Tissue Engineering Design Research Articles

Blueprints of Architected Materials: A Guide to Metamaterial Design for Tissue Engineering.

Mechanical metamaterials are rationally designed structures engineered to exhibit extraordinary properties, often surpassing those of their constituent materials. The geometry of metamaterials' building blocks, referred to as unit cells, plays an essential role in determining their macroscopic mechanical behavior. Due to their hierarchical design and remarkable properties, metamaterials hold significant potential for tissue engineering; however their implementation in the field remains limited. The major challenge hindering the broader use of metamaterials lies in the complexity of unit cell design and fabrication. To address this gap, a comprehensive guide is presented detailing the design principles of well-established metamaterials. The essential unit cell geometric parameters and design constraints, as well as their influence on mechanical behavior, are summarized highlighting essential points for effective fabrication. Moreover, the potential integration of artificial intelligence techniques is explored in meta-biomaterial design for patient- and application-specific design. Furthermore, a comprehensive overview of current applications of mechanical metamaterials is provided in tissue engineering, categorized by tissue type, thereby showcasing the versatility of different designs in matching the mechanical properties of the target tissue. This review aims to provide a valuable resource for tissue engineering researchers and aid in the broader use of metamaterials in the field.

Use of Chitosan as a Precursor for Multiple Applications in Medicinal Chemistry: Recent Significant Contributions.

Chitosan (CS) is a polymer made up of mainly deacetylated β-1,4 D-glucosamine units, which is part of a large group of D-glucosamine oligomers known as chitooligosaccharides, which can be obtained from chitin, most abundant natural polymer after cellulose and central component of the shrimp exoskeleton. It is known that it can be used for the development of materials, among which its use stands out in wastewater treatment (removal of metal ions, dyes, and as a membrane in purification processes), food industry (anti-cholesterol and fat, packaging material, preservative, and food additive), agriculture (seed and fertilizer coating, controlled release agrochemicals), pulp and paper industry (surface treatment, adhesive paper), cosmetics (body creams, lotions, etc.), in the engineering of tissues, wound healing, as excipients for drug administration, gels, membranes, nanofibers, beads, microparticles, nanoparticles, scaffolds, sponges, and diverse biological ones, specifically antibacterial and antifungal activities. This article reviews the main contributions published in the last ten years regarding the use and application of CS in medical chemistry. The applications exposed here involve regenerative medicine in the design of bioprocesses and tissue engineering, Pharmaceutical sciences to obtain biomaterials, polymers, biomedicine, and the use of nanomaterials and nanotechnology, toxicology, and Clinical Pharmaceuticals, emphasizing the perspectives and the direction that can take research in this area.

Advances in melt electrowriting for cardiovascular applications.

Melt electrowriting (MEW) is an electric-field-assisted additive biofabrication technique that has brought significant advancements to bioinspired scaffold design for soft tissue engineering and beyond. Owing to its targeted microfiber placement, MEW has become a powerful platform technology for the fabrication of in vitro disease models up to functional biohybrid constructs that are investigated in vivo to reach clinical translation soon. This work provides a concise overview of this rapidly evolving field by highlighting the key contributions of MEW to cardiovascular tissue engineering. Specifically, we i) pinpoint the methods to introduce microvascular networks in thick 3D constructs benefitting from (sacrificial) MEW microfibers, ii) report MEW-based concepts for small-diameter vascular grafts and stents, iii) showcase how contracting cardiac tissues can profit from the tunable structure-property relationship of MEW scaffolds, and iv) address how complete regenerative heart valves can be built on complex fiber scaffold architectures that recapitulate J-shaped tensile properties and tissue heterogeneity. Lastly, we touch on novel biomaterial advancements and discuss the technological challenges of MEW to unlock the full potential of this transformative technology.

Bioactive polymer composite scaffolds fabricated from 3D printed negative molds enable bone formation and vascularization

Scaffolds for bone defect treatment should ideally support vascularization and promote bone formation, to facilitate the translation into biomedical device applications. This study presents a novel approach utilizing 3D-printed water-dissolvable polyvinyl alcohol (PVA) sacrificial molds to engineer polymerized High Internal Phase Emulsion (polyHIPE) scaffolds with microchannels and distinct multiscale porosity. Two sacrificial mold variants (250 µm and 500 µm) were generated using fused deposition modeling, filled with HIPE, and subsequently dissolved to create polyHIPE scaffolds containing microchannels. In vitro assessments demonstrated significant enhancement in cell infiltration, proliferation, and osteogenic differentiation, underscoring the favorable impact of microchannels on cell behavior. High loading efficiency and controlled release of the osteogenic factor BMP-2 were achieved, with microchannels facilitating release of the growth factor. Evaluation in a mouse critical-size calvarial defect model revealed enhanced vascularization and bone formation in microchanneled scaffolds containing BMP-2. This study not only introduces an accessible method for creating multiscale porosity in polyHIPE scaffolds but also emphasizes its capability to enhance cellular infiltration, controlled growth factor release, and in vivo performance. The findings suggest promising applications in bone tissue engineering and regenerative medicine, and are expected to facilitate the translation of this type of biomaterial scaffold. Statement of significanceThis study holds significance in the realm of biomaterial scaffold design for bone tissue engineering and regeneration. We demonstrate a novel method to introduce controlled multiscale porosity and microchannels into polyHIPE scaffolds, by utilizing 3D-printed water-dissolvable PVA molds. The strategy offers new possibilities for improving cellular infiltration, achieving controlled release of growth factors, and enhancing vascularization and bone formation outcomes. This microchannel approach not only marks a substantial stride in scaffold design but also demonstrates its tangible impact on enhancing osteogenic cell differentiation and fostering robust bone formation in vivo. The findings emphasize the potential of this methodology for bone regeneration applications, showcasing an interesting advancement in the quest for effective and innovative biomaterial scaffolds to regenerate bone defects.

Establishment and characterization of a rat model of scalp-cranial composite defect for multilayered tissue engineering.

Composite cranial defects have individual functional and aesthetic ramifications, as well as societal burden, while posing significant challenges for reconstructive surgeons. Single-stage composite reconstruction of these deformities entail complex surgeries that bear many short- and long-term risks and complications. Current research on composite scalp-cranial defects is sparse and one-dimensional, often focusing solely on bone or skin. Thus, there is an unmet need for a simple, clinically relevant composite defect model in rodents, where there is a challenge in averting healing of the skin component via secondary intention. By utilizing a customizable (3D-printed) wound obturator, the scalp wound can be rendered non-healing for a long period (more than 6 weeks), with the cranial defect patent. The wound obturator shows minimal biotoxicity and will not cause severe endocranium-granulation adhesion. This composite defect model effectively slowed the scalp healing process and preserved the cranial defect, embodying the characteristics of a "chronic composite defect". In parallel, an autologous reconstruction model was established as the positive control. This positive control exhibited reproducible healing of the skin within 3 weeks with variable degrees of osseointegration, consistent with clinical practice. Both models provide a stable platform for subsequent research not only for composite tissue engineering and scaffold design but also for mechanistic studies of composite tissue healing.

Fabrication and Biomedical Application of Alginate Composite Hydrogels in Bone Tissue Engineering: A Review.

Nowadays, as a result of the frequent occurrence of accidental injuries and traumas such as bone damage, the number of people causing bone injuries or fractures is increasing around the world. The design and fabrication of ideal bone tissue engineering (BTE) materials have become a research hotspot in the scientific community, and thus provide a novel path for the treatment of bone diseases. Among the materials used to construct scaffolds in BTE, including metals, bioceramics, bioglasses, biomacromolecules, synthetic organic polymers, etc., natural biopolymers have more advantages against them because they can interact with cells well, causing natural polymers to be widely studied and applied in the field of BTE. In particular, alginate has the advantages of excellent biocompatibility, good biodegradability, non-immunogenicity, non-toxicity, wide sources, low price, and easy gelation, enabling itself to be widely used as a biomaterial. However, pure alginate hydrogel as a BTE scaffold material still has many shortcomings, such as insufficient mechanical properties, easy disintegration of materials in physiological environments, and lack of cell-specific recognition sites, which severely limits its clinical application in BTE. In order to overcome the defects of single alginate hydrogels, researchers prepared alginate composite hydrogels by adding one or more materials to the alginate matrix in a certain proportion to improve their bioapplicability. For this reason, this review will introduce in detail the methods for constructing alginate composite hydrogels, including alginate/polymer composite hydrogels, alginate/bioprotein or polypeptide composite hydrogels, alginate/bioceramic composite hydrogels, alginate/bioceramic composite hydrogels, and alginate/nanoclay composite hydrogels, as well as their biological application trends in BTE scaffold materials, and look forward to their future research direction. These alginate composite hydrogel scaffolds exhibit both unexceptionable mechanical and biochemical properties, which exhibit their high application value in bone tissue repair and regeneration, thus providing a theoretical basis for the development and sustainable application of alginate-based functional biomedical materials.

Bioactive Materials That Promote the Homing of Endogenous Mesenchymal Stem Cells to Improve Wound Healing.

Endogenous stem cell homing refers to the transport of endogenous mesenchymal stem cells (MSCs) to damaged tissue. The paradigm of using well-designed biomaterials to induce resident stem cells to home in to the injured site while coordinating their behavior and function to promote tissue regeneration is known as endogenous regenerative medicine (ERM). ERM is a promising new avenue in regenerative therapy research, and it involves the mobilizing of endogenous stem cells for homing as the principal means through which to achieve it. Comprehending how mesenchymal stem cells home in and grasp the influencing factors of mesenchymal stem cell homing is essential for the understanding and design of tissue engineering. This review summarizes the process of MSC homing, the factors influencing the homing process, analyses endogenous stem cell homing studies of interest in the field of skin tissue repair, explores the integration of endogenous homing promotion strategies with cellular therapies and details tissue engineering strategies that can be used to modulate endogenous homing of stem cells. In addition to providing more systematic theories and ideas for improved materials for endogenous tissue repair, this review provides new perspectives to explore the complex process of tissue remodeling to enhance the rational design of biomaterial scaffolds and guide tissue regeneration strategies.

Optimizing Filament-Based TCP Scaffold Design for Osteoconduction and Bone Augmentation: Insights from In Vivo Rabbit Models.

Additive manufacturing has emerged as a transformative tool in biomedical engineering, offering precise control over scaffold design for bone tissue engineering and regenerative medicine. While much attention has been focused on optimizing pore-based scaffold architectures, filament-based microarchitectures remain relatively understudied, despite the fact that the majority of 3D-printers generate filament-based structures. Here, we investigated the influence of filament characteristics on bone regeneration outcomes using a lithography-based additive manufacturing approach. Three distinct filament-based scaffolds (Fil050, Fil083, and Fil125) identical in macroporosity and transparency, crafted from tri-calcium phosphate (TCP) with varying filament thicknesses and distance, were evaluated in a rabbit model of bone augmentation and non-critical calvarial defect. Additionally, two scaffold types differing in filament directionality (Fil and FilG) were compared to elucidate optimal design parameters. Distance of bone ingrowth and percentage of regenerated area within scaffolds were measured by histomorphometric analysis. Our findings reveal filaments of 0.50 mm as the most effective filament-based scaffold, demonstrating superior bone ingrowth and bony regenerated area compared to larger size filament (i.e., 0.83 mm and 1.25 mm scaffolds). Optimized directionality of filaments can overcome the reduced performance of larger filaments. This study advances our understanding of microarchitecture's role in bone tissue engineering and holds significant implications for clinical practice, paving the way for the development of highly tailored, patient-specific bone substitutes with enhanced efficacy.

Nanofiber-microwell cell culture system for spatially patterned differentiation of pluripotent stem cells in 3D

The intricate interplay between biochemical and physical cues dictates pluripotent stem cell (PSC) differentiation to form various tissues. While biochemical modulation has been extensively studied, the role of biophysical microenvironments in early lineage commitment remains elusive. Here, we introduce a novel 3D cell culture system combining electrospun nanofibers with microfabricated polydimethylsiloxane (PDMS) patterns. This system enables the controlled formation of semispherical human induced pluripotent stem cell (hiPSC) colonies, facilitating the investigation of local mechanical stem cell niches on mechano-responsive signaling and lineage specification. Our system unveiled spatially organized RhoA activity coupled with actin-myosin cable formation, suggesting mechano-dependent hiPSC behaviors. Nodal network analysis of RNA-seq data revealed RhoA downstream regulation of YAP signaling, DNA histone modifications, and patterned germ layer specification. Notably, altering colony morphology through controlled PDMS microwell shaping effectively modulated the spatial distribution of mechano-sensitive mediators and subsequent differentiation. This study provides a cell culture platform to decipher the role of biophysical cues in early embryogenesis, offering valuable insights for material design in tissue engineering and regenerative medicine applications.

Mechanical and Computational Fluid Dynamic Models for Magnesium-Based Implants.

Today, mechanical properties and fluid flow dynamic analysis are considered to be two of the most important steps in implant design for bone tissue engineering. The mechanical behavior is characterized by Young's modulus, which must have a value close to that of the human bone, while from the fluid dynamics point of view, the implant permeability and wall shear stress are two parameters directly linked to cell growth, adhesion, and proliferation. In this study, we proposed two simple geometries with a three-dimensional pore network dedicated to a manufacturing route based on a titanium wire waving procedure used as an intermediary step for Mg-based implant fabrication. Implant deformation under different static loads, von Mises stresses, and safety factors were investigated using finite element analysis. The implant permeability was computed based on Darcy's law following computational fluid dynamic simulations and, based on the pressure drop, was numerically estimated. It was concluded that both models exhibited a permeability close to the human trabecular bone and reduced wall shear stresses within the biological range. As a general finding, the proposed geometries could be useful in orthopedics for bone defect treatment based on numerical analyses because they mimic the trabecular bone properties.

A bilayer hydrogel mimicking the periosteum-bone structure for innervated bone regeneration.

In bone tissue, nerves are primarily located in the periosteum and play an indispensable role in bone defect repair. However, most bone tissue engineering approaches ignored the reconstruction of the nerve network. Herein, we aimed to develop a bilayer hydrogel simulating periosteum-bone structure to induce innervated bone regeneration. The bottom "bone" layer consisted of gelatin methacryloyl (GelMA), poly(ethylene glycol) diacrylate (PEGDA), and nano-hydroxyapatite (nHA), whereas the upper "periosteum" layer consisted of GelMA, sodium alginate (SA) and MgCl2. The mechanical properties of the upper and bottom hydrogels were designed to be suitable for neurogenesis and osteogenesis, respectively. Besides, Mg2+ from the "periosteum" layer released at the early stage (within 7 d), which aligned with the optimal time window for nerve regeneration and osteogenic related neuropeptide release. Simultaneously, the prevention of long-term Mg2+ release (after 7 d) could avoid osteogenic inhibition caused by prolonged Mg2+ exposure. Additionally, the incorporation of nHA in the bottom "bone" layer supported the long-term osteogenesis due to its osteoconductivity and slow degradation. In vitro biological experiments revealed that the bilayer hydrogel (GS@Mg/GP@nHA) promoted neurite growth and calcitonin gene-related peptide (CGRP) expression in rat dorsal root ganglion (DRG) neurons, as well as the osteogenesis of rat bone-derived mesenchymal stem cells (BMSCs). Moreover, the in vivo experiments demonstrated that the GS@Mg/GP@nHA hydrogel efficiently promoted nerve network reconstruction and bone regeneration of rat calvarial bone defects. Altogether, the bilayer hydrogel GS@Mg/GP@nHA could promote innervated bone regeneration, providing new insights for biomaterial design for bone tissue engineering.

Mechanical guidance to self-organization and pattern formation of stem cells.

The self-organization of stem cells (SCs) constitutes the fundamental basis of the development of biological organs and structures. SC-driven patterns are essential for tissue engineering, yet unguided SCs tend to form chaotic patterns, impeding progress in biomedical engineering. Here, we show that simple geometric constraints can be used as an effective mechanical modulation approach that promotes the development of controlled self-organization and pattern formation of SCs. Using the applied SC guidance with geometric constraints, we experimentally uncover a remarkable deviation in cell aggregate orientation from a random direction to a specific orientation. Subsequently, we propose a dynamic mechanical framework, including cells, the extracellular matrix (ECM), and the culture environment, to characterize the specific orientation deflection of guided cell aggregates relative to initial geometric constraints, which agrees well with experimental observation. Based on this framework, we further devise various theoretical strategies to realize complex biological patterns, such as radial and concentric structures. Our study highlights the key role of mechanical factors and geometric constraints in governing SCs' self-organization. These findings yield critical insights into the regulation of SC-driven pattern formation and hold great promise for advancements in tissue engineering and bioactive material design for regenerative application.

Chiral nanomaterials in tissue engineering.

Addressing significant medical challenges arising from tissue damage and organ failure, the field of tissue engineering has evolved to provide revolutionary approaches for regenerating functional tissues and organs. This involves employing various techniques, including the development and application of novel nanomaterials. Among them, chiral nanomaterials comprising non-superimposable nanostructures with their mirror images have recently emerged as innovative biomaterial candidates to guide tissue regeneration due to their unique characteristics. Chiral nanomaterials including chiral fibre supramolecular hydrogels, polymer-based chiral materials, self-assembling peptides, chiral-patterned surfaces, and the recently developed intrinsically chiroptical nanoparticles have demonstrated remarkable ability to regulate biological processes through routes such as enantioselective catalysis and enhanced antibacterial activity. Despite several recent reviews on chiral nanomaterials, limited attention has been given to the specific potential of these materials in facilitating tissue regeneration processes. Thus, this timely review aims to fill this gap by exploring the fundamental characteristics of chiral nanomaterials, including their chiroptical activities and analytical techniques. Also, the recent advancements in incorporating these materials in tissue engineering applications are highlighted. The review concludes by critically discussing the outlook of utilizing chiral nanomaterials in guiding future strategies for tissue engineering design.

Self-Assembling Peptides with Insulin-Like Growth Factor Mimicry.

Growth factor (GF) mimicry involves recapitulating the signaling of larger molecules or cells. Although GF mimicry holds considerable promise in tissue engineering and drug design applications, difficulties in targeting the signaling molecule to the site of delivery and dissociation of mimicking peptides from their target receptors continue to limit its clinical application. To address these challenges, we utilized a self-assembling peptide (SAP) platform to generate synthetic insulin-like growth factor (IGF)-signaling, self-assembling GFs. Our peptide hydrogels are biocompatible and bind target IGF receptors in a dose-dependent fashion, activate proangiogenic signaling, and facilitate formation of angiogenic microtubules in vitro. Furthermore, infiltrated hydrogels are stable for weeks to months. We conclude that the enhanced targeting and long-term stability of our SAP/GF mimicry implants may improve the efficacy and safety of future GF mimic therapeutics.

FOOTPRINT ANALYSIS OF THE LATERAL LIGAMENTS OF THE ANKLE: A NEW APPROACH

AbstractThe lateral ligaments of the ankle composed of the anterior talofibular (ATFL), calcaneofibular (CFL) and posterior talofibular ligaments (PTFL), are amongst the most commonly injured ligaments of the human body. Although treatment methods have been explored exhaustively, healing outcomes remain poor with high rates of re-injury, chronic ankle instability and pain persisting. The introduction and application of tissue engineering methods may target poor healing outcomes and eliminate long-term complications, improving the overall quality of life of affected individuals. For any surgical procedure or tissue-engineered replacement to be successful, a comprehensive understanding of the complete anatomy of the native structure is essential. Knowledge of the dimensions of ligament footprints is vitally important for surgeons as it guides the placement of bone tunnels during repair. It is also imperative in tissue-engineered design as the creation of a successful replacement relies on a thorough understanding of the native anatomy and microanatomical structure. Several studies explore techniques to describe ligament footprints around the body, with limited studies describing in-depth footprint dimensions of the ATFL, CFL and PTFL. Techniques currently used to measure ligament footprints are complex and require resources which may not be readily available, therefore a new methodology may prove beneficial.ObjectivesThis study explores the application of a novel technique to assess the footprint of ankle ligaments through a straightforward inking method. This method aims to enhance surgical technique and contribute to the development of a tissue-engineered analogue based on real anatomical morphometric data.MethodsCadaveric dissection of the ATFL, CFL and PTFL was performed on 12 unpaired fresh frozen ankles adhering to regulations of the Human Tissue (Scotland) Act. The ankle complex with attaching ligaments was immersed in methylene blue. Dissection of the proximal and distal entheses of each ligament was carried out to reveal the unstained ligament footprint. Images of each ligament footprint were taken, and the area, length and width of each footprint were assessed digitally.ResultsThe collective area of the proximal entheses of the ATFL, CFL and PTFL measures 142.11 ± 12.41mm2. The mean areas of the superior (SB) and inferior band (IB) of the distal enthesis of the ATFL measured 41.72 ± 5.01mm2 and 26.66 ± 3.12mm2 respectively. The footprint of the distal enthesis of the CFL measured 146.07 ± 14.05mm2, while the footprint of the distal PTFL measured 126.26 ± 8.88mm2. The proximal footprint of the ATFL, CFL and PTFL measured 11.06 ± 0.69mm, 7.87 ± 0.43mm and 10.52 ± 0.63mm in length and 8.66 ± 0.50mm, 9.10 ± 0.92mm and 14.41 ± 1.30mm in width on average. The distal footprint of the ATFL (SB), ATFL (IB), CFL and PTFL measured 10.92 ± 0.81 mm, 8.46 ± 0.46mm, 13.98 ± 0.93mm and 11.25 ± 0.95mm in length and 7.76 ± 0.59mm, 7.51 ± 0.64mm, 18.98 ± 1.15mm and 24.80 ± 1.25mm in width on average.ConclusionsThis methodology provides an effective approach in the identification of the footprint of the lateral ligaments of the ankle to enhance surgical precision and accuracy in tissue-engineered design.Declaration of Interest(b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Nanodiamonds for tissue engineering and regeneration

Tissue engineering mainly mimics the native cell environment for cell growth and regeneration. In regard to this strategy, different materials have been used for fabrication of cell support in an in vivo resembling ambience. An ideal tissue engineering scaffold provides biocompatible, three-dimensional (3D), porous structure with tissue-specific properties such as the electrical conductivity in neural tissue and controlled biodegradability. Therefore, the precise selection of biopolymers and nanomaterials with properties of non-interfering biological processes, like cell proliferation and differentiation plays an important role in the successful scaffold design and final outcome in tissue engineering. Nanodiamonds (NDs) are carbon-based nanomaterials and possess remarkable features including biocompatibility, high surface area, optical properties, chemical stability, excellent mechanical and physical properties, highly functional surfaces, and highly resistant to harsh environments, which make them highly validated as multi-functional materials for biomedical applications. These characteristics have recently attracted much attention in the area of regenerative medicine from the scaffold to prosthesis designing. This review will discuss the extensive applications of NDs in different scopes of regenerative medicine, including tissue engineering, however, the main focus will be on neural regeneration.

Cellular Interactions in Cell Sheets Enhance Mesenchymal Stromal Cell Immunomodulatory Properties.

Immune-related applications of mesenchymal stromal cells (MSCs) in cell therapy seek to exploit immunomodulatory paracrine signaling pathways to reduce inflammation. A key MSC therapeutic challenge is reducing patient outcome variabilities attributed to insufficient engraftment/retention of injected heterogenous MSCs. To address this, we propose directly transplantable human single-cell-derived clonal bone marrow MSC (hcBMSC) sheets. Cell sheet technology is a scaffold-free tissue engineering strategy enabling scalable production of highly engraftable cell constructs retaining endogenous cell-cell and cell-matrix interactions, important to cell function. cBMSCs, as unique MSC subset populations, facilitate rational selection of therapeutically relevant MSC clones from donors. Here, we combine human cBMSCs with cell sheet technology, demonstrating cell sheet fabrication as a method to significantly upregulate expression of immunomodulatory molecules interleukin (IL)-10, indoleamine 2,3-dioxygenase (IDO-1), and prostaglandin E synthase 2 (PTGES2) across GMP-grade hcBMSC lines and whole human bone marrow-derived MSCs compared to respective conventional cell suspensions. When treated with carbenoxolone, a gap junction inhibitor, cell sheets downregulate IL-10 and IDO-1 expression, implicating functional roles for intercellular sheet interactions. Beyond producing directly transferable multicellular hcBMSC constructs, cell sheet technology amplifies hcBMSC expression of immunomodulatory factors important to therapeutic action. In addition, this work demonstrates the importance of cell-cell interactions as a tissue engineering design criterion to enhance consistent MSC functions.

Biomimetic Cardiac Tissue Models for In Vitro Arrhythmia Studies.

Cardiac arrhythmias are a major cause of cardiovascular mortality worldwide. Many arrhythmias are caused by reentry, a phenomenon where excitation waves circulate in the heart. Optical mapping techniques have revealed the role of reentry in arrhythmia initiation and fibrillation transition, but the underlying biophysical mechanisms are still difficult to investigate in intact hearts. Tissue engineering models of cardiac tissue can mimic the structure and function of native cardiac tissue and enable interactive observation of reentry formation and wave propagation. This review will present various approaches to constructing cardiac tissue models for reentry studies, using the authors' work as examples. The review will highlight the evolution of tissue engineering designs based on different substrates, cell types, and structural parameters. A new approach using polymer materials and cellular reprogramming to create biomimetic cardiac tissues will be introduced. The review will also show how computational modeling of cardiac tissue can complement experimental data and how such models can be applied in the biomimetics of cardiac tissue.

Advances in the Development of Nano-Engineered Mechanically Robust Hydrogels for Minimally Invasive Treatment of Bone Defects.

Injectable hydrogels were discovered as attractive materials for bone tissue engineering applications given their outstanding biocompatibility, high water content, and versatile fabrication platforms into materials with different physiochemical properties. However, traditional hydrogels suffer from weak mechanical strength, limiting their use in heavy load-bearing areas. Thus, the fabrication of mechanically robust injectable hydrogels that are suitable for load-bearing environments is of great interest. Successful material design for bone tissue engineering requires an understanding of the composition and structure of the material chosen, as well as the appropriate selection of biomimetic natural or synthetic materials. This review focuses on recent advancements in materials-design considerations and approaches to prepare mechanically robust injectable hydrogels for bone tissue engineering applications. We outline the materials-design approaches through a selection of materials and fabrication methods. Finally, we discuss unmet needs and current challenges in the development of ideal materials for bone tissue regeneration and highlight emerging strategies in the field.

Strategies for Anisotropic Fibrillar Hydrogels: Design, Cell Alignment, and Applications in Tissue Engineering.

Efficient cellular alignment in biomaterials presents a considerable challenge, demanding the refinement of appropriate material morphologies, while ensuring effective cell-surface interactions. To address this, biomaterials are continuously researched with diverse coatings, hydrogels, and polymeric surfaces. In this context, we investigate the influence of physicochemical parameters on the architecture of fibrillar hydrogels that significantly orient the topography of flexible hydrogel substrates, thereby fostering cellular adhesion and spatial organization. Our Review comprehensively assesses various techniques for aligning polymer fibrils within hydrogels, specifically interventions applied during and after the cross-linking process. These methodologies include mechanical strains, precise temperature modulation, controlled fluidic dynamics, and chemical modulators, as well as the use of magnetic and electric fields. We highlight the intrinsic appeal of these methodologies in fabricating cell-aligning interfaces and discuss their potential implications within the fields of biomaterials and tissue engineering, particularly concerning the pursuit of optimal cellular alignment.