Cell-biomaterial Interactions Research Articles

Development of silk microfiber-reinforced bioink for muscle tissue engineering and in situ printing by a handheld 3D printer

Volumetric muscle loss (VML) presents a significant challenge in tissue engineering due to the irreparable nature of extensive muscle injuries. In this study, we propose a novel approach for VML treatment using a bioink composed of silk microfiber-reinforced silk fibroin (SF) hydrogel. The engineered scaffolds are predesigned to provide structural support and fiber alignment to promote tissue regeneration in situ. We also validated our custom-made handheld 3D printer performance and showcased its potential applications for in situ printing using robotics. The fiber contents of SF and gelatin ink were varied from 1 to 5 %. Silk fibroin microfibers reinforced ink offered increased viscosity of the gel, which enhanced the shape fidelity and mechanical strength of the bulk scaffold. The fiber-reinforced bioink also demonstrated better cell-biomaterial interaction upon printing. The handheld 3D printer enabled the precise and on-demand fabrication of scaffolds directly at the defect site, for personalized and minimally invasive treatment. This innovative approach holds promise for addressing the challenges associated with VML treatment and advancing the field of regenerative medicine.

Effects of Physically Adsorbed and Chemically Immobilized RGD on Cell Adhesion to a Hydroxyapatite Surface

The strategies used to associate peptide arginylglycylaspartic acid (RGD) with calcium phosphate grafts to enhance cell–biomaterial interactions have been controversial in the literature. Several works have demonstrated that RGD-functionalized hydroxyapatite (HA) surfaces improve cell adhesion, whereas others claim that RGD-loaded HA has an inhibitory effect when serum is present in the biological medium. To investigate such contradictory results, we associated RGD with the HA surface using physical adsorption and chemical bonding methods and evaluated the cell adhesion and spreading in pre-osteoblasts culture with and without fetal bovine serum (FBS). The effect of functionalization methods on the physicochemical characteristics of both surfaces was analyzed using multiscale techniques. Adsorption assays of serum allowed us to estimate the impact of the association method on the HA surface’s reactivity. Physically adsorbed RGD did not increase the number of adhered cells due to the weak interactions between the peptide and the surface. Although chemical binding stabilizes RGD on the HA, the functionalization procedure covered the surface with molecules such as (3-aminopropyl)triethoxysilane (APTEs) and carbodiimide, changing the surface’s chemical activity. Serum protein adsorption decreased by 90%, revealing a significant reduction in the surface interactions with molecules of the biological medium. The present study’s findings showed that the RGD’s physical association with HA did not improve cell adhesion and that this phenomenon is highly dependent on the presence of serum proteins.

Phosphatidylserine-functional polydimethylsiloxane substrates regulate macrophage M2 polarization via modulus-dependent NF-κB/PPARγ pathway

Macrophages, highly plastic innate immune cells, critically influence the success of implantable devices by responding to biochemical and physical cues. However, the mechanisms underlying their synergistic regulation of macrophage polarization on implant surfaces remain poorly understood. Therefore, we constructed anti-inflammatory phosphatidylserine (PS) modified polydimethylsiloxane (PDMS) substrates with low, medium, and high modulus (1–100 kPa) to investigate the combined effects and underlying mechanisms of substrate modulus and biochemical signal on macrophage polarization. The introduction of PS on the PDMS surface not only significantly enhanced the polarization of M0 to M2 but also potently suppressed lipopolysaccharide (LPS)-induced M1 activation, with this effect further potentiated by a reduction in substrate modulus. In vivo subcutaneous implantation experiments also corroborated the synergistic effect of PS functionalization and low modulus PDMS in inhibiting M1 activation and promoting M2 polarization. Notably, reduced modulus led to decreased integrin αV/β3 clustering and cytoskeletal protein aggregation, ultimately diminishing YAP activation and nuclear translocation. Concomitantly, this disruption of the Piezo1-cytoskeletal protein positive feedback loop resulted in reduced p65/IκB phosphorylation and inflammation, while concurrently promoting PPARγ expression. Overall, our findings underscore the pivotal role of substrate modulus in modulating PS-mediated biomaterial-cell interactions, synergistically potentiating PS-induced M2 macrophage polarization, thus paving the way for the design of advanced immunomodulatory biomaterials.

Comparison of Printable Biomaterials for Use in Neural Tissue Engineering: An In Vitro Characterization and In Vivo Biocompatibility Assessment.

Nervous system traumatic injuries are prevalent in our society, with a significant socioeconomic impact. Due to the highly complex structure of the neural tissue, the treatment of these injuries is still a challenge. Recently, 3D printing has emerged as a promising alternative for producing biomimetic scaffolds, which can lead to the restoration of neural tissue function. The objective of this work was to compare different biomaterials for generating 3D-printed scaffolds for use in neural tissue engineering. For this purpose, four thermoplastic biomaterials, ((polylactic acid) (PLA), polycaprolactone (PCL), Filaflex (FF) (assessed here for the first time for biomedical purposes), and Flexdym (FD)) and gelatin methacrylate (GelMA) hydrogel were subjected to printability and mechanical tests, in vitro cell-biomaterial interaction analyses, and in vivo biocompatibility assessment. The thermoplastics showed superior printing results in terms of resolution and shape fidelity, whereas FD and GelMA revealed great viscoelastic properties. GelMA demonstrated a greater cell viability index after 7 days of in vitro cell culture. Moreover, all groups displayed connective tissue encapsulation, with some inflammatory cells around the scaffolds after 10 days of in vivo implantation. Future studies will determine the usefulness and in vivo therapeutic efficacy of novel neural substitutes based on the use of these 3D-printed scaffolds.

Open-Top Patterned Hydrogel-Laden 3D Glioma Cell Cultures for Creation of Dynamic Chemotactic Gradients to Direct Cell Migration.

The laminar flow profiles in microfluidic systems coupled to rapid diffusion at flow streamlines have been widely utilized to create well-controlled chemical gradients in cell cultures for spatially directing cell migration. However, within hydrogel-based closed microfluidic systems of limited depth (≤0.1 mm), the biomechanical cues for the cell culture are dominated by cell interactions with channel surfaces rather than with the hydrogel microenvironment. Also, leaching of poly(dimethylsiloxane) (PDMS) constituents in closed systems and the adsorption of small molecules to PDMS alter chemotactic profiles. To address these limitations, we present the patterning and integration of a PDMS-free open fluidic system, wherein the cell-laden hydrogel directly adjoins longitudinal channels that are designed to create chemotactic gradients across the 3D culture width, while maintaining uniformity across its ∼1 mm depth to enhance cell-biomaterial interactions. This hydrogel-based open fluidic system is assessed for its ability to direct migration of U87 glioma cells using a hybrid hydrogel that includes hyaluronic acid (HA) to mimic the brain tumor microenvironment and gelatin methacrylate (GelMA) to offer the adhesion motifs for promoting cell migration. Chemotactic gradients to induce cell migration across the hydrogel width are assessed using the chemokine CXCL12, and its inhibition by AMD3100 is validated. This open-top hydrogel-based fluidic system to deliver chemoattractant cues over square-centimeter-scale areas and millimeter-scale depths can potentially serve as a robust screening platform to assess emerging glioma models and chemotherapeutic agents to eradicate them.

Insights into spheroids formation in cellulose nanofibrils and Matrigel hydrogels using AFM-based techniques

The recent FDA decision to eliminate animal testing requirements emphasises the role of cell models, such as spheroids, as regulatory test alternatives for investigations of cellular behaviour, drug responses, and disease modelling. The influence of environment on spheroid formation are incompletely understood, leading to uncertainty in matrix selection for scaffold-based 3D culture. This study uses atomic force microscopy-based techniques to quantify cell adhesion to Matrigel and cellulose nanofibrils (CNF), and cell-cell adhesion forces, and their role in spheroid formation of hepatocellular carcinoma (HepG2) and induced pluripotent stem cells (iPS(IMR90)-4). Results showed different cell behaviour in CNF and Matrigel cultures. Both cell lines formed compact spheroids in CNF but loose cell aggregates in Matrigel. Interestingly, the type of cell adhesion protein, and not the bond strength, appeared to be a key factor in the formation of compact spheroids. The gene expression of E- and N-cadherins, proteins on cell membrane responsible for cell-cell interactions, was increased in CNF culture, leading to formation of compact spheroids while Matrigel culture induced integrin-laminin binding and downregulated E-cadherin expression, resulting in looser cell aggregates. These findings enhance our understanding of cell-biomaterial interactions in 3D cultures and offer insights for improved 3D cell models, culture biomaterials, and applications in drug research.

The diazirine-mediated photo-crosslinking of collagen improves biomaterial mechanical properties and cellular interactions

In tissue engineering, crosslinking with carbodiimides such as EDC is omnipresent to improve the mechanical properties of biomaterials. However, in collagen biomaterials, EDC reacts with glutamate or aspartate residues, inactivating the binding sites for cellular receptors and rendering collagen inert to many cell types. In this work, we have developed a crosslinking method that ameliorates the rigidity, stability, and degradation rate of collagen biomaterials, whilst retaining key interactions between cells and the native collagen sequence. Our approach relies on the UV-triggered reaction of diazirine groups grafted on lysines, leaving critical amino acid residues intact. Notably, GxxGER recognition motifs for collagen-binding integrins, ablated by EDC crosslinking, were left unreacted, enabling cell attachment, spreading, and colonization on films and porous scaffolds. In addition, our procedure conserves the architecture of biomaterials, improves their resistance to collagenase and cellular contraction, and yields material stiffness akin to that obtained with EDC. Importantly, diazirine-crosslinked collagen can host mesenchymal stem cells, highlighting its strong potential as a substrate for tissue repair. We have therefore established a new crosslinking strategy to modulate the mechanical features of collagen porous scaffolds without altering its biological properties, thereby offering an advantageous alternative to carbodiimide treatment. Statement of significanceThis article describes an approach to improve the mechanical properties of collagen porous scaffolds, without impacting collagen's natural interactions with cells. This is significant because collagen crosslinking is overwhelmingly performed using carbodiimides, which results in a critical loss of cellular affinity. By contrast, our method leaves key cellular binding sites in the collagen sequence intact, enabling cell-biomaterial interactions. It relies on the fast, UV-triggered reaction of diazirine with collagen, and does not produce toxic by-products. It also supports the culture of mesenchymal stem cells, a pivotal cell type in a wide range of tissue repair applications. Overall, our approach offers an attractive option for the crosslinking of collagen, a prominent material in the growing field of tissue engineering.

Supramolecular Hydrogel with Ultra-Rapid Cell-Mediated Network Adaptation for Enhancing Cellular Metabolic Energetics and Tissue Regeneration.

Cellular energetics plays an important role in tissue regeneration, and the enhanced metabolic activity of delivered stem cells can accelerate tissue repair and regeneration. However, conventional hydrogels with limited network cell adaptability restrict cell-cell interactions and cell metabolic activities. In this work, it is shown that a cell-adaptable hydrogel with high network dynamics enhances the glucose uptake and fatty acid β-oxidation of encapsulated human mesenchymal stem cells (hMSCs) compared with a hydrogel with low network dynamics. It is further shown that the hMSCs encapsulated in the high dynamic hydrogels exhibit increased tricarboxylic acid (TCA)cycle activity, oxidative phosphorylation (OXPHOS), and adenosine triphosphate (ATP) biosynthesis via an E-cadherin- and AMP-activated protein kinase (AMPK)-dependent mechanism. The in vivo evaluation further showed that the delivery of MSCs by the dynamic hydrogel enhanced in situ bone regeneration in an animal model. It is believed that the findings provide critical insights into the impact of stem cell-biomaterial interactions on cellular metabolic energetics and the underlying mechanisms.

Enhancing biomedical applications: Modifying porous poly-di-methyl-siloxane (PDMS) structures with magnetite nanoparticles (MNPs) to improve interaction with normal human breast cells (MCF10A cells)

The phenomenon of cell-biomaterial interaction is responsible for adherent cells' adhesion to the biomaterial surface and the corresponding cell activities. The study aimed to enhance biocompatibility and versatility by modification of porous PDMS structures with MNPs for their safe interaction with normal human breast cells, MCF10A cell line. Preparation of the MNP-modified porous PDMS substrate was carried out by mixing a silicone elastomer base with a curing agent at a specific ratio, typically in a 10:1, followed by modification with MNP and the creation of pores of different dimensions. The substrate was subsequently characterized with Fourier-transform infrared spectroscopy. Furthermore, the assessment of cell proliferation and fluorescence imaging was done using the Alamar blue assay and fluorescence microscopy, respectively. The result of the study showed that PDMS + MNP (non-porous) did not significantly differ in percentage Alamar blue reduction at 4 hours when compared to PDMS + MNP_0-150, PDMS + MNP_150-250, and PDMS + MNP_250-500. Additionally, all the groups differed significantly (P>0.05) from one another at 48 and 96 h, except the PDMS+MNP_150-250 group compared to the PDMS+MNP_250-500 group, which did not exhibit any significant differences (P>0.05). The result further showed that when compared to all other groups, the fluorescence imaging result revealed that, after 96 h, there was very little cell attachment and proliferation on the surface of PDMS+MNP (non-porous). Other groups demonstrated discernable cell adhesion and proliferation over time. These outcomes demonstrate the significance of porosity in influencing cellular interactions and highlight its role in cell proliferation on biomaterial.

The future of cell-instructive biomaterials for tissue regeneration–a perspective from early career clinician-scientists

Cell-instructive biomaterials are an essential component in tissue engineering and regenerative medicine. In the past three decades since the term “Tissue Engineering” was coined, researchers have made significant progress towards regenerating disease or damage tissues and organs by combining innovations in biomaterials, signaling molecules and cell therapies. However, challenges persist including limitations in properties of cell-instructive biomaterials, lack of advanced manufacturing technologies for precise spatiotemporal control of key players in tissue engineering, and hurdles in clinical translation and regulatory process. In this perspective article, we briefly review the current state of the field including the evolution in our understanding of the role biomaterial mechanics and scaffolding architecture, development of self-healing and modular biomaterials, and progress in advanced manufacturing technologies such as 3D bioprinting. In addition, we discuss about how innovation in research technologies including multi-omics and spatial biology, and advanced imaging modalities may pave the way for enhancing our understanding about cell-biomaterial interactions. Finally, we present our perspective as early career clinicians and researchers on the key role and potential impact that clinician-scientists can generate in the development, validation, clinical translation and adoption of the next-generation of cell-instructive biomaterials for application in engineering tissues and organs to impact human health.

Pristine gelatin incorporation as a strategy to enhance the biofunctionality of poly(vinyl alcohol)-based hydrogels for tissue engineering applications.

Synthetic polymers, such as poly(vinyl alcohol) (PVA), are popular biomaterials for the fabrication of hydrogels for tissue engineering and regenerative medicine (TERM) applications, as they provide excellent control over the physico-chemical properties of the hydrogel. However, their bioinert nature is known to limit cell-biomaterial interactions by hindering cell infiltration, blood vessel recruitment and potentially limiting their integration with the host tissue. Efforts in the field have therefore focused on increasing the biofunctionality of synthetic hydrogels, without limiting the advantages associated with their tailorability and controlled release capacity. The aim of this study was to investigate the suitability of pristine gelatin to enhance the biofunctionality of tyraminated PVA (PVA-Tyr) hydrogels, by promoting cell infiltration and host blood vessel recruitment for TERM applications. Pure PVA-Tyr hydrogels and PVA-Tyr hydrogels incorporated with vascular endothelial growth factor (VEGF), a well-known pro-angiogenic stimulus, were used for comparison. Incorporating increasing concentrations of VEGF (0.01-10 μg mL-1) or gelatin (0.01-5 wt%) did not influence the physical properties of PVA-Tyr hydrogels. However, their presence within the polymer network (>0.1 μg mL-1 VEGF and >0.1 wt% gelatin) promoted endothelial cell interactions with the hydrogels. The covalent binding of unmodified gelatin or VEGF to the PVA-Tyr network did not hamper their inherent bioactivity, as they both promoted angiogenesis in a chick chorioallantoic membrane (CAM) assay, performing comparably with the unbound VEGF control. When the PVA-Tyr hydrogels were implanted subcutaneously in mice, it was observed that cell infiltration into the hydrogels was possible in the absence of gelatin or VEGF at 1- or 3-weeks post-implantation, highlighting a clear difference between in vitro an in vivo cell-biomaterial interaction. Nevertheless, the presence of gelatin or VEGF was necessary to enhance blood vessel recruitment and infiltration, although no significant difference was observed between these two biological molecules. Overall, this study highlights the potential of gelatin as a standalone pro-angiogenic cue to enhance biofunctionality of synthetic hydrogels and provides promise for their use in a variety of TERM applications.

Decellularization of caprine forestomach rumen tissue modified with silver nanowires as an antibacterial skin substitute scaffold in wound care therapeutics.

In this study, caprine forestomach native collagen (CFNC) isolated from rumen tissues is reported for the first time with subsequent surface modifications with varying concentrations of silver nanowires (AgNWs). Accordingly, CFNC/AgNWs scaffolds were prepared to be used as suitable wound healing dressing materials through a sequential isolation and decellularization process, followed by step-wise AgNW surface modification and ultraviolet (UV) crosslinking. The significant outcomes of this research highlight that CFNC/AgNWs scaffolds exhibit a highly porous three-dimensional (3D) network structure with favourable physicochemical characteristics. Also, the comprehensive tensile testing demonstrated that there were changes in mechanical properties based on the AgNW content. The CFNC/AgNWs scaffolds also exhibited strong antibacterial action against E. coli and S. aureus in a dose-dependent manner. The release of Ag+ ions from CFNC/AgNWs scaffolds exhibited a slow and sustained release pattern over an extended period of time. The cell-biomaterial interaction studies on CFNC/AgNWs scaffolds using L929 fibroblast cells showed dose-dependent and time-dependent toxicity when the concentration exceeded above 1 mg mL-1. The cytotoxicity is mainly due to the higher concentration of Ag+ ions which initiates cell death through lipid peroxidation and causes cell membrane damage. The biocompatibility test results serve as a reference point to select the optimal dosage of AgNWs with balanced antibacterial and biocompatibility properties. Thus, the developed CFNC/AgNWs scaffolds will serve as a versatile wound dressing material similar to other metallic or conjugated reconstituted collagen systems with the added benefit of strong antimicrobial properties, and as a biomimetic xenograft for skin regeneration.

Adjusting to Your Surroundings: An Inquiry-Based Learning Module to Teach Principles of Mechanobiology for Regenerative Medicine

Mechanobiology is an interdisciplinary field that aims to understand how physical forces impact biological systems. Enhancing our knowledge of mechanobiology has become increasingly important for understanding human disease and developing novel therapeutics. There is a societal need to teach diverse students principles of mechanobiology so that we may collectively expand our knowledge of this subject and apply new principles to improving human health. Toward this goal, we designed, implemented, and evaluated a hands-on, inquiry-based learning (IBL) module to teach students principles of cell–biomaterial interactions. This module was designed to be hosted in two 3-h sessions, over two consecutive days. During this time, students learned how to synthesize and mechanically test biomaterials, culture bacteria cells, and assess effects of matrix stiffness on bacteria cell proliferation. Among the 73 students who registered to participate in our IBL mechanobiology module, 40 students completed both days and participated in this study. A vast majority of the participants were considered underrepresented minority (URM) students based on race/ethnicity. Using pre/post-tests, we found that students experienced significant learning gains of 33 percentage points from completing our IBL mechanobiology module. In addition to gaining knowledge of mechanobiology, validated pre/post-surveys showed that students also experienced significant improvements in scientific literacy. Instructors may use this module as described, increase the complexity for an undergraduate classroom assignment, or make the module less complex for K-12 outreach. As presented, this IBL mechanobiology module effectively teaches diverse students principles of mechanobiology and scientific inquiry. Deploying this module, and similar IBL modules, may help advance the next generation of mechanobiologists.

Ascorbic Acid Enhances the Metabolic Activity, Growth and Collagen Production of Human Dermal Fibroblasts Growing in Three-dimensional (3D) Culture

Tissue engineering (TE) enables the development of functional synthetic substitutes to be replaced with damaged tissues and organs instead of the use of auto or allografts. A wide range of biomaterials is currently in use as TE scaffolds. Among these materials, naturally sourced ones are favorable due to being highly biocompatible and supporting cell growth and function, whereas synthetic ones are advantageous because of the high tunability on mechanical and physical properties as well as being easy to process. Alongside the advantages of synthetic polymers, they mostly show hydrophobic behavior that limits biomaterial-cell interaction and, consequently, the functioning of the developed TE constructs. In this study, we assessed the impact of L-Ascorbic acid 2-phosphate (AA2P) on improving the culture conditions of human dermal fibroblasts (HDFs) growing on a three-dimensional (3D) scaffold made of polycaprolactone (PCL) using emulsion templating. Our results demonstrated that AA2P enhances the metabolic activity and growth of HDFs as well as collagen deposition by them when supplemented in their growth medium at 50 µg/mL concentration. It showed a great potential to be used as a growth medium supplement to circumvent the disadvantages of culturing human cells on a synthetic biomaterial that is not favored in default. AA2P's potential to improve cell growth and collagen deposition may prove an effective way to culture human cells on 3D PCL PolyHIPE scaffolds for various TE applications.

Double‐Orthogonal Gradient‐Based High‐Throughput Screening Platform for Studying Cell Response Toward Combined Physicochemical Biomaterial Properties

Implant‐associated complications arise due to non‐optimized cell–biomaterial interactions. It is well known that cells respond to their physicochemical microenvironment on 2D interfaces and 3D networks. Attempts to manipulate this interaction target surface parameters such as wettability (W), stiffness (S), and topography (T) to influence cell differentiation, adhesion, and morphology, due to induction of gene activation and protein expression. Investigating the combinatorial influence of all three mentioned parameters simultaneously remains challenging, though most realistic, since all three parameters are inherently present on a surface. Herein, a novel high‐throughput screening technology, which allows investigating the cell response of human bone‐marrow‐derived mesenchymal stem cells toward three varying biomaterial surface parameters simultaneously, is presented. The platform provides efficient screening and cell response readout to a vast amount of combined biomaterial surface properties, in a single‐cell experiment. Surface gradients of aligned wrinkle T, S, and W are orthogonally combined giving four combinatorial surfaces. The screening outcome is validated by translating interesting regions to homogeneous surfaces. Cells are found to behave similar to the screening in terms of adhesion, spreading, and vimentin expression. The technology tremendously supports the identification of optimal surface parameter combinations and potentially addressing many of the current implant‐associated complications.

Biodegradable Cardiac Occluder with Surface Modification by Gelatin-Peptide Conjugate to Promote Endogenous Tissue Regeneration.

Transcatheter intervention has been the preferred treatment for congenital structural heart diseases by implanting occluders into the heart defect site through minimally invasive access. Biodegradable polymers provide a promising alternative for cardiovascular implants by conferring therapeutic function and eliminating long-term complications, but inducing in situ cardiac tissue regeneration remains a substantial clinical challenge. PGAG (polydioxanone/poly (l-lactic acid)-gelatin-A5G81) occluders are prepared by covalently conjugating biomolecules composed of gelatin and layer adhesive protein-derived peptides (A5G81) to the surface of polydioxanone and poly (l-lactic acid) fibers. The polymer microfiber-biomacromolecule-peptide frame with biophysical and biochemical cues could orchestrate the biomaterial-host cell interactions, by recruiting endogenous endothelial cells, promoting their adhesion and proliferation, and polarizing immune cells into anti-inflammatory phenotypes and augmenting the release of reparative cytokines. In a porcine atrial septal defect (ASD) model, PGAG occluders promote in situ tissue regeneration by accelerating surface endothelialization and regulating immune response, which mitigate inflammation and fibrosis formation, and facilitate the fusion of occluder with surrounding heart tissue. Collectively, this work highlights the modulation of cell-biomaterial interactions for tissue regeneration in cardiac defect models, ensuring endothelialization and extracellular matrix remodeling on polymeric scaffolds. Bioinspired cell-material interface offers a highly efficient and generalized approach for constructing bioactive coatings on medical devices.

Advances and Challenges in Cell Biology for Cultured Meat.

Cultured meat is an emerging biotechnology that aims to produce meat from animal cell culture, rather than from the raising and slaughtering of livestock, on environmental and animal welfare grounds. The detailed understanding and accurate manipulation of cell biology are critical to the design of cultured meat bioprocesses. Recent years have seen significant interest in this field, with numerous scientific and commercial breakthroughs. Nevertheless, these technologies remain at a nascent stage, and myriad challenges remain, spanning the entire bioprocess. From a cell biological perspective, these include the identification of suitable starting cell types, tuning of proliferation and differentiation conditions, and optimization of cell-biomaterial interactions to create nutritious, enticing foods. Here, we discuss the key advances and outstanding challenges in cultured meat, with a particular focus on cell biology, and argue that solving the remaining bottlenecks in a cost-effective, scalable fashion will require coordinated, concerted scientific efforts. Success will also require solutions to nonscientific challenges, including regulatory approval, consumer acceptance, and market feasibility. However, if these can be overcome, cultured meat technologies can revolutionize our approach to food.

Cell-Tissue Interaction: The Biomimetic Approach to Design Tissue Engineered Biomaterials.

The advancement achieved in Tissue Engineering is based on a careful and in-depth study of cell-tissue interactions. The choice of a specific biomaterial in Tissue Engineering is fundamental, as it represents an interface for adherent cells in the creation of a microenvironment suitable for cell growth and differentiation. The knowledge of the biochemical and biophysical properties of the extracellular matrix is a useful tool for the optimization of polymeric scaffolds. This review aims to analyse the chemical, physical, and biological parameters on which are possible to act in Tissue Engineering for the optimization of polymeric scaffolds and the most recent progress presented in this field, including the novelty in the modification of the scaffolds' bulk and surface from a chemical and physical point of view to improve cell-biomaterial interaction. Moreover, we underline how understanding the impact of scaffolds on cell fate is of paramount importance for the successful advancement of Tissue Engineering. Finally, we conclude by reporting the future perspectives in this field in continuous development.

Transcriptome Analysis of Human Vascular Smooth Muscle Cells Cultured on a Polyglycolic Acid Mesh Scaffold

To construct tissue-engineered blood vessels (TEBVs) in vitro, it is necessary to transfer seed cells to three-dimensional (3D) scaffolds for culture. However, what happens to the behavior of the cells after they are transferred to the scaffold is unclear. Therefore, in this study, a transcriptome analysis was used to characterize the differentially expressed genes (DEGs) of vascular smooth muscle cells (VSMCs) before and after transfer to 3D polyglycolic acid (PGA) scaffolds and to understand the changes in functional gene expression in the early stage of 3D culture. Transcriptome sequencing results showed that DEGs in the seed cells were mainly enriched in cell proliferation and cell-cell adhesion. The DEGs of cells grown in a 3D PGA scaffold (PGA-VSMCs) were mainly enriched in signal transduction. Furthermore, we found that ERK1/2 was significantly activated in PGA-VSMCs and inhibiting the phosphorylation level of ERK 1/2 in PGA-VSMCs significantly increased the expression of elastin. In conclusion, the PGA scaffold material altered gene expression in VSMCs and affected the elastin production. This study advances our understanding of biomaterial-cell interactions and provides valuable insights for improving the cultivation of TEBVs.

Assessing Biomaterial‐Induced Stem Cell Lineage Fate by Machine Learning‐Based Artificial Intelligence (Adv. Mater. 19/2023)

Stem Cell Lineage Fate Highly accurate, efficient, and convenient evaluation for biomaterial-induced stem cell lineage fate is pivotal for regenerative biomaterials research. In article number 2210637, Binbin Lai, Xuehui Zhang, Xuliang Deng, and co-workers report MeD-P, a machine-learning-supported intelligent evaluation model, for predicting human mesenchymal stem cell–biomaterial interaction based on RNA-seq data. This framework shows the potential of artificial intelligence in facilitating biological performance optimization of biomaterials in stem cell lineage fate regulation.