Elastic Scaffolds Research Articles

Effects of Elasticity on Cell Proliferation in a Tissue-Engineering Scaffold Pore

Scaffolds engineered for in vitro tissue engineering consist of multiple pores where cells can migrate along with nutrient-rich culture medium. The presence of the nutrient medium throughout the scaffold pores promotes cell proliferation, and this process depends on several factors such as scaffold geometry, nutrient medium flow rate, shear stress, cell-scaffold focal adhesions and elastic properties of the scaffold material. While numerous studies have addressed the first four factors, the mathematical approach described herein focuses on cell proliferation rate in elastic scaffolds, under constant flux of nutrients. As cells proliferate, the scaffold pores radius shrinks and thus, in order to sustain the nutrient flux, the inlet applied pressure on the upstream side of the scaffold pore must be increased. This results in expansion of the elastic scaffold pore, which in turn further increases the rate of cell proliferation. Considering the elasticity of the scaffold, the pore deformation allows further cellular growth beyond that of inelastic conditions. In this paper, our objectives are as follows: (i) Develop a mathematical model for describing fluid dynamics, scaffold elasticity and cell proliferation for scaffolds consist of identical nearly cylindrical pores; (ii) Solve the models and then simulate cellular proliferation within an elastic pore. The simulation can emulate real life tissue growth in a scaffold and offer a solution which reduces the numerical burdens. Lastly, our results demonstrated are in qualitative agreement with experimental observations reported in the literature.

A Unit Compound Structure Design: Poisson’s Ratio Is Autonomously Adjustable from Negative to Positive

The shape memory polymer (SMP) is a new type of smart material that can produce a shape memory effect through the stimulation of the external environment. In this article, the viscoelastic constitutive theory of the shape memory polymer and the mechanism of the bidirectional memory effect of the shape memory polymer are described. A chiral poly cellular circular concave auxetic structure based on a shape memory polymer made of epoxy resin is designed. Two structural parameters, α and β, are defined, and the change rule of Poisson's ratio under different structural parameters is verified by ABAQUS. Then, two elastic scaffolds are designed to assist a new type of cellular structure made of a shape memory polymer to autonomously adjust bidirectional memory under the stimulation of the external temperature, and two processes of bidirectional memory are simulated using ABAQUS. Finally, when a shape memory polymer structure implements the bidirectional deformation programming process, a conclusion is drawn that changing the ratio β of oblique ligament and ring radius has a better effect than changing the angle α of oblique ligament and horizontal in achieving the autonomously adjustable bidirectional memory effect of the composite structure. In summary, through the combination of the new cell and the bidirectional deformation principle, the autonomous bidirectional deformation of the new cell is achieved. The research can be used in reconfigurable structures, tuning symmetry, and chirality. The adjusted Poisson's ratio achieved by the stimulation of the external environment can be used in active acoustic metamaterials, deployable devices, and biomedical devices. Meanwhile, this work provides a very meaningful reference for the potential application value of metamaterials.

Elastic Fiber-Reinforced Silk Fibroin Scaffold with A Double-Crosslinking Network for Human Ear-Shaped Cartilage Regeneration

Elastic Fiber-Reinforced Silk Fibroin Scaffold with A Double-Crosslinking Network for Human Ear-Shaped Cartilage Regeneration

Upregulated desmin/integrin β1/MAPK axis promotes elastic cartilage regeneration with increased ECM mechanical strength.

Elastic cartilage tissue engineering is promising for providing available scaffolds for plastic reconstructive surgery. The insufficient mechanical strength of regenerative tissue and scarce resources of reparative cells are two obstacles for the preparation of tissue-engineered elastic cartilage scaffolds. Auricular chondrocytes are important reparative cells for elastic cartilage tissue engineering, but resources are scarce. Identifying auricular chondrocytes with enhanced capability of elastic cartilage formation is conducive to reducing the damage to donor sites by decreasing the demand on native tissue isolation. Based on the biochemical and biomechanical differences in native auricular cartilage, we found that auricular chondrocytes with upregulated desmin expressed more integrin β1, forming a stronger interaction with the substrate. Meanwhile, activated MAPK pathway was found in auricular chondrocytes highly expressing desmin. When desmin was knocked down, the chondrogenesis and mechanical sensitivity of chondrocytes were both impaired, and the MAPK pathway was downregulated. Finally, auricular chondrocytes highly expressing desmin regenerated more elastic cartilage with increased ECM mechanical strength. Therefore, desmin/integrin β1/MAPK signaling can not only serve as a selection standard but also a manipulation target of auricular chondrocytes to promote elastic cartilage regeneration.

Cyclic freeze–thaw grinding to decellularize meniscus for fabricating porous, elastic scaffolds

Decellularized meniscus extracellular matrix (dmECM)-based biological scaffolds in the forms of sponge, hydrogel, nanofiber, and composite have gained increasing interest in meniscus tissue engineering and regeneration. A common shortcoming of those scaffolds is insufficient mechanical strength and poor elasticity. Herein, we report a practicable protocol for milder meniscus decellularization to prepare elastic, porous dmECM scaffolds. Porcine meniscus was pulverized by cyclic freeze-thaw grinding and then treated with DNase to obtain fine dmECM particles. Individual dmECM particles were condensed to bulk preparation by centrifuge, followed by lyophilization to form blocks, and finally crosslinked by dehydrothermal treatment to obtain porous dmECM scaffolds. Our results show that the freeze-thaw grinding method was effective in removing cellular DNA with good retention of meniscus-derived bioactive components. The dmECM scaffold had porous structure with interconnected mesopores and good mechanical properties. Primary articular chondrocytes proliferated robustly and maintained chondrogenic characteristics and produce abundant collagen on dmECM scaffolds. Evaluation of biocompatibility in a rat model shows that the dmECM scaffold elicited minor foreign body reactions, indicating effective antigen removal from dmECM. This study provides an alternative for preparing dmECM and fabricating porous scaffolds for meniscus repair and regeneration.

Mathematical and Computational Modeling of Poroelastic Cell Scaffolds Used in the Design of an Implantable Bioartificial Pancreas

We present a multi-scale mathematical model and a novel numerical solver to study blood plasma flow and oxygen concentration in a prototype model of an implantable Bioartificial Pancreas (iBAP) that operates under arteriovenous pressure differential without the need for immunosuppressive therapy. The iBAP design consists of a poroelastic cell scaffold containing the healthy transplanted cells, encapsulated between two semi-permeable nano-pore size membranes to prevent the patient’s own immune cells from attacking the transplant. The device is connected to the patient’s vascular system via an anastomosis graft bringing oxygen and nutrients to the transplanted cells of which oxygen is the limiting factor for long-term viability. Mathematically, we propose a (nolinear) fluid–poroelastic structure interaction model to describe the flow of blood plasma through the scaffold containing the cells, and a set of (nonlinear) advection–reaction–diffusion equations defined on moving domains to study oxygen supply to the cells. These macro-scale models are solved using finite element method based solvers. One of the novelties of this work is the design of a novel second-order accurate fluid–poroelastic structure interaction solver, for which we prove that it is unconditionally stable. At the micro/nano-scale, Smoothed Particle Hydrodynamics (SPH) simulations are used to capture the micro/nano-structure (architecture) of cell scaffolds and obtain macro-scale parameters, such as hydraulic conductivity/permeability, from the micro-scale scaffold-specific architecture. To avoid expensive micro-scale simulations based on SPH simulations for every new scaffold architecture, we use Encoder–Decoder Convolution Neural Networks. Based on our numerical simulations, we propose improvements in the current prototype design. For example, we show that highly elastic scaffolds have a higher capacity for oxygen transfer, which is an important finding considering that scaffold elasticity can be controlled during their fabrication, and that elastic scaffolds improve cell viability. The mathematical and computational approaches developed in this work provide a benchmark tool for computational analysis of not only iBAP, but also, more generally, of cell encapsulation strategies used in the design of devices for cell therapy and bio-artificial organs.

Highly elastic and bioactive bone biomimetic scaffolds based on platelet lysate and biomineralized cellulose nanocrystals

Bone is a vascularized organic-inorganic composite tissue that shows a heavily-mineralized extracellular matrix (ECM) on the nanoscale. Herein, the nucleation of calcium phosphates during the biomineralization process was mimicked using negatively-charged cellulose nanocrystals (CNCs). These mineralized-CNCs were combined with platelet lysate to produce nanocomposite scaffolds through cryogelation to mimic bone ECM protein-mineral composite nature and take advantage of the bioactivity steaming from platelet-derived biomolecules. The nanocomposite scaffolds showed high microporosity (94–95%), high elasticity (recover from 75% strain cycles), injectability, and modulated platelet-derived growth factors sequestration and release. Furthermore, they increased alkaline phosphatase activity (up to 10-fold) and up-regulated the expression of bone-related markers (up to 2-fold), without osteogenic supplementation, demonstrating their osteoinductive properties. Also, the scaffolds promoted the chemotaxis of endothelial cells and enhanced the expression of endothelial markers, showing proangiogenic potential. These results suggest that the mineralized nanocomposite scaffolds can enhance bone regeneration by simultaneously promoting osteogenesis and angiogenesis.

Tuning gelatin–alginate bioink properties by introducing new decellularized elastic cartilage scaffolds for bioinspired composite membranes in orthopedics

Tuning gelatin–alginate bioink properties by introducing new decellularized elastic cartilage scaffolds for bioinspired composite membranes in orthopedics

Ultra‐robust stretchable electrode for e‐skin: In situ assembly using a nanofiber scaffold and liquid metal to mimic water‐to‐net interaction

AbstractThe development of stretchable electronics could enhance novel interface structures to solve the stretchability–conductivity dilemma, which remains a major challenge. Herein, we report a nano‐liquid metal (LM)‐based highly robust stretchable electrode (NHSE) with a self‐adaptable interface that mimics water‐to‐net interaction. Based on the in situ assembly of electrospun elastic nanofiber scaffolds and electrosprayed LM nanoparticles, the NHSE exhibits an extremely low sheet resistance of 52 mΩ sq−1. It is not only insensitive to a large degree of mechanical stretching (i.e., 350% electrical resistance change upon 570% elongation) but also immune to cyclic deformation (i.e., 5% electrical resistance increases after 330 000 stretching cycles with 100% elongation). These key properties are far superior to those of the state‐of‐the‐art reports. Its robustness and stability are verified under diverse circumstances, including long‐term exposure to air (420 days), cyclic submersion (30 000 times), and resilience against mechanical damages. The combination of conductivity, stretchability, and durability makes the NHSE a promising conductor/electrode solution for flexible/stretchable electronics for applications such as wearable on‐body physiological signal detection, human–machine interaction, and heating e‐skin. image

Biomimetic, highly elastic conductive and hemostatic gelatin/rGO-based nanocomposite cryogel to improve 3D myogenic differentiation and guide in vivo skeletal muscle regeneration

The conductive and hemostatic cryogel capable of mimicking skeletal muscle's conductivity and extracellular matrix component presents huge potential for in situ skeletal muscle tissue engineering. Herein, elastic and conductive nanocomposite cryogels were synthesized using amide bond crosslinked gelatin and poly(tannic acid) reduced graphene oxide (rGO@PTA) via cryopolymerization. The cryogels possessed excellent elasticity, blood-trigged shape memory and 3D macroporous structure. The incorporation of rGO@PTA enhanced the mechanical property and conductivity of the cryogel, and endowed the cryogels with anti-oxidation, and without disturbing the elasticity and macroporous structure. Besides, the rGO@PTA improved the fast degradation of gelatin cryogel to prolong its service life. The cell proliferation and myogenic differentiation of C2C12 myoblasts during 3D culture were significantly improved by the conductive cryogel scaffold. Especially, the cryogel with 4 mg/mL rGO@PTA presented the best cell proliferation and myogenic differentiation, and significantly improved the repair efficiency of volumetric muscle loss. Furthermore, it had better hemostatic efficiency than those of commercial gelatin sponge and gelatin cryogel. This study provides a new strategy to develop highly elastic, hemostatic and conductive scaffolds, which integrates hemostasis and tissue repair to promote skeletal muscle or other electrical signal responsive soft tissue repair via in situ tissue engineering approach.

Lignin reinforced hydrogels with fast self-recovery, multi-functionalities via calcium ion bridging for flexible smart sensing applications

Hydrogels have found applications in many different fields. However, poor mechanical properties, such as low elasticity and lack of rapid recovery under large deformation, can severely limit their applications. In this study, we developed lignin reinforced hydrogels made of calcium ion containing ternary polymers (lignosulfonate (LS), alginate (Alg), and polyacrylic acid (PAA)). The resultant hydrogel has excellent elasticity, rapid self-recovery, and multi-functionalities. The covalent PAA network acts as the elastic scaffold of hydrogel, while calcium bridging networks of LS, Alg, and PAA, as well as the strong hydrogen bonding network in the system, function as sacrifice bonds to dissipate energy and transfer stress. The PAA/LS/Alg/Ca hydrogels exhibit rapid and durable elastic recovery ability under large deformation with the highest compressive stress of 835 kPa (95% strain), highest tensile fracture stress of 357 kPa, and highest tensile strain of 1144%. In addition, these tough hydrogels show UV resistance, self-healing, antifreeze, and excellent electro-conductivity. When assembled into a strain sensor, stable and reliable electrical responses with 375 ms response time are demonstrated. The PAA/LS/Alg/Ca hydrogel strain sensors can monitor human movements with responsive and accurate physiological signals. These results support the conclusion that the PAA/LS/Alg/Ca hydrogel strain sensors have great application potential in flexible wearable electronics and smart devices.

Large full-thickness wounded skin regeneration using 3D-printed elastic scaffold with minimal functional unit of skin

Traditional tissue engineering skin are composed of living cells and natural or synthetic scaffold. Besize the time delay and the risk of contamination involved with cell culture, the lack of autologous cell source and the persistence of allogeneic cells in heterologous grafts have limited its application. This study shows a novel tissue engineering functional skin by carrying minimal functional unit of skin (MFUS) in 3D-printed polylactide-co-caprolactone (PLCL) scaffold and collagen gel (PLCL + Col + MFUS). MFUS is full-layer micro skin harvested from rat autologous tail skin. 3D-printed PLCL elastic scaffold has the similar mechanical properties with rat skin which provides a suitable environment for MFUS growing and enhances the skin wound healing. Four large full-thickness skin defects with 30 mm diameter of each wound are created in rat dorsal skin, and treated either with tissue engineering functional skin (PLCL + Col + MFUS), or with 3D-printed PLCL scaffold and collagen gel (PLCL + Col), or with micro skin islands only (Micro skin), or without treatment (Normal healing). The wound treated with PLCL + Col + MFUS heales much faster than the other three groups as evidenced by the fibroblasts migration from fascia to the gap between the MFUS dermis layer, and functional skin with hair follicles and sebaceous gland has been regenerated. The PLCL + Col treated wound heals faster than normal healing wound, but no skin appendages formed in PLCL + Col-treated wound. The wound treated with micro skin islands heals slower than the wounds treated either with tissue engineering skin (PLCL + Col + MFUS) or with PLCL + Col gel. Our results provide a new strategy to use autologous MFUS instead “seed cells” as the bio-resource of engineering skin for large full-thickness skin wound healing.

The Regeneration of Large-Sized and Vascularized Adipose Tissue Using a Tailored Elastic Scaffold and dECM Hydrogels.

A dome-shaped elastic poly(l-lactide-co-caprolactone) (PLCL) scaffold with a channel and pore structure was fabricated by a combinative method of 3D printing technology and the gel pressing method (13 mm in diameter and 6.5 mm in thickness) for patient-specific regeneration. The PLCL scaffold was combined with adipose decellularized extracellular matrix (adECM) and heart decellularized extracellular matrix (hdECM) hydrogels and human adipose-derived stem cells (hADSCs) to promote adipogenesis and angiogenesis. These scaffolds had mechanical properties similar to those of native adipose tissue for improved tissue regeneration. The results of the in vitro real-time PCR showed that the dECM hydrogel mixture induces adipogenesis. In addition, the in vivo study at 12 weeks demonstrated that the tissue-engineered PLCL scaffolds containing the hydrogel mixture (hdECM/adECM (80:20)) and hADSCs promoted angiogenesis and adipose tissue formation, and suppressed apoptosis. Therefore, we expect that our constructs will be clinically applicable as material for the regeneration of patient-specific large-sized adipose tissue.

Three-dimensional (3D), macroporous, elastic, and biodegradable nanocomposite scaffold for in situ bone regeneration: Toward structural, biophysical, and biochemical cues integration

Although bone tissue with remarkable healing capabilities, the rapid and successful bone regeneration continues to present a challenge because that the influence factors for bone healing are multifaceted, especially for massive bone defects. From a cell/material interactions point of view, integrating multiple cues into one biomaterial is considered as a promising approach in the clinical treatment of bone defects thanks to the provided multiple stimuli. Herein, 3D macroporously elastic biodegradable nanocomposite bone scaffolds (PCSG) were successfully developed based on poly(citrate-siloxane) (PCS) hybrid elastomer and reduced graphene oxide (rGO). The PCSG scaffolds combine with structure (3D, largely open and interconnected pore architecture, high porosity), biophysics (high mechanical properties, roughness surface, piezoelectricity property), and biochemistry cues (silica cross-linked network, Si ions release). Experiments demonstrate that the structurally, biophysically, and biochemically biomimetic properties of PCSG scaffolds are beneficial for triggering cell adhesion, proliferation, matrix mineralization , osteogenic differentiation of osteoblasts (MC3T3-E1) in vitro and significantly promoting in situ bone regeneration in a calvarial bone defect model. The effective and simple strategy of multiple cues integration could pave a universally applicable way in development of bone tissue engineering biomaterials with good osteoinductivity and osteoconductivity for large defects repair, and the reported PCSG scaffolds demonstrate the potential clinic application in fields of bone regeneration and 3D culture of cells. • Integrating structure, biophysics, and biochemistry cues into one bone scaffold for in situ bone regeneration. • The fabrication of 3D bone scaffold with largely open and porosity via the facile sol-gel method. • The proposed bone scaffolds with super Young's modulus not only in dry state but in hydrated condition.

Catechol functionalized ink system and thrombin-free fibrin gel for fabricating cellular constructs with mechanical support and inner micro channels

The development of 3D bio printing technology has contributed to protocols for the repair and regeneration of tissues in recent years. However, it is still a great challenge to fabricate structures that mimic the complexity of native tissue, including both the biomechanics and microscale internal structure. In this study, a catechol functionalized ink system was developed to produce tough and elastic scaffolds with built-in micro channels that simulate the vascular structure. And a skin model was designed to evaluate the cytocompatibility of the scaffolds. The mechanical support stemmed from the double network based on catechol-hyaluronic acid (HACA) and alginate, the micro channels were generated using sacrificial gelatin. HACA/alginate and gelatin were firstly printed using a 3D extrusion printer. Thrombin-free fibrinogen were then mixed with human dermal fibroblasts and introduced to the printed scaffolds to induce gelation. An immortal human keratinocyte cell line was introduced on top of the cellular construct to mimic the full thickness skin structure. The printed scaffolds demonstrated high elasticity and supported the formation of a double-layered cell-laden skin like structure. The results suggest the 3D printing platform developed here provides a platform for skin regeneration and could be explored further to engineer functional skin tissue by incorporation of other types of cells.

High Resolution and Labeling Free Studying the 3D Microstructure of the Pars Tensa-Annulus Unit of Mice.

Hearing loss is a serious illness affecting people’s normal life enormously. The acoustic properties of a tympanic membrane play an important role in hearing, and highly depend on its geometry, composition, microstructure and connection to the surrounding annulus. While the conical geometry of the tympanic membrane is critical to the sound propagation in the auditory system, it presents significant challenges to the study of the 3D microstructure of the tympanic membrane using traditional 2D imaging techniques. To date, most of our knowledge about the 3D microstructure and composition of tympanic membranes is built from 2D microscopic studies, which precludes an accurate understanding of the 3D microstructure, acoustic behaviors and biology of the tissue. Although the tympanic membrane has been reported to contain elastic fibers, the morphological characteristic of the elastic fibers and the spatial arrangement of the elastic fibers with the predominant collagen fibers have not been shown in images. We have developed a 3D imaging technique for the three-dimensional examination of the microstructure of the full thickness of the tympanic membranes in mice without requiring tissue dehydration and stain. We have also used this imaging technique to study the 3D arrangement of the collagen and elastic fibrillar network with the capillaries and cells in the pars tensa-annulus unit at a status close to the native. The most striking findings in the study are the discovery of the 3D form of the elastic and collagen network, and the close spatial relationships between the elastic fibers and the elongated fibroblasts in the tympanic membranes. The 3D imaging technique has enabled to show the 3D waveform contour of the collagen and elastic scaffold in the conical tympanic membrane. Given the close relationship among the acoustic properties, composition, 3D microstructure and geometry of tympanic membranes, the findings may advance the understanding of the structure—acoustic functionality of the tympanic membrane. The knowledge will also be very helpful in the development of advanced cellular therapeutic technologies and 3D printing techniques to restore damaged tympanic membranes to a status close to the native.

Dual Network Composites of Poly(vinyl alcohol)-Calcium Metaphosphate/Alginate with Osteogenic Ions for Bone Tissue Engineering in Oral and Maxillofacial Surgery.

Despite considerable advances in biomaterials-based bone tissue engineering technologies, autografts remain the gold standard for rehabilitating critical-sized bone defects in the oral and maxillofacial (OMF) region. A majority of advanced synthetic bone substitutes (SBS’s) have not transcended the pre-clinical stage due to inferior clinical performance and translational barriers, which include low scalability, high cost, regulatory restrictions, limited advanced facilities and human resources. The aim of this study is to develop clinically viable alternatives to address the challenges of bone tissue regeneration in the OMF region by developing ‘dual network composites’ (DNC’s) of calcium metaphosphate (CMP)—poly(vinyl alcohol) (PVA)/alginate with osteogenic ions: calcium, zinc and strontium. To fabricate DNC’s, single network composites of PVA/CMP with 10% (w/v) gelatine particles as porogen were developed using two freeze–thawing cycles and subsequently interpenetrated by guluronate-dominant sodium alginate and chelated with calcium, zinc or strontium ions. Physicochemical, compressive, water uptake, thermal, morphological and in vitro biological properties of DNC’s were characterised. The results demonstrated elastic 3D porous scaffolds resembling a ‘spongy bone’ with fluid absorbing capacity, easily sculptable to fit anatomically complex bone defects, biocompatible and osteoconductive in vitro, thus yielding potentially clinically viable for SBS alternatives in OMF surgery.

Highly Elastic Scaffolds Produced by Melt Electrowriting of Poly(L‐lactide‐co‐ε‐caprolactone)

AbstractA rapid and efficient system to adapt commercially available polymers for melt electrowriting (MEW) for the fabrication of micro‐fibrous scaffolds is introduced. Poly(ε‐caprolactone) (PCL) is currently the gold standard for MEW due to its low melt viscosity and its use in tissue regeneration. While several other polymers have been used for MEW, they involve small‐scale custom synthesis meaning beyond PCL there is a scarcity of commercial polymers suitable for MEW. Furthermore, PCL has a long degradation time and lacks the elasticity needed for many applications. Poly(L‐lactide‐co‐ε‐caprolactone) (PLCL) is an elastic polymer with relatively fast degradation profile and is commercially available in high purity. Its high melt viscosity, however, makes it incompatible with MEW at normal operating temperatures. Rather than modifying the MEW machine, this study uses a simple pre‐treatment of PLCL to tailor the melt viscosity. This treatment involves heating PLCL at 150 °C for 24–48 h to enable MEW printing into scaffolds at 110 °C with fiber diameters 14–40 µm. Scaffolds maintained their elasticity after the thermal degradation process, becoming the first PLCL low‐temperature MEW scaffolds. Moreover, this approach can be readily adapted by any MEW user without manipulating the polymer beyond the thermal treatment in an oven.

Soft Elastic Fibrous Scaffolds for Muscle Tissue Engineering by Touch Spinning.

This paper reports an approach for the fabrication of highly aligned soft elastic fibrous scaffolds using touch spinning of thermoplastic polycaprolactone-polyurethane elastomers and demonstrates their potential for the engineering of muscle tissue. A family of polyester-polyurethane soft copolymers based on polycaprolactone with different molecular weights and three different chain extenders such as 1,4-butanediol and polyethylene glycols with different molecular weight was synthesized. By varying the molar ratio and molecular weights between the segments of the copolymer, different physicochemical and mechanical properties were obtained. The polymers possess elastic modulus in the range of a few megapascals and good reversibility of deformation after stretching. The combination of the selected materials and fabrication methods allows several essential advantages such as biocompatibility, biodegradability, suitable mechanical properties (elasticity and softness of the fibers), high recovery ratio, and high resilience mimicking properties of the extracellular matrix of muscle tissue. Myoblasts demonstrate high viability in contact with aligned fibrous scaffolds, where they align along the fibers, allowing efficient cell patterning on top of the structures. Altogether, the importance of this approach is the fabrication of highly oriented fiber constructs that can support the proliferation and alignment of muscle cells for muscle tissue engineering applications.

A Collagen-Mimetic Organic-Inorganic Hydrogel for Cartilage Engineering.

Promising strategies for cartilage regeneration rely on the encapsulation of mesenchymal stromal cells (MSCs) in a hydrogel followed by an injection into the injured joint. Preclinical and clinical data using MSCs embedded in a collagen gel have demonstrated improvements in patients with focal lesions and osteoarthritis. However, an improvement is often observed in the short or medium term due to the loss of the chondrocyte capacity to produce the correct extracellular matrix and to respond to mechanical stimulation. Developing novel biomimetic materials with better chondroconductive and mechanical properties is still a challenge for cartilage engineering. Herein, we have designed a biomimetic chemical hydrogel based on silylated collagen-mimetic synthetic peptides having the ability to encapsulate MSCs using a biorthogonal sol-gel cross-linking reaction. By tuning the hydrogel composition using both mono- and bi-functional peptides, we succeeded in improving its mechanical properties, yielding a more elastic scaffold and achieving the survival of embedded MSCs for 21 days as well as the up-regulation of chondrocyte markers. This biomimetic long-standing hybrid hydrogel is of interest as a synthetic and modular scaffold for cartilage tissue engineering.