hydrogel matrix
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Gels ◽  
2022 ◽  
Vol 8 (1) ◽  
pp. 56
Author(s):  
Hongdou Shen ◽  
Pei Wang ◽  
Xiaoke Han ◽  
Mengli Ma ◽  
Yinghui Shang ◽  
...  

Promising wound dressings can achieve rapid soft-tissue filling while refactoring the biochemical and biophysical microenvironment to recruit endogenous cells, facilitating tissue healing, integration, and regeneration. In this study, a tissue biomolecule-responsive hydrogel matrix, employing natural silk fibroin (SF) as a functional biopolymer and haemoglobin (Hb) as a peroxidase-like biocatalyst, was fabricated through cascade enzymatic crosslinking. The hydrogels possessed mechanical tunability and displayed adjustable gelation times. A tyrosine unit on SF stabilised the structure of Hb during the cascade oxidation process; thus, the immobilized Hb in SF hydrogels exhibited higher biocatalytic efficiency than the free enzyme system, which provided a continuously antioxidative system. The regulation of the dual enzyme ratio endowed the hydrogels with favourable biocompatibility, biodegradability, and adhesion strength. These multifunctional hydrogels provided a three-dimensional porous extracellular matrix-like microenvironment for promoting cell adhesion and proliferation. A rat model with a full-thickness skin defect revealed accelerated wound regeneration via collagen deposition, re-epithelialisation and revascularisation. Enzyme-loaded hydrogels are an attractive and high-safety biofilling material with the potential for wound healing, tissue regeneration, and haemostasis.


Author(s):  
Brian A. Aguado ◽  
Cierra J. Walker ◽  
Joseph C. Grim ◽  
Megan E. Schroeder ◽  
Dilara Batan ◽  
...  

Background: Aortic valve stenosis (AVS) is a sexually dimorphic disease, with women often presenting with sustained fibrosis and men with more extensive calcification. However, the intracellular molecular mechanisms that drive these clinically important sex differences remain under explored. Methods: Hydrogel scaffolds were designed to recapitulate key aspects of the valve tissue microenvironment and serve as a culture platform for sex-specific valvular interstitial cells (VICs; precursors to pro-fibrotic myofibroblasts). The hydrogel culture system was used to interrogate intracellular pathways involved in sex-dependent VIC-to-myofibroblast activation and deactivation. RNA-sequencing was used to define pathways involved in driving sex-dependent activation. Interventions using small molecule inhibitors and small interfering RNA (siRNA) transfections were performed to provide mechanistic insight into sex-specific cellular responses to microenvironmental cues, including matrix stiffness and exogenously delivered biochemical factors. Results: In both healthy porcine and human aortic valves, female leaflets had higher baseline activation of the myofibroblast marker, alpha-smooth muscle actin (α-SMA), compared to male leaflets. When isolated and cultured, female porcine and human VICs had higher levels of basal α-SMA stress fibers that further increased in response to the hydrogel matrix stiffness, both of which were higher than male VICs. A transcriptomic analysis of male and female porcine VICs revealed Rho-associated protein kinase (RhoA/ROCK) signaling as a potential driver of this sex-dependent myofibroblast activation. Further, we found that genes that escape X-chromosome inactivation, such as BMX and STS (encoding for Bmx non-receptor tyrosine kinase and steroid sulfatase, respectively) partially regulate the elevated female myofibroblast activation via RhoA/ROCK signaling. This finding was confirmed by treating male and female VICs with endothelin-1 and plasminogen activator inhibitor-1, factors that are secreted by endothelial cells and known to drive myofibroblast activation via RhoA/ROCK signaling. Conclusions: Together, in vivo and in vitro results confirm sex-dependencies in myofibroblast activation pathways and implicate genes that escape X-chromosome inactivation in regulating sex differences in myofibroblast activation and subsequent AVS progression. Our results underscore the importance of considering sex as a biological variable to understand the molecular mechanisms of AVS and help guide sex-based precision therapies.


2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Brigitta Dúzs ◽  
Gábor Holló ◽  
Gábor Schuszter ◽  
Dezső Horváth ◽  
Ágota Tóth ◽  
...  

AbstractThe design and synthesis of crystalline materials are challenging due to the proper control over the size and polydispersity of the samples, which determine their physical and chemical properties and thus applicability. Metal − organic frameworks (MOFs) are promising materials in many applications due to their unique structure. MOFs have been predominantly synthesized by bulk methods, where the concentration of the reagents gradually decreased, which affected the further nucleation and crystal growth. Here we show an out-of-equilibrium method for the generation of zeolitic imidazolate framework-8 (ZIF-8) crystals, where the non-equilibrium crystal growth is maintained by a continuous two-side feed of the reagents in a hydrogel matrix. The size and the polydispersity of the crystals are controlled by the fixed and antagonistic constant mass fluxes of the reagents and by the reaction time. We also present that our approach can be extended to synthesize gold nanoparticles in a redox process.


2022 ◽  
Author(s):  
Shardul Bhusari ◽  
Shrikrishnan Sankaran ◽  
Aranzazu del Campo

Engineered living materials (ELMs) are a new class of materials in which living organisms incorporated into diffusive matrices uptake a fundamental role in material composition and function. Understanding how the spatial confinement in 3D affects the behavior of the embedded cells is crucial to design and predict ELM functions, regulate and minimize their environmental impact and facilitate their translation into applied materials. This study investigates the growth and metabolic activity of bacteria within an associative hydrogel network (Pluronic-based) with mechanical properties that can be tuned by introducing a variable degree of acrylate crosslinks. Individual bacteria distributed in the hydrogel matrix at low density form functional colonies whose size is controlled by the extent of permanent crosslinks. With increasing stiffness and decreasing plasticity of the matrix, a decrease in colony volumes and an increase in their sphericity is observed. Protein production surprisingly follows a different pattern with higher production yields occurring in networks with intermediate permanent crosslinking degrees. These results demonstrate that, bacterial mechanosensitivity can be used to control and regulate the composition and function of ELMs by thoughtful design of the encapsulating matrix, and by following design criteria with interesting similarities to those developed for 3D culture of mammalian cells.


2022 ◽  
Author(s):  
Zhongliang Jiang ◽  
Fang-Yi Lin ◽  
Kun Jiang ◽  
Han Nguyen ◽  
Chun-Yi Chang ◽  
...  

Mesenchymal stem cells (MSCs)-based therapies have been widely used to promote tissue regeneration and to modulate immune/inflammatory response. The therapeutic potential of MSCs can be further improved by forming multi-cellular spheroids. Meanwhile, hydrogels with macroporous structures are advantageous for improving mass transport properties for the cell-laden matrices. Herein, we report the fabrication of MSC-laden macroporous hydrogel scaffolds through incorporating rapidly dissolvable spherical cell-laden microgels. Dissolvable microgels were fabricated by tandem droplet-microfluidics and thiol-norbornene photopolymerization using a novel fast-degrading macromer poly(ethylene glycol)-norbornene-dopamine (PEGNB-Dopa). The cell-laden microgels were subsequently encapsulated within another bulk hydrogel matrix, whose porous structure was generated efficiently by the rapid degradation of the PEGNB-Dopa microgels. The cytocompatibility of this in situ pore-forming approach was demonstrated with multiple cell types. Furthermore, adjusting the stiffness and cell adhesiveness of the bulk hydrogels afforded the formation of solid cell spheroids or hollow spheres. The assembly of solid or hollow MSC spheroids led to differential activation of AKT pathway. Finally, MSCs solid spheroids formed in situ within the macroporous hydrogels exhibited robust secretion of HGF, VEGF-A, IL-6, IL-8, and TIMP-2. In summary, this platform provides an innovative method for forming cell-laden macroporous hydrogels for a variety of future biomedical applications.


2021 ◽  
Vol 20 (2) ◽  
pp. 235-246
Author(s):  
Snigdha Bhardwaj ◽  
Ashutosh Tiwari

Nanomedicine, a novel concept, bears much hope in delivering drug candidates having low solubility and bioavailability. Nano-emulgel, one of the emerging tools, is considered as ideal carriers for the topical delivery of lipophilic drugs to overcome these challenges in the management of psoriasis and related skin problems. Psoriasis is an auto-immune and chronic inflammatory disease affecting 2-3% population of the world. Current available treatment of psoriasis has limitations such as systemic side effects and low percutaneous permeation, which evokes a dire need to develop an alternative lipoidal nanocarrier system. Nano-emulgel is basically formed by admixing nanoemulsion system with a hydrogel matrix using both high and low energy methods. Various literatures have been reported for lipoidal nanocarriers in topical treatment suggesting reduced dose, improved percutaneous absorption and better bioavailability of lipophilic drugs with nano-emulgel delivery via topical route. Several approved marketed preparations are available that strongly support the stability of these nanocarriers in respect to its efficacy and safety. This supports the fact of using topical nano-emulgel system to deliver lipophilic drugs to overcome the sufferings from oral delivery and improved patient compliance. Therefore, it is suggested as a potential system that can be used for an effective management of psoriasis via topical route in near future. Dhaka Univ. J. Pharm. Sci. 20(2): 235-246, 2021 (December)


2021 ◽  
Vol 23 (1) ◽  
pp. 321
Author(s):  
Katarzyna Reczyńska-Kolman ◽  
Kinga Hartman ◽  
Konrad Kwiecień ◽  
Monika Brzychczy-Włoch ◽  
Elżbieta Pamuła

Due to growing antimicrobial resistance to antibiotics, novel methods of treatment of infected wounds are being searched for. The aim of this research was to develop a composite wound dressing based on natural polysaccharides, i.e., gellan gum (GG) and a mixture of GG and alginate (GG/Alg), containing lipid nanoparticles loaded with antibacterial peptide—nisin (NSN). NSN-loaded stearic acid-based nanoparticles (NP_NSN) were spherical with an average particle size of around 300 nm and were cytocompatible with L929 fibroblasts for up to 500 µg/mL. GG and GG/Alg sponges containing either free NSN (GG + NSN and GG/Alg + NSN) or NP_NSN (GG + NP_NSN and GG/Alg + NP_NSN) were highly porous with a high swelling capacity (swelling ratio above 2000%). Encapsulation of NSN within lipid nanoparticles significantly slowed down NSN release from GG-based samples for up to 24 h (as compared to GG + NSN). The most effective antimicrobial activity against Gram-positive Streptococcus pyogenes was observed for GG + NP_NSN, while in GG/Alg it was decreased by interactions between NSN and Alg, leading to NSN retention within the hydrogel matrix. All materials, except GG/Alg + NP_NSN, were cytocompatible with L929 fibroblasts and did not cause an observable delay in wound healing. We believe that the developed materials are promising for wound healing application and the treatment of bacterial infections in wounds.


Micromachines ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 32
Author(s):  
Yufeng Tao ◽  
Chengchangfeng Lu ◽  
Chunsan Deng ◽  
Jing Long ◽  
Yunpeng Ren ◽  
...  

Rapid fabricating and harnessing stimuli-responsive behaviors of microscale bio-compatible hydrogels are of great interest to the emerging micro-mechanics, drug delivery, artificial scaffolds, nano-robotics, and lab chips. Herein, we demonstrate a novel femtosecond laser additive manufacturing process with smart materials for soft interactive hydrogel micro-machines. Bio-compatible hyaluronic acid methacryloyl was polymerized with hydrophilic diacrylate into an absorbent hydrogel matrix under a tight topological control through a 532 nm green femtosecond laser beam. The proposed hetero-scanning strategy modifies the hierarchical polymeric degrees inside the hydrogel matrix, leading to a controllable surface tension mismatch. Strikingly, these programmable stimuli-responsive matrices mechanized hydrogels into robotic applications at the micro/nanoscale (<300 × 300 × 100 μm3). Reverse high-freedom shape mutations of diversified microstructures were created from simple initial shapes and identified without evident fatigue. We further confirmed the biocompatibility, cell adhesion, and tunable mechanics of the as-prepared hydrogels. Benefiting from the high-efficiency two-photon polymerization (TPP), nanometer feature size (<200 nm), and flexible digitalized modeling technique, many more micro/nanoscale hydrogel robots or machines have become obtainable in respect of future interdisciplinary applications.


Materials ◽  
2021 ◽  
Vol 14 (24) ◽  
pp. 7652
Author(s):  
Sylwia Fiejdasz ◽  
Adriana Gilarska ◽  
Tomasz Strączek ◽  
Maria Nowakowska ◽  
Czesław Kapusta

The paper presents results of our studies on hybrid materials based on polymers of natural origin containing superparamagnetic iron oxide nanoparticles (SPIONs). Such nanoparticles, coated with the chitosan derivative, were immobilized in a chitosan-collagen hydrogel matrix by crosslinking with genipin. Three types of biopolymer matrices of different collagen-to-chitosan ratios were studied. A thorough magnetic characterization was performed, including magnetic susceptibility, magnetization, and hysteresis loop measurements in a temperature range of 4 K to 300 K and a magnetic field induction up to 8 Tesla. The effect of SPION immobilization and material composition on the magnetic properties of the hybrids was investigated. The results showed that hybrid materials with covalently bounded SPIONs preserved the superparamagnetic character of SPIONs and exhibited promising magnetic properties, which are important for their potential applications.


Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7484
Author(s):  
Ilja Gasan Osojnik Črnivec ◽  
Tigran Neresyan ◽  
Yuliana Gatina ◽  
Vid Kolmanič Bučar ◽  
Mihaela Skrt ◽  
...  

Adverse environmental conditions are severely limiting the use of microorganisms in food systems, such as probiotic delivery, where low pH causes a rapid decrease in the survival of ingested bacteria, and mixed-culture fermentation, where stepwise changes and/or metabolites of individual microbial groups can hinder overall growth and production. In our study, model probiotic lactic acid bacteria (L. plantarum ATCC 8014, L. rhamnosus GG) and yeasts native to dairy mixed cultures (Kluyveromyces marxianus ZIM 1868) were entrapped in an optimized (cell, alginate and hardening solution concentration, electrostatic working parameters) Ca-alginate system. Encapsulated cultures were examined for short-term survival in the absence of nutrients (lactic acid bacteria) and long-term performance in acidified conditions (yeasts). In particular, the use of encapsulated yeasts in these conditions has not been previously examined. Electrostatic manufacturing allowed for the preparation of well-defined alginate microbeads (180–260 µm diameter), high cell-entrapment (95%) and viability (90%), and uniform distribution of the encapsulated cells throughout the hydrogel matrix. The entrapped L. plantarum maintained improved viabilities during 180 min at pH 2.0 (19% higher when compared to the free culture), whereas, L. rhamnosus appeared to be less robust. The encapsulated K. marxianus exhibited double product yields in lactose- and lactic acid-modified MRS growth media (compared to an unfavorable growth environment for freely suspended cells). Even within a conventional encapsulation system, the pH responsive features of alginate provided superior protection and production of encapsulated yeasts, allowing several applications in lacto-fermented or acidified growth environments, further options for process optimization, and novel carrier design strategies based on inhibitor charge expulsion.


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