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Schematic of the fabrication strategy for layered collagen elastin hybrids. Collagen gels were cast at 4 mm thickness. (A) Collagen lamellae were dried to a dry thickness of approximately 35 µm, (B) and layered into multi-layer collagen mats and ablated. (C) Multi-layer lamellae were embedded with elastin (blue) into a multi-layer hybrid.
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Noting the abundance and importance of collagen as a biomaterial, we have developed a facile method for the production of a dense fibrillar extracellular matrix mimicking collagen-elastin hybrids with tunable mechanical properties. Through the use of excimer-laser technology, we have optimized conditions for the ablation of collagen lamellae withou...
Citations
... In biomimetic composites, the influence of FVF on soft synthetic composites have been investigated, mainly for tissue engineering applications (Caves et al., 2010a(Caves et al., , 2010c(Caves et al., , 2011Kumar et al., 2013aKumar et al., , 2013bKumar et al., , 2014Naik et al., 2014;Ayala et al., 2015;Sharabi et al., 2019Sharabi et al., , 2015Sharabi et al., , 2016 and found to affect different mechanical properties such as strength, stiffness, and ultimate strains. ...
... Crimped fibers were synthetically fabricated as a part of a laminate or as isolated fibers to investigate their deformation behavior (Caves et al., 2010c;Fleischer et al., 2013;Nunes et al., 2013;Chen et al., 2014;Kumar et al., 2014;Naik et al., 2014;Pen-hsiu Grace et al., 2014;Szczesny et al., 2016;Wu et al., 2017;Sharabi and Wagner, 2021). They were also beneficial for embedded cells and altered strain transmission to cells (Fleischer et al., 2013;Szczesny et al., 2016). ...
Through years of evolution, biological soft fibrous tissues have developed remarkable functional properties, unique hierarchical architectures, and -most notably, an unparalleled and extremely efficient deformation ability. Whereas the structure-function relationship is well-studied in natural hard materials, soft materials are not getting similar attention, despite their high prevalence in nature. These soft materials are usually constructed as fiber-reinforced composites consisting of diverse structural motifs that result in an overall unique mechanical behavior with large deformations. Biomimetics of their mechanical behavior is currently a significant bioengineering challenge. The unique properties of soft fibrous tissues stem from their structural complexity, which, unfortunately, also hinders our ability to generate adequate synthetic analogs, such that autografts remain the “gold standard” materials for soft-tissue repair and replacement. This review seeks to understand the structural and deformation mechanisms of soft collagenous tissues, with a particular emphasis on tendon and ligaments, the annulus fibrosus (AF) in the intervertebral disc (IVD), skin, and blood vessels. We examined and compared different mechanical and structural motifs in these different tissue types, which are subjected to complex and varied mechanical loads, to isolate the mechanisms of their deformation behavior. Herein, we focused on their composite structure from a perspective of the different building blocks, architecture, crimping patterns, fiber orientation, organization and their structure-function relationship. In the second part of the review, we presented engineered soft composite applications that used these structural motifs to mimic the structural and mechanical behavior of soft fibrous tissues. Moreover, we demonstrated new methodologies and materials that use biomimetic principles as a guide. These novel architectural materials have tailor-designed J-shaped large deformations behavior. Structural motifs in soft composites hold valuable insights that could be exploited to generate the next generation of materials. They actually have a two-fold effect: 1) to get a better understanding of the complex structure-function relationship in a simple material system using reverse biomimetics and 2) to develop new and efficient materials. These materials could revolutionize the future tailor-designed soft composite materials together with various soft-tissue repair and replacement applications that will be mechanically biocompatible with the full range of native tissue behaviors.
https://www.frontiersin.org/articles/10.3389/fmats.2021.793647/full
... They photo-crosslinked methacrylated gelatin gels using crosslinker (lithium phenyl-2,4,6-trimethylbenzoylphosphinate) with hyaluronan to make the hydrogels. They used the hydrogel to examine the cell viability and adipose [145] Excimer-laser ablation Skin tissue Collagen gel [146] Molding technique Vascular tissue Collagen/alginate/fibrin [120] Solution polymerization Soft tissue Collagen/silk fibroin [147] Cross-linking Corneal tissue disintegration of ASCs for up to 30 days and observed satisfactory cell viability within 24 h. They found mature adipocytes due to adipogenic differentiation of ASCs and increased significantly until 28 days of culture. ...
Recently, the advantages of biopolymers over conventional plastic polymers are unprecedented, provided that they are used in situations in which they raise the functionality and generate extra benefits for human life. Therefore, biopolymers have received much attention because they play an important place in day-to-day life for their specific tunable characteristics, making them attractive in a wide range of applications. Biopolymers can produce materials with tunable properties such as biodegradability, biocompatibility, renewability, inexpensiveness, availability, which are critically important for designing materials for use in biomedical applications. In addition to these properties, smart biopolymers could be prepared by changing the polymer components, which would create more target oriented applications. Therefore, this review interprets how biopolymers and their various forms can be potentially used in biomedical applications, including drug delivery, infections, tissue engineering, wound healings, and other as wells. Special emphasis will be provided on the applications of biopolymers in the field of drug delivery, tissue engineering, infections, and wound healing, which indicate the advancement and employment of the various biopolymers in recent biomedical applications.
Graphical abstract
... Such movement, and the consequential redistribution of the gel network, requires and additional work, which causes an increment in the opposition to deformation. This higher resistance capacity can help to produce stability, which is an essential factor to the field of soft tissue engineering applications [63]. ...
Hydrogels exhibit excellent properties that enable them as nanostructured scaffolds for soft tissue engineering. However, single-component hydrogels have significant limitations due to the low versatility of the single component. To achieve this goal, we have designed and characterized different multi-component hydrogels composed of gelatin, alginate, hydroxyapatite, and a protein (BSA and fibrinogen). First, we describe the surface morphology of the samples and the main characteristics of the physiological interplay by using fourier transform infrared (FT-IR), and confocal Raman microscopy. Then, their degradation and swelling were studied and mechanical properties were determined by rheology measurements. Experimental data were carefully collected and quantitatively analyzed by developing specific approaches and different theoretical models to determining the most important parameters. Finally, we determine how the nanoscale of the system influences its macroscopic properties and characterize the extent to which degree each component maintains its own functionality, demonstrating that with the optimal components, in the right proportion, multifunctional hydrogels can be developed.
... Similarly, other studies have demonstrated that fibrous hybrid structures with tunable mechanical properties can be obtained by mixing nonrecombinant collagen with ELRs, being of great interest for their application in TERM or drug delivery [123]. In this regard, complex hybrid systems that closely mimic ECM composition, structure and architecture were obtained using different techniques of fabrication such as microtransfer molding or microablation [139,140]. ...
Elastin-like recombinamers (ELRs), which derive from one of the repetitive domains found in natural elastin, have been intensively studied in the last few years from several points of view. In this mini review, we discuss all the recent works related to the investigation of ELRs, starting with those that define these polypeptides as model intrinsically disordered proteins or regions (IDPs or IDRs) and its relevance for some biomedical applications. Furthermore, we summarize the current knowledge on the development of drug, vaccine and gene delivery systems based on ELRs, while also emphasizing the use of ELR-based hydrogels in tissue engineering and regenerative medicine (TERM). Finally, we show different studies that explore applications in other fields, and several examples that describe biomaterial blends in which ELRs have a key role. This review aims to give an overview of the recent advances regarding ELRs and to encourage further investigation of their properties and applications.
... For example, the geometry/topography of ECM has impacts on cell attachments. In turn, the focal-adhesion structure modulates the internal cytoskeleton to change cell shape and subsequently biological processes by the mechanotransduction process (Kumar et al., 2014). Many studies have developed biomimetic matrixes to demonstrate how ECM modulates cellular behaviors through physical or chemical cues (Causa, Netti, & Ambrosio, 2007). ...
Microenvironmental factors including physical and chemical cues can regulate stem cells as well as terminally differentiated cells to modulate their biological function and differentiation. However, one of the physical cues, the substrate's dimensionality, has not been studied extensively. In this study, the flow‐focusing method with a microfluidic device was used to generate gelatin bubbles to fabricate highly ordered three‐dimensional (3D) scaffolds. Rat H9c2 myoblasts were seeded into the 3D gelatin bubble‐based scaffolds and compared to those grown on 2D gelatin‐coating substrates to demonstrate the influences of spatial cues on cell behaviors. Relative to cells on the 2D substrates, the H9c2 myoblasts were featured by a good survival and normal mitochondrial activity but slower cell proliferation within the 3D scaffolds. The cortical actin filaments of H9c2 cells were localized close to the cell membrane when cultured on the 2D substrates, while the F‐actins distributed uniformly and occupied most of the cell cytoplasm within the 3D scaffolds. H9c2 myoblasts fused as multinuclear myotubes within the 3D scaffolds without any induction but cells cultured on the 2D substrates had a relatively lower fusion index even differentiation medium was provided. Although there was no difference in actin α 1 and myosin heavy chain 1, H9c2 cells had a higher myogenin messenger RNA level in the 3D scaffolds than those of on the 2D substrates. This study reveals that the dimensionality influences differentiation and fusion of myoblasts.
... Micro-transfer-molding has been demonstrated as an appropriate bottom-up approach to fabricate various microstructures from natural materials 28,29 , and to integrate these materials with microelectronic devices 30 . In addition, excimer laser micromachining has been used as an effective top-down rapid production technique to produce microstructures in natural materials 31 . Bringing together these technologies to bear on natural products such as ECM materials, we created implantable ECMmicroelectrodes integrated with insertion stents at high throughput, while preserving the biological nature of these materials. ...
Intracortical neural microelectrodes, which can directly interface with local neural microcircuits with high spatial and temporal resolution, are critical for neuroscience research, emerging clinical applications, and brain computer interfaces (BCI). However, clinical applications of these devices remain limited mostly by their inability to mitigate inflammatory reactions and support dense neuronal survival at their interfaces. Herein we report the development of microelectrodes primarily composed of extracellular matrix (ECM) proteins, which act as a bio-compatible and an electrochemical interface between the microelectrodes and physiological solution. These ECM-microelectrodes are batch fabricated using a novel combination of micro-transfer-molding and excimer laser micromachining to exhibit final dimensions comparable to those of commercial silicon-based microelectrodes. These are further integrated with a removable insertion stent which aids in intracortical implantation. Results from electrochemical models and in vivo recordings from the rat’s cortex indicate that ECM encapsulations have no significant effect on the electrochemical impedance characteristics of ECM-microelectrodes at neurologically relevant frequencies. ECM-microelectrodes are found to support a dense layer of neuronal somata and neurites on the electrode surface with high neuronal viability and exhibited markedly diminished neuroinflammation and glial scarring in early chronic experiments in rats.
... To deposit ECM films on the distal end of the arrays, randomly selected Au-parylene devices are lifted-off from the silicon carrier and placed in a polydimethylsiloxane (PDMS) mold, where a collagen or collagen-fibronectin precursor solution is casted and polymerized in a controlled humidity and temperature environment. After polymerization, the final layout of the device is precisely defined by ablating the excess protein film via UV excimer laser micromachining, which excites and dissociates the molecular bonds while preventing excessive heating and decomposition to elemental compounds that would result in protein denaturation [51]. Imaging of the device cross section after UV ablation (Fig 1D) confirms the integrity of the protein structure and shows that more than 60% of the implanted area of the arrays is composed of natural material, with the ECM film forming a 20 μm thick layer completely encapsulating the Au-parylene synthetic interface. ...
Intracranial electrodes are a vital component of implantable neurodevices, both for acute diagnostics and chronic treatment with open and closed-loop neuromodulation. Their performance is hampered by acute implantation trauma and chronic inflammation in response to implanted materials and mechanical mismatch between stiff synthetic electrodes and pulsating, natural soft host neural tissue. Flexible electronics based on thin polymer films patterned with microscale conductive features can help alleviate the mechanically induced trauma; however, this strategy alone does not mitigate inflammation at the device-tissue interface. In this study, we propose a biomimetic approach that integrates microscale extracellular matrix (ECM) coatings on microfabricated flexible subdural microelectrodes. Taking advantage of a high-throughput process employing micro-transfer molding and excimer laser micromachining, we fabricate multi-channel subdural microelectrodes primarily composed of ECM protein material and demonstrate that the electrochemical and mechanical properties match those of standard, uncoated controls. In vivo ECoG recordings in rodent brain confirm that the ECM microelectrode coatings and the protein interface do not alter signal fidelity. Astrogliotic, foreign body reaction to ECM coated devices is reduced, compared to uncoated controls, at 7 and 30 days, after subdural implantation in rat somatosensory cortex. We propose microfabricated, flexible, biomimetic electrodes as a new strategy to reduce inflammation at the device-tissue interface and improve the long-term stability of implantable subdural electrodes.
... With increasing amounts of ADA, the maximum compliance J value at the 50 s decreases from 56.351 Pa − 1 to 2.102 Pa − 1 and increases from 2.651% to 28.217% in the R ex value, illustrating that the ability of the resistance to deformation and the elastic response of the cross-linked collagen solution reinforces due to the entanglement of collagen chains by ADA crosslinking. The higher resistance ability to deformation and recoverable strain could contribute to production stability, which is dramatically potential to applications in the fields of soft tissue manufacturing that requires the higher ability to resist stress [40]. ...
The elaboration of the rheological behaviors of alginate dialdehyde (ADA) crosslinked collagen solutions, along with the quantitative analysis via numerical models contribute to the controllable design of ADA crosslinked solution system's fluid mechanics performance during manufacturing process for collagen biomaterials. In the present work, steady shear flow, dynamical viscoelasticity, creep-recovery, thixotropy tests were performed to characterize the rheological behaviors of the collagen solutions incorporating of ADA from the different aspects and fitted with corresponding numerical models. It was found that pseudoplastic properties of all samples enhanced with increasing amounts of ADA, which was confirmed by the parameters calculated from the Ostwald-de Waele model, Carreau and Cross model, for instance, the non-Newtonian index (n) decreased from 0.786 to 0.201 and a great increase by 280 times in value of viscosity index (K) was obtained from Ostwald-de Waele model. The forth-mode Leonov model was selected to fit all dynamic modulus-frequency curves due to its higher fitting precision (R² > 0.99). It could be found that the values of correlation shear viscosity (ηk) increased and the values of relaxation time (θk) decreased with increasing ADA at the fixed k value, suggesting that the incorporation of ADA accelerated the transformation of the collagen solutions from liquid-like to gel-like state due to more formation of CN linkages between aldehyde groups and lysine residues. Also, the curves of creep and recovery phase of the native and crosslinked collagen solutions were simulated well using Burger model and a semi-empirical model, respectively. The ability to resist to deformation and elasticity strengthened for the samples with higher amounts of ADA, accompanied with the important fact that compliance value (J50) decreased from 56.317 Pa− 1 to 2.135 Pa− 1 and the recovery percentage (Rcreep) increased from 2.651% to 28.217%. Finally, it was found that the area of thixotropic loop increased from 8.942 Pa/s to 17.823 Pa/s with increasing introduction of ADA, suggesting that stronger thixotropic behavior was associated with higher amount of ADA. Furthermore, Herschel–Bulkley model was employed to describe the up and down curves of all samples and it was confirmed that all collagen solutions belonged to pseudoplastic fluid (the flow index < 1) without apparent yield stress and shear-thinning behaviors were more obvious with increasing additions of ADA according to the increasing consistency coefficient K values. Overall, this work contributed a new insight into the interactions between collagen and ADA based on quantitative rheological methods reflecting the different rheological properties and the results obtained should be of great utility in the extensive application of ADA crosslinked collagen solutions into diverse collagen-based materials.
... For example, excimer-laser technology was used for the ablation of collagen lamellae that were subsequently embedded with recombinant elastin to generate collagen-elastin hybrids. These hybrids were suitable as synthetic extracellular matrices that provided mechanical strength and promoted material-cell interactions [27]. Similarly, synthetic collagen fibers were arranged into parallel arrays, embedded within a thin membrane of a recombinant elastin, and rolled into multi-layered tubes for vascular tissue engineering [28]. ...
... 25 The reader is directed to the following reviews for more details. 29,[149][150][151] These synthetic elastin matrices, oftentimes combined with synthetic collagen matrices, have been used to recapitulate features of the ECM in applications for tissue repair, [152][153][154][155][156] drug delivery, 29,157,158 and materials with tunable material properties. 150,154,[159][160][161] Conclusion Bottom-up engineering of peptide-based supramolecular structures has allowed biomimicry at multiple length scales, including nanofibrous morphologies that mimic native ECM. ...
... 29,[149][150][151] These synthetic elastin matrices, oftentimes combined with synthetic collagen matrices, have been used to recapitulate features of the ECM in applications for tissue repair, [152][153][154][155][156] drug delivery, 29,157,158 and materials with tunable material properties. 150,154,[159][160][161] Conclusion Bottom-up engineering of peptide-based supramolecular structures has allowed biomimicry at multiple length scales, including nanofibrous morphologies that mimic native ECM. Learning from natural self-assembly cues, bioinspired scientists can now generate a series of materials that can closely recapitulate higher order protein structure by tailoring primary and secondary composition to replace dependence on synthetic or animal derived matrices that may cause adverse host reactions. ...
Recent strides in the development of multifunctional synthetic biomimetic materials through the self-assembly of multi-domain peptides and proteins over the past decade have been realized. Such engineered systems have wide-ranging application in bioengineering and medicine. This review focuses on fundamental fiber forming α-helical coiled-coil peptides, peptide amphiphiles, and amyloid-based self-assembling peptides; followed by higher order collagen- and elastin-mimetic peptides with an emphasis on chemical / biological characterization and biomimicry.
