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Fibrous proteins of the extracellular matrix. a The basic unit of collagen fibrils is the tropocollagen triple-helix comprised of three α-chains. Each α-chain forms a helix where glycine is positioned at every third amino acid, often with glycine-proline-X or glycine-Xhydroxyproline repeats. Tropocollagen molecules form collagen fibrils by binding together in a quarter-stagger pattern that gives collagen its characteristic banding pattern. Collagen fibrils vary in diameter, alignment, and packing depending on the tissue they are found in. b Fibronectin (FN) polypeptide chains are comprised of three variable domains: FNI, FNII, and FNIII. Each polypeptide chain contains 12 FNI domains, 2 FNII domains, and 15-17 FNIII domains. Pre-mRNA splicing produces at least 20 variants of the protein in humans. Fibronectin polypeptide chains form a 'V' shape at the C-terminus via two disulfide bonds. Fibronectin is secreted as a globular protein that is stretched by cells into its fibrillar form. c Tenascin fibrils are comprised of varying numbers of heptad repeats, epidermal growth factor (EGF)-like repeats, fibronectin type III (FNIII) domains, and a globular fibrinogen domain capping the C-terminus. Tenascin fibrils bind at the N-terminus to form hexamers and trimers. d Tropoelastin molecules contain alternating hydrophobic domains and crosslinking domains. Elastin fibers are generally relaxed and coiled. Lysyl-oxidase crosslinks the fibers together to form a network. When the tissue is stressed, the elastin uncoils and elongates. e Each laminin contains an α-chain, a β-chain, and a γ-chain. There are five α-chain, four β-chain, and three γ-chain variants. Each chain contains a combination of laminin N-terminal domains, laminin IV type A domains, laminin IV type B domains, and EGF-like repeats. α-chains contain laminin G-like domains at the C-terminal of the peptide. Laminins form helical glycoproteins composed of three polypeptide chains (α, β, γ). There are 15 known combinations of α-, β-, and γ-chains. Three short chains (α, β, γ) at the N-terminal interact with the ECM, and a long chain (α) at the C-terminal binds to cell-membrane integrins. Laminin 111 shown
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Tissue engineering often uses synthetic scaffolds to direct cell responses during engineered tissue development. Since cells reside within specific niches of the extracellular matrix, it is important to understand how the matrix guides cell response and then incorporate this knowledge into scaffold design. The goal of this review is to review eleme...
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... the largest of the collagen fibers align perpendicular to the surface. Type I collagen fibers also support the myofibrils in muscle 13 and are a major component of bone and blood vessels, forming a concentric weave pattern. 14 Despite the abundance of collagen in the body, substantial gaps remain in understanding its interactions with cells. 15 ( Fig. 1 and Table ...
Citations
... A bionic scaffold with appropriate porosity serves as a replacement for the cytoskeleton in the initial phases of bone healing. In comparison to a low-porosity environment, cells cultured in porous scaffolds exhibited an elongated spindle-like morphology and more efficient migration [ 93 ]. In another aspect, tendon repair also requires specific 3D geometry to guide the elongated deposition of collagen. ...
Tendon/ligament–bone junctions (T/LBJs) are susceptible to damage during exercise, resulting in anterior cruciate ligament rupture or rotator cuff tear; however, their intricate hierarchical structure hinders self-regeneration. Multiphasic strategies have been explored to fuel heterogeneous tissue regeneration and integration. This review summarizes current multiphasic approaches for rejuvenating functional gradients in T/LBJ healing. Synthetic, natural, and organism-derived materials are available for in vivo validation. Both discrete and gradient layouts serve as sources of inspiration for organizing specific cues, based on the theories of biomaterial topology, biochemistry, mechanobiology, and in situ delivery therapy, which form interconnected network within the design. Novel engineering can be constructed by electrospinning, 3-dimensional printing, bioprinting, textiling, and other techniques. Despite these efforts being limited at present stage, multiphasic scaffolds show great potential for precise reproduction of native T/LBJs and offer promising solutions for clinical dilemmas.
... Synthetic scaffolds may lack some of the intrinsic biochemical cues found in natural extra-cellular matrices, necessitating the incorporation of biologically active molecules to achieve optimal performance. 6 Among the different types of biodegradable synthetic polyesters, polycaprolactone (PCL) has been widely used in medical studies, especially in the field of wound healing and tissue engineering. 7 The products of its enzymatic breakdown are easily metabolized and excreted by the body. ...
Scaffolds play a crucial role in tendon healing by providing structural support, promoting cell infiltration, and guiding tissue regeneration. Polycaprolactone (PCL) has been used as a polymer in biological scaffolds for several tissue engineering studies. This study aimed to investigate the effects of curcumin-loaded PCL scaffold on Achilles tendon using a tenotomy model in rats. Twenty adult male Wistar rats were randomized into two groups. In control group, tenotomy and suture placement were performed. The identical intervention followed by the implantation of curcumin-loaded PCL scaffold around the tendon stumps was performed in the treatment group. The nanofibrous PCL scaffold containing 5.00% curcumin was fabricated by electrospinning. Walking track analysis was performed weekly. Then, after 6 weeks, histopathological examination and tendon mechanical tests were performed. The weekly walking track analysis revealed a significant improvement in Achilles functional index in scaffold-treated rats from week three to six. The rate of functional improvement was remarkably slower in the control group. Histopathological examination revealed aseptic inflammation and enhanced neovascularization in the treatment group. Also, collagen arrangement and density were significantly improved in this group compared to the control samples including less regular orientation and loose organization of collagen fibers. Significant increase in mechanical properties, except for strain, was observed in the treatment group. The present study demonstrated that implantation of curcumin-loaded PCL scaffold resulted in increased fibrillar architecture, as well as improved mechanical properties and Achilles functional index in rats. To reduce the biodegradation-induced inflammation, an anti-inflammatory treatment is recommended.
... These findings are consistent with previous studies where hydrophobic surfaces promote migration of vascular endothelial cells and corneal cells by increasing the expression of Rho GTPases, which facilitate migration. 30 Whereas surfaces with hydrophilic properties promote cell adhesion and stronger adhesion corresponds with slower cell migration. 31,32 On the TiOx surface, a water contact angle of 74 ○ corresponded to the strongest fibroblast adhesion and the slowest migration speed. ...
The extracellular matrix provides a structural foundation for cells while also providing biophysical and biochemical signals that guide and influence cell migration. Previous studies have demonstrated that factors such as topography, material composition, and surface energy can significantly influence the migratory behaviors of cells. However, the relationship between surface energy and cell migration on various surfaces is not well understood. To investigate this, we fabricated polydimethylsiloxane (PDMS) platforms featuring nanopillars, as well as silicon oxide (SiOx) and titanium oxide (TiOx) surface coatings. The study examined the cells’ migration speed, morphology, and spreading in relation to the different surface properties and surface energies. Cells exhibited distinctive migration behaviors on the PDMS platforms with nanopillars and various surface coatings. In contrast to the flat PDMS, cells cultured on the SiOx and TiOx coatings exhibited less elongated morphologies, decreased mobility, and larger overall cell areas. Specifically, cells had the smallest cell elongation on the SiOx surface and the lowest migration speed on platforms coated with TiOx. In contrast, cells cultured on the nanopillar surface exhibited increased migration speeds, more elongated morphologies, and smaller overall cell areas. These findings suggest that cell migration behavior is obviously affected by the existence of nanopillars or the type of surface coating, which in turn is relevant to the surface energy of the platform. Elucidating the relationships between various surface properties, resulting cell migration behaviors, and overall surface energy could enable improved control over cell migration in a bionic platform designed to promote tissue regeneration and repair.
... Additionally, our results demonstrated that nanofibrous scaffolds spun at higher RPMs had significantly greater stiffness than those spun at lower RPMs. This observation coincides with literature, as the alignment of the fibers affects stiffness, with the highest stiffness occurring when fibers are perfectly aligned [60]. The literature also indicates that lower-diameter fibers increase their crystallinity and molecular orientation, leading to enhanced mechanical strength and stiffness [61]. ...
Tendons enable movement through their highly aligned extracellular matrix (ECM), predominantly composed of collagen I. Tendinopathies disrupt the structural integrity of tendons by causing fragmentation of collagen fibers, disorganization of fiber bundles, and an increase in glycosaminoglycans and microvasculature, thereby driving the apparent biomechanical and regenerative capacity in patients. Moreover, the complex cellular communication within the tendon microenvironment ultimately dictates the fate between healthy and diseased tendon, wherein extracellular vesicles (EVs) may facilitate the tendon’s fate by transporting biomolecules within the tissue. In this study, we aimed to elucidate how the EV functionality is altered in the context of tendon microenvironments by using polycaprolactone (PCL) electrospun scaffolds mimicking healthy and pathological tendon matrices. Scaffolds were characterized for fiber alignment, mechanical properties, and cellular activity. EVs were isolated and analyzed for concentration, heterogeneity, and protein content. Our results show that our mimicked healthy tendon led to an increase in EV secretion and baseline metabolic activity over the mimicked diseased tendon, where reduced EV secretion and a significant increase in metabolic activity over 5 days were observed. These findings suggest that scaffold mechanics may influence EV functionality, offering insights into tendon homeostasis. Future research should further investigate how EV cargo affects the tendon’s microenvironment.
... Scaffolding biomaterials appear early in tissue engineering, they provide a structural framework that resembles the fibrous protein component of the extracellular matrix (ECM) (Jenkins and Little 2019). ...
The rapid progress in cultivated meat research has engendered considerable attention towards the edible scaffolding biomaterials employed in the production. Cellulose has the advantages in availability, edibility, animal-free origin, etc., which show its potential in wide fields. This review begins by presenting the fundamental physical and chemical properties of cellulose from different sources, including plant and bacterial cellulose. Subsequently, we summarize the application of cellulose especially in cultivated meat and tissue engineering. Furthermore, we explore various methods for preparing cellulose-based scaffolds for cultivated meat, encompassing five specific structural variations. In the end, associated with utilizing cellulose in cultivated meat production, we address several primary challenges surrounding to cell adhesion, scaling up, processibility and mechanical properties, and provide potential innovations. This review underscores the potential of cellulose as a versatile biomaterial in the cultivated meat industry and provides insight into addressing critical challenges for its integration.
... So biomimetic scaffold is developed, biomimetic scaffold is synthetic scaffolds which is engineered to mimic key structural and functional features of the natural extracellular matrix for a better and more effective way to support cell regeneration. The synthetic biomimetic scaffolds are usually made by biodegradable polymers such as PLA [8]. ...
Cartilage injury is considered the major cause of joint pain, swelling and dysfunction. Due to the cartilage tissue’s limited repair capacity, it’s very urgent and crucial to develop and investigate biomaterials to improve effective cartilage regeneration. Over the past decade, researchers focused of the design and preparation of a variety of synthetic materials. There synthetic scaffolds are expected to provide a favorable cellular microenvironment which is beneficial for cartilage regeneration. This review comprehensively reviews the major synthetic materials that have been recently applied in cartilage regeneration engineering, including a variety of polymers and a number of 3D printed materials. These materials have unique physicochemical structures and properties that can provide biocompatible three-dimensional porous structures, mimic the extracellular matrix environment in vivo, and promotes cell adhesion, proliferation, and differentiation. These properties all guide the orderly regeneration of cartilage tissues. Especially through the composite with bioactive molecules, nanomaterials, etc., these materials can also realize the controlled release of biological signals and precisely regulate cell behavior. In addition, by compositing natural polymers with synthetic polymers gives the hybrid scaffolds good bioactivity, it will also enhance their mechanical properties as well as the scaffold elasticity. These techniques allow researchers to develop the most ideal scaffold that perfectly mimics the natural cartilage environment.
... Additionally, the surface roughness of implants influences osseointegration. Research by Boyan et al. indicated an inverse relationship between the viability of cells on a material's surface and its roughness [105], with rougher surfaces fostering in vivo bone formation and smoother surfaces predisposing to fibrous interfaces [106,107]. It has also been reported that rough surfaces induce inflammatory cytokine expression and are prone to degradation byproducts that attract inflammatory cells and generate ROS [108]. ...
Diabetes mellitus, characterized by enduring hyperglycemia, precipitates oxidative stress, engendering a spectrum of complications, notably increased bone vulnerability. The genesis of reactive oxygen species (ROS), a byproduct of oxygen metabolism, instigates oxidative detriment and impairs bone metabolism in diabetic conditions. This review delves into the mechanisms of ROS generation and its impact on bone homeostasis within the context of diabetes. Furthermore, the review summarizes the cutting-edge progress in the development of ROS-neutralizing biomaterials tailored for the amelioration of diabetic osteopathy. These biomaterials are engineered to modulate ROS dynamics, thereby mitigating inflammatory responses and facilitating bone repair. Additionally, the challenges and therapeutic prospects of ROS-targeted biomaterials in clinical application of diabetic bone disease treatment is addressed.
... Additionally, there were significant changes in width and angle of collagen fibers of MED dECM depleted of EMILIN1. Cellular behavior is known to vary depending on the alignment of matrisome fibers, so these observed alterations in fiber architecture suggest changes in the structure of the depleted hydrogel despite depletion in protein abundance not reaching statistical significance [58][59][60][61][62]. Further studies to determine downstream effects of these changes on cellular behavior will be needed to explore functionality of the observed phenotype. ...
While ovarian tissue cryopreservation (OTC) is an important fertility preservation option, it has its limitations. Improving OTC and ovarian tissue transplantation (OTT) must include extending the function of reimplanted tissue by reducing the extensive activation of primordial follicles (PMFs) and eliminating the risk of reimplanting malignant cells. To develop a more effective OTT, we must understand the effects of the ovarian microenvironment on folliculogenesis. Here, we describe a method for producing decellularized extracellular matrix (dECM) hydrogels that reflect the protein composition of the ovary. These ovarian dECM hydrogels were engineered to assess the effects of ECM on in vitro follicle growth, and we developed a novel method for selectively removing proteins of interest from dECM hydrogels. Finally, we validated the depletion of these proteins and successfully cultured murine follicles encapsulated in the compartment-specific ovarian dECM hydrogels and these same hydrogels depleted of EMILIN1. These are the first, optically clear, tailored tissue-specific hydrogels that support follicle survival and growth comparable to the “gold standard” alginate hydrogels. Furthermore, depleted hydrogels can serve as a novel tool for many tissue types to evaluate the impact of specific ECM proteins on cellular and molecular behavior.
... 17 Porosity also increases surface area, which may be beneficial for cellular migration and attachment. 16,18,19 Therefore, FT-DPM's enhanced porosity may increase its capacity as a biocompatible scaffold for nutrient exchange, cell migration, and neovascularization, which is further supported by host cell infiltration, neovascularization, and evidence of tissue remodelling observed presently with FT-DPM in vivo. ...
Allografts derived from live‐birth tissue obtained with donor consent have emerged as an important treatment option for wound and soft tissue repairs. Placental membrane derived from the amniotic sac consists of the amnion and chorion, the latter of which contains the trophoblast layer. For ease of cleaning and processing, these layers are often separated with or without re‐lamination and the trophoblast layer is typically discarded, both of which can negatively affect the abundance of native biological factors and make the grafts difficult to handle. Thus, a full‐thickness placental membrane that includes a fully‐intact decellularized trophoblast layer was developed for homologous clinical use as a protective barrier and scaffold in soft tissue repairs. Here, we demonstrate that this full‐thickness placental membrane is effectively decellularized while retaining native extracellular matrix (ECM) scaffold and biological factors, including the full trophoblast layer. Following processing, it is porous, biocompatible, supports cell proliferation in vitro, and retains its biomechanical strength and the ability to pass through a cannula without visible evidence of movement or damage. Finally, it was accepted as a natural scaffold in vivo with evidence of host‐cell infiltration, angiogenesis, tissue remodelling, and structural layer retention for up to 10 weeks in a murine subcutaneous implant model.
... PVA-based nanofibrous scaffolds have demonstrated considerable promise in various tissue engineering applications, such as skin, bone, neural, vascular, corneal as well as vehicles for controlled drug deliveries [4]. However, being a synthetic polymer, PVA lacks cell signaling cues which can be superseded by the incorporation of natural polymer [5]. Elastin (EL) is a naturally occurring extracellular protein commonly found in the lung, artery, skin, bladder, elastic ligament and cartilage [6]. ...
Electrospinning technique is widely used to fabricate nanofibrous membranes mimicking the extracellular matrix structure. The utilization of synthetic polyvinyl alcohol (PVA) as the base material to construct electrospun nanofibers is often related to the limitation of biological function. Therefore, in this study, elastin (EL), a natural polymer, was incorporated into PVA matrix to overcome the biofunctional limitation. The ideal electrospinning parameters for the fabrication of PVA/EL electrospun nanofibers were investigated by varying the compositions of PVA/EL at 9.9/0.1, 9.5/0.5 and 9.0/1.0 (v/v) and the applied voltages at 18, 20 and 22 kV. With the increasing voltage from 18 to 22 kV, the mean fiber diameter decreased for the PVA and PVA/EL of 9.9/0.1 (v/v) while a fluctuating trend was observed for the 9.5/0.5 and 9.0/1.0 (v/v). The homogenous nanofibers construction with no beads was observed in the PVA/EL 9.5/0.5 (v/v). Both PVA and PVA/EL nanofibrous membranes displayed hydrophilicity with water contact angles below than 90°. In conclusion, the PVA/EL 9.5/0.5 (v/v) fabricated at 20 kV, possessed the ideal fiber morphology and wettability, to be subjected for biomedical applications.
