Silk fibroin (SF) is a natural fibrous polymer with strong potential for many biomedical applications. SF has attracted interest in the field of bone tissue engineering due to its extraordinary ...characteristics in terms of elasticity, flexibility, biocompatibility and biodegradability. However, low osteogenic capacity has limited applications for SF in the orthopedic arena unless suitably functionalized. Hydroxyapatite (HAp) is a well-established bioceramic with biocompatibility and appropriate for constructing orthopedic and dental substitutes. However, HAp ceramics tend to be brittle which can restrict applications in the repair of load-bearing tissues such as bones. Therefore, blending SF and HAp combines the useful properties of both materials as bone constructs for tissue engineering, the subject of this review.
We report on a simple carbohydrate amphiphile able to self-assemble into nanofibers upon enzymatic dephosphorylation. The self-assembly can be triggered by alkaline phosphatase (ALP) in solution or ...in situ by the ALP produced by osteosarcoma cell line, SaOs2. In the latter case, assembly and localized gelation occurs mainly on the cell surface. The gelation of the pericellular environment induces a reduction of the SaOs2 metabolic activity at an initial stage (≤7 h) that results in cell death at longer exposure periods (≥24 h). We show that this effect depends on the phosphatase concentration, and thus, it is cell-selective with prechondrocytes ATDC5 (that express ∼15-20 times lower ALP activity compared to SaOs2) not being affected at concentrations ≤1 mM. These results demonstrate that simple carbohydrate derivatives can be used in an antiosteosarcoma strategy with limited impact on the surrounding healthy cells/tissues.
Growth factors (GFs) are proteins secreted by cells that regulate a variety of biological processes. Although they have long been proposed as potent therapeutic agents, their administration in a ...soluble form has proven costly and ineffective due to their short half‐lives in biological environments. Biomaterial‐based approaches are increasingly sought as alternatives to improve the efficacy or, ideally, replace the need for exogenous administration of GFs in regenerative medicine strategies. The means by which these systems evolve from biomaterials for conventional controlled release of GFs to the recent extracellular matrix (ECM)–inspired approaches for sequestering these labile molecules and regulating their spatiotemporal activity and presentation are reviewed. Focus is placed on biomaterials functionalized either with ECM components, which show promiscuous GF binding, or with targeted GF ligands (antibodies, aptamers, or peptides). The potential of synthetic platforms with abiotic affinity as cost‐effective alternatives to the current biological ligands is also discussed. Overall, the various GF sequestering systems developed so far have remarkably improved the activity of GFs at reduced doses and, in some cases, completely avoided the need for their exogenous administration to guide cell fates. These bioinspired concepts thus enable the rational exploration of the full therapeutic potential of GFs in regenerative medicine.
Biomaterials for sequestration of growth factors are increasingly sought as alternatives to improve their efficacy or replace their exogenous administration in therapies. Recent extracellular matrix (ECM)‐inspired approaches, particularly functionalization with promiscuous ECM components or with targeted antibodies, aptamers, or peptides, are reviewed. Some of the most representative works are highlighted, and near future perspectives for the field are outlined.
In this work, carbon nanofibers were used as doping material to develop a highly conductive chitosan-based composite. Scaffolds based on chitosan only and chitosan/carbon composites were prepared by ...precipitation. Carbon nanofibers were homogeneously dispersed throughout the chitosan matrix, and the composite scaffold was highly porous with fully interconnected pores. Chitosan/carbon scaffolds had an elastic modulus of 28.1 ± 3.3 KPa, similar to that measured for rat myocardium, and excellent electrical properties, with a conductivity of 0.25 ± 0.09 S/m. The scaffolds were seeded with neonatal rat heart cells and cultured for up to 14 days, without electrical stimulation. After 14 days of culture, the scaffold pores throughout the construct volume were filled with cells. The metabolic activity of cells in chitosan/carbon constructs was significantly higher as compared to cells in chitosan scaffolds. The incorporation of carbon nanofibers also led to increased expression of cardiac-specific genes involved in muscle contraction and electrical coupling. This study demonstrates that the incorporation of carbon nanofibers into porous chitosan scaffolds improved the properties of cardiac tissue constructs, presumably through enhanced transmission of electrical signals between the cells.
Cancer is a leading cause of mortality and morbidity worldwide. Around 90% of deaths are caused by metastasis and just 10% by primary tumor. The advancement of treatment approaches is not at the same ...rhythm of the disease; making cancer a focal target of biomedical research. To enhance the understanding and prompts the therapeutic delivery; concepts of tissue engineering are applied in the development of in vitro models that can bridge between 2D cell culture and animal models, mimicking tissue microenvironment. Tumor spheroid represents highly suitable 3D organoid-like framework elucidating the intra and inter cellular signaling of cancer, like that formed in physiological niche. However, spheroids are of limited value in studying critical biological phenomenon such as tumor-stroma interactions involving extra cellular matrix or immune system. Therefore, a compelling need of tailoring spheroid technologies with physiologically relevant biomaterials or in silico models, is ever emerging. The diagnostic and prognostic role of spheroids rearrangements within biomaterials or microfluidic channel is indicative of patient management; particularly for the decision of targeted therapy. Fragmented information on available in vitro spheroid models and lack of critical analysis on transformation aspects of these strategies; pushes the urge to comprehensively overview the recent technological advancements (e.g. bioprinting, micro-fluidic technologies or use of biomaterials to attain the third dimension) in the shed of translationable cancer research. In present article, relationships between current models and their possible exploitation in clinical success is explored with the highlight of existing challenges in defining therapeutic targets and screening of drug efficacy.
Growth factors (GFs) are biomolecules with potent biological effects but inherent limitations hinder their potential as therapeutic agents and cell culture supplements in tissue engineering and ...regenerative medicine (TERM). Biomaterials that sequester endogenous GFs by affinity binding might circumvent such limitations and thus are being increasingly investigated. Here, molecularly imprinted nanoparticles (MINPs) are proposed as specific abiotic ligands for GFs. As a proof of concept, a conformational epitope of transforming growth factor‐β3 (TGF‐β3) is designed and surface imprinted onto polyacrylamide‐based nanoparticles by inverse microemulsion polymerization. It is found that, depending on the polymerization mixture composition, MINPs can recognize and preferentially bind TGF‐β3, either in noncompetitive assays or from a complex human fluid (platelet lysate). Substrates functionalized with MINPs are then used for 2D culture of adipose‐derived stem cells. Remarkably, gene and protein expression profiles show a marked upregulation of SOX‐9, suggesting activation of TGF‐β3 signaling pathways without requiring supplementation with exogenous GF. Likewise, culturing these cells in pellets incorporating MINPs previously incubated with platelet lysate results in higher collagen II‐rich matrix deposition, compared to pellets incorporating non‐imprinted nanoparticles. In summary, results suggest MINPs can be used as cost‐effective, stable, and scalable alternative abiotic GF ligands to guide cell fate in TERM applications.
A conformational epitope of transforming growth factor‐β3 (TGF‐β3) is designed and molecularly imprinted on nanoparticles via inverse microemulsion polymerization. Imprinted nanoparticles are shown to selectively bind and retain TGF‐β3 from complex mixtures. This ability is explored to elicit specific biological effects and direct stem cell fate without the addition of exogenous recombinant growth factors, in both 2D and 3D cultures.
Light guiding and manipulation in photonics have become ubiquitous in events ranging from everyday communications to complex robotics and nanomedicine. The speed and sensitivity of light–matter ...interactions offer unprecedented advantages in biomedical optics, data transmission, photomedicine, and detection of multi‐scale phenomena. Recently, hydrogels have emerged as a promising candidate for interfacing photonics and bioengineering by combining their light‐guiding properties with live tissue compatibility in optical, chemical, physiological, and mechanical dimensions. Herein, the latest progress over hydrogel photonics and its applications in guidance and manipulation of light is reviewed. Physics of guiding light through hydrogels and living tissues, and existing technical challenges in translating these tools into biomedical settings are discussed. A comprehensive and thorough overview of materials, fabrication protocols, and design architectures used in hydrogel photonics is provided. Finally, recent examples of applying structures such as hydrogel optical fibers, living photonic constructs, and their use as light‐driven hydrogel robots, photomedicine tools, and organ‐on‐a‐chip models are described. By providing a critical and selective evaluation of the field's status, this work sets a foundation for the next generation of hydrogel photonic research.
The current panorama of hydrogel‐based photonics and advances in fabrication techniques toward functional optical architectures are reviewed, evaluating their capabilities in the biomedical field. Further, the future potential for hydrogel photonic constructs to integrate into live tissues, advanced biosensing platforms, microrobotics, photomedicine, and lab‐on‐chip technologies are discussed.
Tissue engineering (TE) is continuously evolving assimilating inputs from adjacent scientific areas and their technological advances, including nanotechnology developments that have been spawning the ...range of available options for the precise manipulation and control of cells and cellular environments. Simultaneously, with the maturation of the field, TE has a growing and marked impact in other fields, such as cancer and other diseases research, enabling tri-dimensional (3D) tumor/tissue models of increased complexity that more closely resemble living tissue dynamics, playing a decisive role in the development of new and improved therapies. Nevertheless, TE is still struggling with translational issues. On this matter, the advent of personalized and precision medicine has opened new perspectives, particularly with the striking evolutions enabled by 3D bioprinting technologies. Based on a modified methodology grounded in the past years' approach, we have identified and reviewed some of the most high-impact publications on the topics that are revolutionizing TE and helping to define the future directions of the field, namely: (1) New trends in TE: Personalized/precision regenerative medicine and 3D bioprinting, (2) Contributions of TE to other fields: microfabricated tissue-engineered 3D models for cancer and other diseases research, and (3) Diagnostic and theranostic tools: monitoring and real-time control of TE systems.
Abstract Tissue engineering using scaffold-cell constructs holds the potential to develop functional strategies to regenerate bone. The interface of orthopedic implants with the host tissues is of ...great importance for its later performance. Thus, the optimization of the implant surface in a way that could stimulate osteogenic differentiation of mesenchymal stem cells (MSCs) is of significant therapeutic interest. The effect of surface roughness of polycaprolactone (PCL) on the osteogenic differentiation of human bone-marrow MSCs was investigated. We prepared surface roughness gradients of average roughness (Ra) varying from the sub-micron to the micrometer range (∼0.5–4.7 μm), and mean distance between peaks (RS m ) gradually varying from ∼214 μm to 33 μm. We analyzed the degree of cytoskeleton spreading, expression of alkaline phosphatase, collagen type 1 and mineralization. The response of cells to roughness divided the gradient into three groups of elicited stem cell behavior: 1) faster osteogenic commitment and strongest osteogenic expression; 2) slower osteogenic commitment but strong osteogenic expression, and 3) similar or inferior osteogenic potential in comparison to the control material. The stem-cell modulation by specific PCL roughness surfaces highlights the potential for creating effective solutions for orthopedic applications featuring a clinically relevant biodegradable material.
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