Moreover, the hydrogel acquires a mechanical strength equivalent to that of cartilage following the intervention with CA and NAG. ...
Repairing cartilage tissue is a serious global challenge. Herein, we focus on wood skeletal structures that are highly porous for cell penetration yet have load-bearing strength, and aim to synthesize wood-derived hydrogels with the ability to regenerate cartilage tissues. The hydrogels were synthesized by wood delignification and the subsequent intercalation of citric acid (CA), which is involved in tricarboxylic acid cycles and essential for energy production, and N-acetylglucosamine (NAG), which is a cartilage glycosaminoglycan, among cellulose microfibrils. CA and NAG intercalation increased the amorphous region of the cellulose microfibrils and endowed them with flexibility while maintaining the skeletal structure of the wood. Consequently, the CA-NAG-treated wood hydrogels became twistable and bendable, and the acquired stiffness, compressive strength, water content, and cushioning characteristics were similar to those of the cartilage. In rabbit femur cartilage defects, CA-NAG-treated wood hydrogels induced the differentiation of surrounding cells into chondrocytes. Consequently, the CA-NAG-treated wood hydrogels repaired cartilage defects, whereas the collagen scaffolds, delignified wood materials, and CA-treated wood hydrogels did not. The CA-NAG-treated wood hydrogels exhibit superior structural and mechanical characteristics over conventional cellulose-fiber-containing scaffolds. Furthermore, the CA-NAG-treated wood hydrogels can effectively repair cartilage on their own, whereas conventional natural and synthetic polymeric materials need to be combined with cells and growth factors to achieve a sufficient therapeutic effect. Therefore, the CA-NAG-treated wood hydrogels successfully address the limitations of current therapies that either fail to repair articular cartilage or sacrifice healthy cartilage. To our knowledge, this is the pioneer study on the utilization of thinned wood for tissue engineering, which will contribute to solving both global health and environmental problems and to creating a sustainable society.
... It is readily processable, extensively utilized, and regarded as one of the most promising biomaterials in the field of tissue engineering. On one hand, studies have shown that the molecular structure of the Fib hydrogel can improve the biomechanical properties of the material [25]. On the other hand, compared to other hydrogel materials, it can promote coagulation and neovascularization, significantly promoting the in situ regeneration and repair of the meniscus [22,[26][27][28]. ...
... The reasons for the above biochemical analysis results were confirmed at the gene level. Similar to the findings of other studies [25,[54][55][56], the Fib hydrogel promoted cell adhesion and ECM production in the current study. Subsequently, the scaffold was subcutaneously implanted in rats to evaluate the immunogenicity of the scaffold and its ability to promote angiogenesis. ...
... These findings emphasize the role of Fib hydrogel in situ meniscal regeneration. Previous studies have reported better biocompatibility of hydrogel materials to promote ECM production and maturation and remodeling of meniscal tissue [25,64,65]. In the control group, only regeneration of synovial tissue was observed, indicating that the meniscus does not regenerate effectively without intervention. ...
A meniscus injury is a common cartilage disease of the knee joint. Despite the availability of various methods for the treatment of meniscal injuries, the poor regenerative capacity of the meniscus often necessitates resection, leading to the accelerated progression of osteoarthritis. Advances in tissue engineering have introduced meniscal tissue engineering as a potential treatment option. In this study, we established the size of a standardized meniscal scaffold using knee Magnetic Resonance Imaging (MRI) data and created a precise Polycaprolactone (PCL) scaffold utilizing 3-Dimensional (3D) printing technology, which was then combined with Fibrin (Fib) hydrogel to form a PCL-Fib scaffold. The 10.13039/100018919PCL scaffold offers superior biomechanical properties, while the Fib hydrogel creates a conducive microenvironment for cell growth, supporting chondrocyte proliferation and extracellular matrix (ECM) production. Physical and chemical characterization, biocompatibility testing, and in vivo animal experiments revealed the excellent biomechanical properties and biocompatibility of the scaffold, which enhanced in situ meniscal regeneration and reduced osteoarthritis progression. In conclusion, the integration of 3D printing technology and the Fib hydrogel provided a supportive microenvironment for chondrocyte proliferation and ECM secretion, facilitating the in situ regeneration and repair of the meniscal defect. This innovative approach presents a promising avenue for meniscal injury treatment and advances the clinical utilization of artificial meniscal grafts.
... Given the crucial roles of fibrin and fibrinogen in blood clotting, the inflammatory response, and cell-matrix interactions, they do not induce toxic degradation or inflammatory responses [97]. Fibrin forms gels through the enzymatic polymerization of fibrinogen at room temperature in the presence of thrombin, with their degradation rate controllable by aprotinin, a proteinase inhibitor [98]. In the realm of cartilage regeneration, fibrin exhibits inherent biocompatibility and facilitates cellular adhesion, proliferation, and migration within hydrogel scaffolds [99]. ...
Autologous chondrocyte implantation (ACI) and matrix-induced ACI (MACI) have demonstrated improved clinical outcomes and reduced revision rates for treating osteochondral and chondral defects. However, their ability to achieve lasting, fully functional repair remains limited. To overcome these challenges, scaffold-enhanced ACI, particularly utilizing hydrogel-based biomaterials, has emerged as an innovative strategy. These biomaterials are intended to mimic the biological composition, structural organization, and biomechanical properties of native articular cartilage. This review aims to provide comprehensive and up-to-date information on advancements in hydrogel-enhanced ACI from the past decade. We begin with a brief introduction to cartilage biology, mechanisms of cartilage injury, and the evolution of surgical techniques, particularly looking at ACI. Subsequently, we review the diversity of hydrogel scaffolds currently undergoing development and evaluation in preclinical studies for articular cartilage regeneration, emphasizing chondrocyte-laden hydrogels applicable to ACI. Finally, we address the key challenges impeding effective clinical translation, with particular attention to issues surrounding fixation and integration, aiming to inform and guide the future progression of tissue engineering strategies.
... Considering that the layers of composite were intended to mimic bone, greater flexibility is required for the cartilaginous tissue. As we know, the mechanical properties of scaffolds are primarily determined by the interaction between materials and their geometric structure [24]. From these results, it was found that the mechanical properties of the scaffolds containing 30% fibrin are lower than the other scaffolds with fibrin content below 30%. ...
... Fibrin has a faster degradation rate compared to that for PCL and hydroxyapatite due to its intrinsic instability. Thus, by fabricating scaffolds containing fibrin and other biomaterials such as PCL and HA can adjust the degradation rate of scaffold [24]. Figure 7 illustrates the changes in pH over time for scaffolds with different percentages of fibrin. ...
... As shown in Fig. 10A, cell growth on the bilayered scaffolds is higher than the control sample on days 1 and 3, and, it is almost equal to the control sample by day 7. This indicates that the environment is fully saturated, and fibrin has prevented more cells from adhering to the surface [24]. ...
Prolonged osteochondral tissue engineering damage can result in osteoarthritis and decreased quality of life. Multiphasic scaffolds, where different layers model different microenvironments, are a promising treatment approach, yet stable joining between layers during fabrication remains challenging. To overcome this problem, in this study, a bilayer scaffold for osteochondral tissue regeneration was fabricated using 3D printing technology which containing a layer of PCL/hydroxyapatite (HA) nanoparticles and another layer of PCL/gelatin with various concentrations of fibrin (10, 20 and 30 wt.%). These printed scaffolds were evaluated with SEM (Scanning Electron Microscopy), FTIR (Fourier Transform Infrared Spectroscopy) and mechanical properties. The results showed that the porous scaffolds fabricated with pore size of 210–255 µm. Following, the ductility increased with the further addition of fibrin in bilayer composites which showed these composites scaffolds are suitable for the cartilage part of osteochondral. Also, the contact angle results demonstrated the incorporation of fibrin in bilayer scaffolds based on PCL matrix, can lead to a decrease in contact angle and result in the improvement of hydrophilicity that confirmed by increasing the degradation rate of scaffolds containing further fibrin percentage. The bioactivity study of bilayer scaffolds indicated that both fibrin and hydroxyapatite can significantly improve the cell attachment on fabricated scaffolds. The MTT assay, DAPI and Alizarin red tests of bilayer composite scaffolds showed that samples containing 30% fibrin have the more biocompatibility than that of samples with 10 and 20% fibrin which indicated the potential of this bilayer scaffold for osteochondral tissue regeneration.
Graphical Abstract
... The scaffold exhibiting the superior cell distribution and adhesion with the highest cell viability rate in the MTT assay was selected as the optimized sample. Scaffolds must possess adequate load-bearing capability to withstand the mechanical stresses experienced in the patellofemoral joint, ensuring stability and durability throughout the healing process [23,24]. Thus, to further enhance its mechanical properties, a fourth scaffold was produced by printing an additional layer of PCL on top of the existing structure. ...
In this study, polycaprolactone (PCL) scaffolds have been employed as structural framework scaffolds for patellofemoral cartilage tissue regeneration. The biomechanical and biological properties of different scaffolds were investigated by varying alginate concentrations and the number of scaffold layers. Patellofemoral cartilage defects result in knee pain and reduced mobility, and they are usually treated with conventional methods, often with limited success. Generally, tissue-engineered PCL-alginate scaffolds fabricated by bioprinting technology show promise for enhanced cartilage regeneration due to the biocompatibility and mechanical stability of PCL. In addition, alginate is known for its cell encapsulation capabilities and for promoting cell viability. Biological and morphological assessments, utilizing water contact angle, cell adhesion tests, MTT assays, and scanning electron microscopy (SEM), informed the selection of the optimized scaffold. Comparative analyses between the initial optimal scaffolds with the same chemical composition also included flexural and compression tests and fracture surface observations using SEM. The controlled integration of PCL and alginate offers a hybrid approach, that assembles the mechanical strength of PCL and the bioactive properties of alginate for tissue reconstruction potential. This study aims to identify the most effective scaffold composition for patellofemoral articular cartilage tissue engineering, emphasizing cell viability, structural morphology, and mechanical integrity. The results showed that the optimum biomechanical and biological properties of scaffolds were obtained with a 10% alginate concentration in the monolayer of PCL structure. The findings contribute to regenerative medicine by advancing the understanding of functional tissue constructs, bringing us closer to addressing articular cartilage defects and related clinical challenges.
... Substrates play a crucial role in bioengineering by providing a biomimetic environment [1][2][3][4] and by enhancing various biological functions through interactions with biological materials [5,6]. Various polymers and hydrogels are widely used as substrate materials, including polyethylene (PE) [7], polypropylene (PP) [8], polytetrafluoroethylene (PTEF) [9], polymethylmethacrylate (PMMA) [10], polydimethylsiloxane (PDMS) [11,12], collagen [13], fibrin [14], and Matrigel [15]. These materials can be categorized into soft and hard substrates based on their physical and chemical properties and can be mixed to create hybrid substrates for improved functionality. ...
The surface topography of substrates is a crucial factor that determines the interaction with biological materials in bioengineering research. Therefore, it is important to appropriately modify the surface topography according to the research purpose. Surface topography can be fabricated in various forms, such as wrinkles, creases, and ridges using surface deformation techniques, which can contribute to the performance enhancement of cell chips, organ chips, and biosensors. This review provides a comprehensive overview of the characteristics of soft, hard, and hybrid substrates used in the bioengineering field and the surface deformation techniques applied to the substrates. Furthermore, this review summarizes the cases of cell-based research and other applications, such as biosensor research, that utilize surface deformation techniques. In cell-based research, various studies have reported optimized cell behavior and differentiation through surface deformation, while, in the biosensor and biofilm fields, performance improvement cases due to surface deformation have been reported. Through these studies, we confirm the contribution of surface deformation techniques to the advancement of the bioengineering field. In the future, it is expected that the application of surface deformation techniques to the real-time interaction analysis between biological materials and dynamically deformable substrates will increase the utilization and importance of these techniques in various fields, including cell research and biosensors.
... The advantages of the use of fibrin as a scaffold in order to promote the repair of chondral tissue (adapted from reference[50]). ...
Biomaterials are mostly any natural and synthetic materials which are compatible from a biological point of view with the human body. Biomaterials are widely used to sustain, increase, reestablish or substitute the biological function of any injured tissue and organ from the human body. Additionally, biomaterials are uninterruptedly in contact with the human body, i.e., tissue, blood and biological fluids. For this reason, an essential feature of biomaterials is their biocompatibility. Consequently, this review summarizes the classification of different types of biomaterials based on their origin, as natural and synthetic ones. Moreover, the advanced applications in pharmaceutical and medical domains are highlighted based on the specific mechanical and physical properties of biomaterials, concerning their use. The high-priority challenges in the field of biomaterials are also discussed, especially those regarding the transfer and implementation of valuable scientific results in medical practice.
