Figure - available from: Communications Biology
This content is subject to copyright. Terms and conditions apply.
Differentiation of HUVECs using synthetic glycosaminoglycans
A Schematic representation of the mixture of the synthetic glycosaminoglycans and growth factors (FGF2) with an elastin-like recombinamer (ELR) to give functionalized hydrogels. Synthetic glycosaminoglycans were conjugated to the ELR through ’click chemistry’. HUVEC cells were added on top and allowed to differentiate for 24 h. B Undifferentiated HUVECs when cultured in medium without supplements, characterized by cells clumping together and dying. C Differentiated HUVECs when stimulated with complete medium, characterized by the formation of tube-like structures (highlighted with white arrows). D, E Undifferentiated cells when stimulated with only FGF2 or only synthetic glycosaminoglycans. F Differentiated cells when stimulated with the combination of synthetic glycosaminoglycans and FGF2, (tube-like structures highlighted with white arrows).

Differentiation of HUVECs using synthetic glycosaminoglycans A Schematic representation of the mixture of the synthetic glycosaminoglycans and growth factors (FGF2) with an elastin-like recombinamer (ELR) to give functionalized hydrogels. Synthetic glycosaminoglycans were conjugated to the ELR through ’click chemistry’. HUVEC cells were added on top and allowed to differentiate for 24 h. B Undifferentiated HUVECs when cultured in medium without supplements, characterized by cells clumping together and dying. C Differentiated HUVECs when stimulated with complete medium, characterized by the formation of tube-like structures (highlighted with white arrows). D, E Undifferentiated cells when stimulated with only FGF2 or only synthetic glycosaminoglycans. F Differentiated cells when stimulated with the combination of synthetic glycosaminoglycans and FGF2, (tube-like structures highlighted with white arrows).

Source publication
Article
Full-text available
Healthy regeneration of tissue relies on a well-orchestrated release of growth factors. Herein, we show the use of synthetic glycosaminoglycans for controlled binding and release of growth factors to induce a desired cellular response. First, we screened glycosaminoglycans with growth factors of interest to determine kon (association rate constant)...

Similar publications

Article
Full-text available
The development of vascularized tissue is a substantial challenge within the field of tissue engineering and regenerative medicine. Studies have shown that positively-charged microspheres exhibit dual-functions: (1) facilitation of vascularization and (2) controlled release of bioactive compounds. In this study, gelatin-coated microspheres were pro...

Citations

... The high-affinity leptin receptor (LEPR)-binding peptide in the collagen scaffold hugely enhanced endogenous mesenchymal cell recruitment and regeneration of damaged lung tissue. Glycosaminoglycans are the main component of the ECM and could contribute to the recruitment of immune and vascular cells, inducing potent and localized growth factors to initiate tissue regeneration [121]. Numerous molecules, such as collagen, gelatin, and alginate, have been used in tissue engineering to mimic native ECM scaffolds. ...
Article
Full-text available
Lung organoids display a tissue-specific functional phenomenon and mimic the features of the original organ. They can reflect the properties of the cells, such as morphology, polarity, proliferation rate, gene expression, and genomic profile. Alveolar type 2 (AT2) cells have a stem cell potential in the adult lung. They produce and secrete pulmonary surfactant and proliferate to restore the epithelium after damage. Therefore, AT2 cells are used to generate alveolar organoids and can recapitulate distal lung structures. Also, AT2 cells in human-induced pluripotent stem cell (iPSC)-)-derived alveolospheres express surfactant proteins and other factors, indicating their application as suitable models for studying cell–cell interactions. Recently, they have been utilized to define mechanisms of disease development, such as COVID-19, lung cancer, idiopathic pulmonary fibrosis, and chronic obstructive pulmonary disease. In this review, we show lung organoid applications in various pulmonary diseases, drug screening, and personalized medicine. In addition, stem cell-based therapeutics and approaches relevant to lung repair were highlighted. We also described the signaling pathways and epigenetic regulation of lung regeneration. It is critical to identify novel regulators of alveolar organoid generations to promote lung repair in pulmonary diseases.
... The combination of SCM with fibrin from the PRP enables the slow release of growth factors and strengthens the fibrin structure as a scaffold [36,37]. The fibrin content of the PRP provided stronger matrix networks, slowed down the degradation rate of the SCM, controlled the gradual release of growth factors, and generated the constant supply of growth factors to cells [38][39][40]. In addition, cell viability is affected by calcium ions released from the SCM during degradation. ...
Article
Full-text available
To solve problems in using natural sea corals with high biocompatibility, good osteoconductivity, and ideal degradability, a synthetic three-dimensional coral matrix was fabricated and observed for its capability to enhance osteogenic differentiation of human mesenchymal stem cells (h-MSCs), in the presence or absence of growth factors (GFs) supplied from platelet-rich plasma (PRP). Expressions of runx, osterix, and osteocalcin were investigated, following cell attachment, and proliferation analysis. Ectopic bone formation in nonosseous tissues of Sprague-Dawley rats at predetermined time intervals was investigated, including mineralized tissue growth in vivo. The 3D synthetic coral matrix (SCM) can interact with the GF cocktail in the PRP and MSCs to generate and secret bone extracellular matrix (ECM) both in vitro and in vivo. The matrix supplied with GF cocktail from the PRP provided an ideal microenvironment for MSCs to attach, proliferate, and differentiate into osteoblast faster, as indicated by the expression levels of runx2, osterix, and osteocalcin. The high capability of SCMs to enhance bone formation has been proven by the formation of ectopic bones in the nonosseous environment. The incorporated PRP provided blood proteins such as fibrin to slow down matrix degradation, whereas GF supplied by the PRP stimulated h-MSCs to attach and proliferate onto the matrix. Moreover, the GF supplied by the PRP enhanced osteogenic differentiation and mineralization, accelerating bone regeneration. Valorization phases are needed to apply the SCM for bone tissue engineering in clinics. HIGHLIGHTS A synthetic coral matrix (SCM) with ideal macro- and microstructural appearance and physical and chemical properties, with tunable platelet-rich plasma (PRP)-loading capacity and release manner, was successfully fabricated The matrix provided an ideal microenvironment for human mesenchymal stem cells (h-MSCs) to attach, proliferate, and differentiate into osteoblasts indicated by high expression levels of bone regeneration markers The high capability of SCM to enhance bone regeneration has been validated by the formation of ectopic bones in the nonosseous environment of subcutaneous rat dorsal tissues The incorporation of a growth factor cocktail from the PRP did not alter the results in the matrix without growth factors, which act as signaling molecules The SCM was found to degrade faster in the group without h-MSCs, indicating that the system with cells promoted faster bone formation GRAPHICAL ABSTRACT
... The adoption of carriers resolves the limitations inherent in cytokine-based therapies. Carriers obviate the need for frequent administration of rapidly inactivated growth factors, thus enabling a reduction in the cumulative daily dose and mitigating potential adverse effects [37]. Our study employed Ligasano (a commercial dressing) as the base for cytokine loading. ...
Article
Full-text available
Wounds represent a common occurrence in human life. Consequently, scientific investi- gations are underway to advance wound healing methodologies, with a notable focus on dressings imbued with biologically active compounds capable of orchestrating the wound microenvironment through meticulously regulated release mechanisms. Among these bioactive agents are cytokines, which, when administered to the wound milieu without appropriate protection, undergo rapid loss of their functional attributes. Within the context of this research, we present a method for fabricating dressings enriched with G-CSF (granulocyte colony-stimulating factor) or GM-CSF (granulocyte- macrophage colony-stimulating factor), showcasing both biological activity and protracted release dynamics. Based on Ligasano, a commercial polyurethane foam dressing, and chitosan crosslinked with TPP (sodium tripolyphosphate), these dressings are noncytotoxic and enable cytokine incorpora- tion. The recovery of cytokines from dressings varied based on the dressing preparation and storage techniques (without modification, drying, freeze-drying followed by storage at 4 ◦C or freeze-drying followed by storage at 24 ◦C) and cytokine type. Generally, drying reduced cytokine levels and their bioactivity, especially with G-CSF. The recovery of G-CSF from unmodified dressings was lower compared to GM-CSF (60% vs. 80%). In summary, our freeze-drying approach enables the storage of G-CSF or GM-CSF enriched dressings at 24 ◦C with minimal cytokine loss, preserving their biological activity and thus enhancing future clinical availability.
... In response to nanofibrous scaffolds with recombinant human epidermal growth factor (rhEGF), faster wound closure rates were observed compared to murine excisional wounds without rhEGF [56,59]. Several studies have shown that basic fibroblast growth factor (bFGF) promotes cell proliferation, accelerated wound contraction, neovascularization, and enhanced re-epithelialization with robust granulation tissue formation [60][61][62]. Soderlund et al. [63] demonstrated that synthetic glycosaminoglycans could release bFGF slowly, resulting in minimized FBR and a higher ratio of M2:M1 macrophages, altering the immunomodulatory capabilities of growth factor-releasing biomaterials. ...
Article
Full-text available
Implantable biomaterials represent the forefront of regenerative medicine, providing platforms and vessels for delivering a creative range of therapeutic benefits in diverse disease contexts. However, the chronic damage resulting from implant rejection tends to outweigh the intended healing benefits, presenting a considerable challenge when implementing treatment-based biomaterials. In response to implant rejection, proinflammatory macrophages and activated fibroblasts contribute to a synergistically destructive process of uncontrolled inflammation and excessive fibrosis. Understanding the complex biomaterial–host cell interactions that occur within the tissue microenvironment is crucial for the development of therapeutic biomaterials that promote tissue integration and minimize the foreign body response. Recent modifications of specific material properties enhance the immunomodulatory capabilities of the biomaterial and actively aid in taming the immune response by tuning interactions with the surrounding microenvironment either directly or indirectly. By incorporating modifications that amplify anti-inflammatory and pro-regenerative mechanisms, biomaterials can be optimized to maximize their healing benefits in harmony with the host immune system.
Article
Full-text available
Glycosaminoglycans (GAGs) play a crucial role in tissue homeostasis by regulating the activity and diffusion of bioactive molecules. Incorporating GAGs into biomaterials has emerged as a widely adopted strategy in medical applications, owing to their biocompatibility and ability to control the release of bioactive molecules. Nevertheless, immobilized GAGs on biomaterials can elicit distinct cellular responses compared to their soluble forms, underscoring the need to understand the interactions between GAG and bioactive molecules within engineered functional biomaterials. By controlling critical parameters such as GAG type, density, and sulfation, it becomes possible to precisely delineate GAG functions within a biomaterial context and to better mimic specific tissue properties, enabling tailored design of GAG‐based biomaterials for specific medical applications. However, this requires access to pure and well‐characterized GAG compounds, which remains challenging. This review focuses on different strategies for producing well‐defined GAGs and explores high‐throughput approaches employed to investigate GAG–growth factor interactions and to quantify cellular responses on GAG‐based biomaterials. These automated methods hold considerable promise for improving our understanding of the diverse functions of GAGs. In perspectives; we encourage the scientific community to adopt a rational approach in designing GAG‐based biomaterials, taking into account the in vivo properties of the targeted tissue for medical applications.)) This article is protected by copyright. All rights reserved