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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA · 2025 ·Vol. 122 ·期 13 ·e2416771122 · IF 9.1

Matrix degradation enhances stress relaxation, regulating cell adhesion and spreading

Badri Narayanan Narasimhan,Stephanie I. Fraley

In native extracellular matrices (ECM), cells utilize matrix metalloproteinases (MMPs) to degrade and remodel their microenvironment. Accordingly, synthetic matrices have been engineered to permit MMP-mediated cleavage, facilitating cell spreading, migration, and interactions. However, the interplay between matrix degradability and mechanical properties remains underexplored. We hypothesized that MMP activity induces immediate mechanical alterations in the ECM, which are subsequently detected by cells. We observed that both fibrillar collagen and synthetic degradable matrices exhibit enhanced stress relaxation following MMP exposure. Cells responded to these variations in relaxation by modulating their spreading and focal adhesions. Furthermore, we demonstrated that stress relaxation and cell spreading can be precisely controlled through the rational design of matrix degradability. These findings establish a fundamental link between matrix degradability and stress relaxation, with potential implications for a broad spectrum of biological applications.

CAS / MDL: 161552-03-0
研究领域: 生物材料学 · 细胞生物学 · 生物力学
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ACS Applied Materials & Interfaces · 2016 · IF 7.145

Controlling Gel Structure to Modulate Cell Adhesion and Spreading on the Surface of Microcapsules

Huizhen Zheng,Meng Gao,Ying Ren,Ruyun Lou,Hongguo Xie,Weiting Yu,Xiudong Liu,Xiaojun Ma

The surface properties of implanted materials or devices play critical roles in modulating cell behavior. However, the surface properties usually affect cell behaviors synergetically so that it is still difficult to separately investigate the influence of a single property on cell behavior in practical applications. In this study, alginate–chitosan (AC) microcapsules with a dense or loose gel structure were fabricated to understand the effect of gel structure on cell behavior. Cells preferentially adhered and spread on the loose gel structure microcapsules rather than on the dense ones. The two types of microcapsules exhibited nearly identical surface positive charges, roughness, stiffness, and hydrophilicity; thus, the result suggested that the gel structure was the principal factor affecting cell behavior. X-ray photoelectron spectroscopy analyses demonstrated that the overall percentage of positively charged amino groups was similar on both microcapsules. The different gel structures led to different states and distributions of the positively charged amino groups of chitosan, so we conclude that the loose gel structure facilitated greater cell adhesion and spreading mainly because more protonated amino groups remained unbound and exposed on the surface of these microcapsules.

研究领域: 生物材料学 · 细胞生物学
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Bio-Design and Manufacturing · 2022 ·Vol. 6 ·期 2 ·136-149 · IF 5.887

Functionalized alginate-based bioinks for microscale electrohydrodynamic bioprinting of living tissue constructs with improved cellular spreading and alignment

Qiu Zhennan,Zhu Hui,Wang Yutao,Kasimu Ayiguli,Li Dichen,He Jiankang

Bioprinting has been widely investigated for tissue engineering and regenerative medicine applications. However, it is still difficult to reconstruct the complex native cell arrangement due to the limited printing resolution of conventional bioprinting techniques such as extrusion- and inkjet-based printing. Recently, an electrohydrodynamic (EHD) bioprinting strategy was reported for the precise deposition of well-organized cell-laden constructs with microscale filament size, whereas few studies have been devoted to developing bioinks that can be applied for EHD bioprinting and simultaneously support cell spreading. This study describes functionalized alginate-based bioinks for microscale EHD bioprinting using peptide grafting and fibrin incorporation, which leads to high cell viability (>90%) and cell spreading. The printed filaments can be further refined to as small as 30 μm by incorporating polyoxyethylene and remained stable over one week when exposed to an aqueous environment. By utilizing the presented alginate-based bioinks, layer-specific cell alignment along the printing struts could be observed inside the EHD-printed microscale filaments, which allows fabricating living constructs with cell-scale filament resolution for guided cellular orientation. Graphic abstract

研究领域: 生物打印 · 组织工程 · 再生医学
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MATERIALS & DESIGN · 2024 · IF 7.6

Physically crosslinked poly(vinyl alcohol)-based hydrogels for cartilage tissue engineering

Changxin Xiang,Zijian Guo,Qing Zhang,Zehua Wang,Xiaona Li,Weiyi Chen,Xiaochun Wei,Pengcui Li,Chuan Xiang

Due to the limited self-healing ability of cartilage, cartilage defect repair remains a challenge in clinical treatment. Therefore, there is a need to provide patients with a promising cartilage defect repair strategy. In this study, we have reported an icariin-loaded PVA based biocompatible hydrogel scaffold for cartilage defect repair. The PTGH+Icariin hydrogel was prepared by a simple physical cross-linking method and consisted of polyvinyl alcohol (PVA), tannic acid (TA), gelatin (Gel), hyaluronic acid (HA) and icariin. Inspired by the natural cartilage matrix compositions, the Gel and HA were used to improve the bioactivity and biocompatibility of hydrogel. Furthermore, icariin was introduced to further enhance the hydrogel’s ability for cartilage regeneration. The results showed that PTGH+icariin hydrogel exhibited porous microstructures and tough mechanical properties. In vitro cell experiments confirmed PTGH+Icariin hydrogels could promote chondrocytes proliferation, chondrocytes spreading and chondrocytes migration. Meanwhile, the PTGH+Icariin hydrogel demonstrated the ability to promote the cartilage regeneration in a rat cartilage defect model. In particular, the implantation of PTGH+Icariin hydrogel could facilitate the restoration of motor function in rats. This study will provide a potential approach for the treatment of cartilage defects.

CAS / MDL: 9000-70-8 9002-89-5
研究领域: 组织工程 · 生物材料 · 生物医学工程 · 再生医学
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LANGMUIR · 2024 · IF 3.7

Integrin Subtypes and Lamellipodia Mediate Spatial Sensing of RGD Ligands during Cell Adhesion

Xiaokai Pan,Juan Nie,Jiacheng Lei,Peng Wang,Kaikai Zheng,Qiang Wei,Xiaojing Liu

Understanding how the spatial distribution of adhesive ligands regulates cell behavior is crucial for designing biomaterials. This study investigates how precisely controlled ligand spacing affects cell spreading and integrin subtype engagement. Using engineered polyacrylamide hydrogels with gold nanoparticle arrays, we explored the impact of RGD ligand spacings (30 and 150 nm) on human mesenchymal stromal cells. Cells exhibited distinct morphological behaviors: smaller spacings promoted larger spreading areas, while larger spacings resulted in elongated shapes with reduced spreading. Mechanistically, we found that the α5β1 integrin, not the αvβ3 integrin, played a central role in mediating these responses, alongside lamellipodia formation. Our findings provide critical insights into the spatial sensing of ligands, highlighting the influence of ligand spacing on cellular mechanotransduction and integrin-specific responses. This work advances the understanding of cell-material interactions and offers potential strategies for designing biomaterials to guide cell behavior in tissue engineering.

研究领域: 细胞生物学 · 生物材料科学 · 组织工程 · 生物物理学
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MACROMOLECULAR BIOSCIENCE · 2021 ·Vol. 21 ·期 11 ·2100189 · IF 4.979

Enzyme- and UV-Mediated Double-Network Hybrid Hydrogels for 3D Cell Culture application

Xiao-Pei Li,Lin Zou,Oluwatosin David Abodunrin,Xiao-Wei Wang,Ning-Ping Huang

Three-dimensional (3D) cell culture using hydrogel scaffolds can closely resemble the natural extracellular matrix (ECM), which offers appropriate mechanical support for cells and regulates cellular behavior. In this study, a bacterial transpeptidase sortase A (SA) is used to prepare enzymatically cross-linked methacrylated hyaluronic acid (HA) peptides (HAMA-P) hydrogel, which reveals fast gel kinetics under high SA cross-linking concentrations and can be used as an injection hydrogel for tissue repair or extrusive 3D bioprinting. Furthermore, methacrylated gelatin (GelMA) is introduced to build the hybrid hydrogel (HAMA-P-GelMA) with double cross-linking of enzyme-UV, which has shown proper physical properties (mechanical properties, swelling, degradation rate, etc.) of the hydrogel matrix, and displayed desirable effects on cell viability, adhesion, and cell spreading, when compared to GelMA or HAMA-P single-network hydrogels. The HAMA-P-GelMA hybrid hydrogels provide a favorable 3D milieu for cell growth and can be used as a 3D bio-ink or a carrier of stem cells/cytokines for injectable tissue repair and filling.

CAS / MDL: 760-93-0
研究领域: 生物医学工程 · 组织工程 · 材料科学 · 细胞生物学
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CARBOHYDRATE POLYMERS · 2022 · IF 10.723

Photocurable liquid crystal hydrogels with different chargeability and tunable viscoelasticity based on chitin whiskers

Jingsheng Chen,Zelin Zhu,Jiaqing Chen,Yiting Luo,Lin Li,Kun Liu,Shan Ding,Hong Li,Mingxian Liu,Changren Zhou,Binghong Luo

We develop a kind of photocurable liquid crystal hydrogels with bone extracellular matrix (ECM)-like liquid crystal state and viscoelasticity , as well as different chargeability. First, positively charged chitin whiskers (CHWs) and negatively charged maleic anhydride chitin whiskers (mCHWs) were prepared, which further self-assemble to form chiral nematic liquid crystals under ultrasonic treatment, respectively. Subsequently, poly (ethylene glycol) diacrylate (PEGDA) and photo initiator were added, and then two kinds of liquid crystal hydrogels with bone ECM-like viscoelasticity and different chargeability were prepared under ultraviolet (UV) irradiation. Benefiting from the bone ECM-like liquid crystal state and viscoelasticity, the prepared liquid crystal hydrogels exhibit remarkable cell affinity and osteogenic ability. Moreover, the liquid crystal hydrogel with negatively charged mCHWs is more favorable for cell adhesion , spreading and osteogenic differentiation than that with positively charged CHWs. This work provides a promising strategy to prepare the hydrogels with bone ECM-like liquid crystal properties and viscoelasticity for bone repair .

CAS / MDL: 1398-61-4
研究领域: 材料科学 · 生物材料 · 组织工程 · 生物医学工程
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CARBON · 2015 · IF 6.196

The preparation and characterization of polycaprolactone/graphene oxide biocomposite nanofiber scaffolds and their application for directing cell behaviors

Juqing Song,Huichang Gao,Guanglin Zhu,Xiaodong Cao,Xuetao Shi,Yingjun Wang

Biocomposite nanofiber scaffolds of polycaprolactone (PCL) with different graphene oxide (GO) concentrations were prepared using electrospinning technology. The successful incorporation of GO nanosheets into PCL polymer nanofibers improved the thermal and mechanical properties of the nanofibers because of the intrinsic properties developed due to the interactions of GO and PCL. In order to estimate the biocompatibility of PCL/GO composite scaffolds, mouse marrow mesenchymal stem cells (mMSCs) and low-differentiated rat pheochromocytoma (PC12-L) cells were cultured. Initial adhesion and spreading of the mMSCs and PC12-L cells on PCL/GO composite scaffolds with moderate addition of GO (0.3 and 0.5 wt%) were significantly superior to those on pure PCL scaffolds, and the cells exhibited typical fibroblast- and neuron-like morphologies with obvious pseudopods and mature appearance, respectively. A small amount of GO did not restrain the proliferation and viability of the mMSCs and PC12-L cells, which indicated appreciable cell affinity of GO. Moreover, the hybridization of GO nanosheets and PCL polymer dramatically enhanced the differentiation of the mMSCs and PC12-L cells into osteo- and neuro-like cells, respectively. All these results suggest that PCL/GO composite nanofibers could be a promising alternative material as biocompatible scaffolds for tissue engineering.

研究领域: 材料科学 · 生物材料 · 组织工程 · 纳米技术 · 细胞生物学
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