共查询到20条相似文献,搜索用时 15 毫秒
1.
Hahn SK Park JK Tomimatsu T Shimoboji T 《International journal of biological macromolecules》2007,40(4):374-380
Hyaluronic acid (HA) hydrogels prepared with three different crosslinking reagents were assessed by in vitro and in vivo degradation tests for various tissue engineering applications. Adipic acid dihydrazide grafted HA (HA-ADH) was synthesized and used for the preparation of methacrylated HA (HA-MA) with methacrylic anhydride and thiolated HA (HA-SH) with Traut's reagent (imminothiolane). (1)H NMR analysis showed that the degrees of HA-ADH, HA-MA, and HA-SH modification were 69, 29, and 56 mol%, respectively. HA-ADH hydrogel was prepared by the crosslinking with bis(sulfosuccinimidyl) suberate (BS(3)), HA-MA hydrogel with dithiothreitol (DTT) by Michael addition, and HA-SH hydrogel with sodium tetrathionate by disulfide bond formation. According to in vitro degradation tests, HA-SH hydrogel was degraded very fast, compared to HA-ADH and HA-MA hydrogels. HA-ADH hydrogel was degraded slightly faster than HA-MA hydrogel. Based on these results, HA-MA hydrogels and HA-SH hydrogels were implanted in the back of SD rats and their degradation was assessed according to the pre-determined time schedule. As expected from the in vitro degradation test results, HA-SH hydrogel was in vivo degraded completely only in 2 weeks, whereas HA-MA hydrogels were degraded only partially even in 29 days. The degradation rate of HA hydrogels were thought to be controlled by changing the crosslinking reagents and the functional group of HA derivatives. In addition, the state of HA hydrogel was another factor in controlling the degradation rate. Dried HA hydrogel at 37 degrees C for a day resulted in relatively slow degradation compared to the bulk HA hydrogel. There was no adverse effect during the in vivo tests. 相似文献
2.
Hydrogel dressings have significant advantages such as absorption of tissue exudate, maintenance of proper moist environment, and promotion of cell proliferation. However, facile preparation method and high-efficient antibacterial hydrogel dressings are still a great challenge. In this study, a facile approach to prepare antibacterial nanocomposite hydrogel dressing to accelerate healing was explored. The hydrogels consisted of quaternized chitosan and chemically cross-linked polyacrylamide, as well as silver nanoparticles (AgNPs) stabilized by chitosan. The synthesis of the hydrogels including the formation of AgNPs and polymerization of acrylamide was accomplished simultaneously under UV irradiation in 1 hour without adding initiator. The hydrogels showed favorable tensile strength of ∼100 kPa with elongation at break over 1000% and shear modulus of ∼104 Pa as well as suitable swelling ratio, which were appropriate for wound dressing. The combination of quaternized chitosan and AgNPs exhibited high-efficient and synergetic antibacterial performance with low cytotoxicity. In vivo animal experiments showed that the hydrogel can effectively prevent wound infection and promote wound healing. This study provides a facile method to produce antibacterial hydrogel wound dressing materials. 相似文献
3.
Hyaluronic acid (HA) is a naturally occurring polymer that holds considerable promise for tissue engineering applications. Current cross-linking chemistries often require a coupling agent, catalyst, or photoinitiator, which may be cytotoxic, or involve a multistep synthesis of functionalized-HA, increasing the complexity of the system. With the goal of designing a simpler one-step, aqueous-based cross-linking system, we synthesized HA hydrogels via Diels-Alder "click" chemistry. Furan-modified HA derivatives were synthesized and cross-linked via dimaleimide poly(ethylene glycol). By controlling the furan to maleimide molar ratio, both the mechanical and degradation properties of the resulting Diels-Alder cross-linked hydrogels can be tuned. Rheological and degradation studies demonstrate that the Diels-Alder click reaction is a suitable cross-linking method for HA. These HA cross-linked hydrogels were shown to be cytocompatible and may represent a promising material for soft tissue engineering. 相似文献
4.
To address the need for bioactive materials toward clinical applications in wound healing and tissue regeneration, an artificial protein was created by recombinant DNA methods and modified by grafting of poly(ethylene glycol) diacrylate. Subsequent photopolymerization of the acrylate-containing precursors yielded protein-graft-poly(ethylene glycol) hydrogels. The artificial protein contained repeating amino acid sequences based on fibrinogen and anti-thrombin III, comprising an RGD integrin-binding motif, two plasmin degradation sites, and a heparin-binding site. Two-dimensional adhesion studies showed that the artificial protein had specific integrin-binding capability based on the RGD motif contained in its fibrinogen-based sequence. Furthermore, heparin bound strongly to the protein's anti-thrombin III-based region. Protein-graft-poly(ethylene glycol) hydrogels were plasmin degradable, had Young's moduli up to 3.5 kPa, and supported three-dimensional outgrowth of human fibroblasts. Cell attachment in three dimensions resulted from specific cell-surface integrin binding to the material's RGD sequence. Hydrogel penetration by cells involved serine-protease mediated matrix degradation in temporal and spatial synchrony with cellular outgrowth. Protein-graft-poly(ethylene glycol) hydrogels represent a new and versatile class of biomimetic hybrid materials that hold clinical promise in serving as implants to promote wound healing and tissue regeneration. 相似文献
5.
In situ forming and rutin-releasing chitosan hydrogels as injectable dressings for dermal wound healing 总被引:1,自引:0,他引:1
An in situ gel-forming system composed of rutin- and tyramine-conjugated chitosan derivatives, horseradish peroxidase (HRP), and hydrogen peroxide (H(2)O(2)) was prepared and applied to dermal wound repair. Rutin was employed to enhance production and accumulation of extracellular matrix in the healing process. In vitro study demonstrates that released rutin significantly enhanced cell proliferation as compared with media without rutin. In vivo wound healing study was performed by injecting hydrogels on rat dorsal wounds with a diameter of 8 mm for 14 days. Histological results demonstrated that rutin-conjugated hydrogel exhibited enhancement of wound healing as compared with treatments with PBS, hydrogel without rutin, and a commercialized wound dressing (Duoderm). More specifically, rutin-conjugated hydrogels induced better defined formation of neo-epithelium and thicker granulation, which is closer to the original epithelial tissue. As a result, this study suggests that the in situ gel-forming system can be a promising injectable gel-type wound dressing. 相似文献
6.
We present a novel fully hydrophilic, hydrolytically degradable poly(ethylene glycol) (PEG) hydrogel suitable for soft tissue engineering and delivery of protein drugs. The gels were designed to overcome drawbacks associated with current PEG hydrogels (i.e., reaction mechanisms or degradation products that compromise protein stability): the highly selective and mild cross‐linking reaction allowed for encapsulating proteins prior to gelation without altering their secondary structure as shown by circular dichroism experiments. Further, hydrogel degradation and structure, represented by mesh size, were correlated to protein release. It was determined that polymer density had the most profound effect on protein diffusivity, followed by the polymer molecular weight, and finally by the specific chemical structure of the cross‐linker. By examining the diffusion of several model proteins, we confirmed that the protein diffusivity was dependent on protein size as smaller proteins (e.g., lysozyme) diffused faster than larger proteins (e.g., Ig). Furthermore, we demonstrated that the protein physical state was preserved upon encapsulation and subsequent release from the PEG hydrogels and contained negligible aggregation or protein–polymer adducts. These initial studies indicate that the developed PEG hydrogels are suitable for release of stable proteins in drug delivery and tissue engineering applications. Biotechnol. Bioeng. 2011; 108:197–206. © 2010 Wiley Periodicals, Inc. 相似文献
7.
Polysaccharides are being processed into biomaterials for numerous biological applications due to their native source in numerous tissues and biological functions. For instance, hyaluronic acid (HA) is found abundantly in the body, interacts with cells through surface receptors, and can regulate cellular behavior (e.g., proliferation, migration). HA was previously modified with reactive groups to form hydrogels that are degraded by hyaluronidases, either added exogenously or produced by cells. However, these hydrogels may be inhibitory and their applications are limited if the appropriate enzymes are not present. Here, for the first time, we synthesized HA macromers and hydrogels that are both hydrolytically (via ester group hydrolysis) and enzymatically degradable. The hydrogel degradation and growth factor release was tailored through the hydrogel cross-linking density (i.e., macromer concentration) and copolymerization with purely enzymatically degradable macromers. When mesenchymal stem cells (MSCs) were encapsulated in the hydrogels, cellular organization and tissue distribution was influenced by the copolymer concentration. Importantly, the distribution of released extracellular matrix molecules (e.g., chondroitin sulfate) was improved with increasing amounts of the hydrolytically degradable component. Overall, this new macromer allows for enhanced control over the structural evolution of the HA hydrogels toward applications as biomaterials. 相似文献
8.
《Critical reviews in biotechnology》2013,33(4):328-337
AbstractOptimal wound dressings should be capable of mechanical wound protection and also facilitate the healing process via maintenance of suitable environmental conditions and the controlled delivery of bioactive molecules. Hydrogels present suitable properties for wound-dressing applications such as good biocompatibility, together with a high water content, the latter of which is important for the maintenance of a moist environment and ready removal from the wound with a minimal level of associated pain. However, their properties as drug delivery systems can be improved by the use of cyclodextrins as cross-linking agents. Cyclodextrins have been extensively used as “carriers” on food, textile, cosmetic and, most especially, in the pharmaceutical industry in view of their powerful complexation abilities and biocompatibilities, together with further desirable characteristics. The conjugation of cyclodextrins with hydrogels may allow the achievement of an optimal wound-dressing material, because the hydrogel component will maintain the moist environment required for the healing process, and the cyclodextrin moiety has the ability to protect and modulate the release of bioactive molecules. Therefore, this review aims to gather information regarding cyclodextrin-based hydrogels for possible wound-dressing applications. 相似文献
9.
Rosalina Lara-Rico Claudia M. López-Badillo Jesús A. Claudio-Rizo Denis. A. Cabrera-Munguía Juan J. Becerra-Rodríguez Roberto Espinosa-Neira Brenda R. Cruz-Ortiz 《Biopolymers》2023,114(6):e23538
In this work, hydrogels based on semi-interpenetrating polymeric networks (semi-IPN) based on collagen-polyurethane-alginate were studied physicochemically and from different approaches for biomedical application. It was determined that the matrices in the hydrogel state are crosslinked by the formation of urea and amide bonds between the biopolymer chains and the polyurethane crosslinker. The increment in alginate content (0–40 wt%) significantly increases the swelling capacity, generating semi-crystalline granular structures with improved storage modulus and resistance to thermal, hydrolytic, and proteolytic degradation. The in vitro bioactivity results indicated that the composition of these novel hydrogels stimulates the metabolic activity of monocytes and fibroblasts, benefiting their proliferation; while in cancer cell lines, it was determined that the composition of these biomaterials decreases the metabolic activity of breast cancer cells after 48 h of stimulation, and for colon cancer cells their metabolic activity decreases after 72 h of contact for the hydrogel with 40 wt% alginate. The matrices show a behavior of multidose release of ketorolac, and a higher concentration of analgesic is released in the semi-IPN matrix. The inhibition capacity of Escherichia coli is higher if the polysaccharide concentration is low (10 wt%). The in vitro wound closure test (scratch test) results indicate that the hydrogel with 20 wt% alginate shows an improvement in wound closure at 15 days of contact. Finally, the bioactivity of mineralization was evaluated to demonstrate that these hydrogels can induce the formation of carbonated apatite on their surface. The engineered hydrogels show biomedical multifunctionality and they could be applied in soft and hard tissue healing strategies, anticancer therapies, and drug release devices. 相似文献
10.
为了获得更为理想的皮肤创口修复敷料,在海藻酸钠(SA)和聚丙烯酰胺(PAM)水凝胶的基础上复合人发角蛋白(KTN),制得KTN/SA/PAM水凝胶皮肤敷料.用电子万能测试机、扫描电子显微镜等对其进行表征,结果显示,KTN/SA/PAM水凝胶皮肤敷料拉伸强度为42.41 kPa,弹性模量11.19 kPa,接近人体皮肤组... 相似文献
11.
Hyaluronic acid (HA) is a linear polysaccharide naturally found in the eye and therefore is one of the most promising biomaterials for corneal endothelial regenerative medicine. This study reports, for the first time, the development of overrun-processed porous HA hydrogels for corneal endothelial cell (CEC) sheet transplantation and tissue engineering applications. The hydrogel carriers were characterized to examine their structures and functions. Evaluations of carbodiimide cross-linked air-dried and freeze-dried HA samples were conducted simultaneously for comparison. The results indicated that during the fabrication of freeze-dried HA discs, a technique of introducing gas bubbles in the aqueous biopolymer solutions can be used to enlarge pore structure and prevent dense surface skin formation. Among all the groups studied, the overrun-processed porous HA carriers show the greatest biological stability, the highest freezable water content and glucose permeability, and the minimized adverse effects on ionic pump function of rabbit CECs. After transfer and attachment of bioengineered CEC sheets to the overrun-processed HA hydrogel carriers, the therapeutic efficacy of cell/biopolymer constructs was tested using a rabbit model with corneal endothelial dysfunction. Clinical observations including slit-lamp biomicroscopy, specular microscopy, and corneal thickness measurements showed that the construct implants can regenerate corneal endothelium and restore corneal transparency at 4 weeks postoperatively. Our findings suggest that cell sheet transplantation using overrun-processed porous HA hydrogels offers a new way to reconstruct the posterior corneal surface and improve endothelial tissue function. 相似文献
12.
Porous hydrogels of poly(ethylene glycol) (PEG) have been shown to facilitate vascularized tissue formation. However, PEG hydrogels exhibit limited degradation under physiological conditions which hinders their ultimate applicability for tissue engineering therapies. Introduction of poly(L-lactic acid) (PLLA) chains into the PEG backbone results in copolymers that exhibit degradation via hydrolysis that can be controlled, in part, by the copolymer conditions. In this study, porous, PEG-PLLA hydrogels were generated by solvent casting/particulate leaching and photopolymerization. The influence of polymer conditions on hydrogel architecture, degradation and mechanical properties was investigated. Autofluorescence exhibited by the hydrogels allowed for three-dimensional, non-destructive monitoring of hydrogel structure under fully swelled conditions. The initial pore size depended on particulate size but not polymer concentration, while degradation time was dependent on polymer concentration. Compressive modulus was a function of polymer concentration and decreased as the hydrogels degraded. Interestingly, pore size did not vary during degradation contrary to what has been observed in other polymer systems. These results provide a technique for generating porous, degradable PEG-PLLA hydrogels and insight into how the degradation, structure, and mechanical properties depend on synthesis conditions. 相似文献
13.
Sannino A Madaghiele M Conversano F Mele G Maffezzoli A Netti PA Ambrosio L Nicolais L 《Biomacromolecules》2004,5(1):92-96
The aim of this work is to obtain a chemically cross-linked hydrogel from hyaluronic acid and cellulose derivatives that exhibits sensitivity to variation of the composition of the external absorbing medium and an equilibrium sorption capacity higher than a common hyaluronic acid-based hydrogel, in view of its potential use in prevention of postsurgical soft tissue adhesion. This has been achieved by chemical stabilization of hyaluronic acid (HA) and cellulose derivatives, hydroxyethylcellulose (HEC) and carboxymethylcellulose (CMCNa) through the difunctional cross-linker divinyl sulfone. Significant increase in sorption capacity, both in water and in water solutions at different ionic strength, has been observed for these samples in comparison with hydrogels obtained through chemical stabilization of hyaluronic acid. Moreover, different dehydration procedures adopted for the xerogel synthesis have been used, which resulted in a modulation of the equilibrium sorption capacity. Hyaluronic acid stability has been confirmed by means of NMR analysis. 相似文献
14.
Injectable hyaluronic acid (HA) hydrogels cross-linked via disulfide bond are synthesized using a thiol-disulfide exchange reaction. The production of small-molecule reaction product, pyridine-2-thione, allows the hydrogel formation process to be monitored quantitatively in real-time by UV spectroscopy. Rheological tests show that the hydrogels formed within minutes at 37 °C. Mechanical properties and equilibrium swelling degree of the hydrogels can be controlled by varying the ratio of HA pyridyl disulfide and macro-cross-linker PEG-dithiol. Degradation of the hydrogels was achieved both enzymatically and chemically by disulfide reduction with distinctly different kinetics and profiles. In the presence of hyaluronidase, hydrogel mass loss over time was linear and the degradation was faster at higher enzyme concentrations, suggesting surface-limited degradation. The kinetics of hydrogel erosion by glutathione was not linear, nor did the erosion rate correlate linearly with glutathione concentration, suggesting a bulk erosion mechanism. A cysteine-containing chemokine, stromal cell-derived factor 1α, was successfully encapsulated in the hydrogel and released in vitro without chemical alteration. Several different cell types, including fibroblasts, endothelial cells, and mesenchymal stem cells, were successfully encapsulated in the hydrogels with high cell viability during and after the encapsulation process. Substantial cell viability in the hydrogels was maintained up to 7 days in culture despite the lack of adhesion between the HA matrix and the cells. The facile synthesis of disulfide-cross-linked, dual-responsive degradable HA hydrogels may enable further development of bioactive matrices potentially suitable for tissue engineering and drug delivery applications. 相似文献
15.
Shiqing Ma Han Hu Jinzhe Wu Xuewen Li Xinying Ma Zhezhe Zhao Zihao Liu Chenxuan Wu Bo Zhao Yonglan Wang Wei Jing 《Cell proliferation》2022,55(4)
ObjectivesDiabetic wound healing remains a global challenge in the clinic and in research. However, the current medical dressings are difficult to meet the demands. The primary goal of this study was to fabricate a functional hydrogel wound dressing that can provide an appropriate microenvironment and supplementation with growth factors to promote skin regeneration and functional restoration in diabetic wounds.Materials and MethodsSmall extracellular vesicles (sEVs) were bound to the porcine small intestinal submucosa‐based hydrogel material through peptides (SC‐Ps‐sEVs) to increase the content and achieve a sustained release. NIH3T3 cell was used to evaluate the biocompatibility and the promoting proliferation, migration and adhesion abilities of the SC‐Ps‐sEVs. EA.hy926 cell was used to evaluate the stimulating angiogenesis of SC‐Ps‐sEVs. The diabetic wound model was used to investigate the function/role of SC‐Ps‐sEVs hydrogel in promoting wound healing.ResultsA functional hydrogel wound dressing with good mechanical properties, excellent biocompatibility and superior stimulating angiogenesis capacity was designed and facilely fabricated, which could effectively enable full‐thickness skin wounds healing in diabetic rat model.ConclusionsThis work led to the development of SIS, which shows an unprecedented combination of mechanical, biological and wound healing properties. This functional hydrogel wound dressing may find broad utility in the field of regenerative medicine and may be similarly useful in the treatment of wounds in epithelial tissues, such as the intestine, lung and liver.Schematic illustration showing synthesis of the SC‐Ps scaffold dressing and nanoscale sEVs loaded SC‐Ps scaffold dressing and the potential application of the dressings in diabetic wound healing and skin reconstruction. 相似文献
16.
The role of oxidised regenerated cellulose/collagen in chronic wound repair and its potential mechanism of action 总被引:3,自引:0,他引:3
Cullen B Watt PW Lundqvist C Silcock D Schmidt RJ Bogan D Light ND 《The international journal of biochemistry & cell biology》2002,34(12):1544-1556
Normal wound healing is a carefully controlled balance of destructive processes necessary to remove damaged tissue and repair processes which lead to new tissue formation. Proteases and growth factors play a pivotal role in regulating this balance, and if disrupted in favour of degradation then delayed healing ensues; a trait of chronic wounds. Whilst there are many types of chronic wounds, biochemically they are thought to be similar in that they are characterised by a prolonged inflammatory phase, which results in elevated levels of proteases and diminished growth factor activity. This increase in proteolytic activity and subsequent degradation of growth factors is thought to contribute to the net tissue loss associated with these chronic wounds.
In this study, we describe a new wound treatment, comprising oxidised regenerated cellulose and collagen (ORC/collagen), which can redress this imbalance and modify the chronic wound environment. We demonstrate that ORC/collagen can inactivate potentially harmful factors such as proteases, oxygen free radicals and excess metal ions present in chronic wound fluid, whilst simultaneously protecting positive factors such as growth factors and delivering them back to the wound.
These characteristics suggest a beneficial role for this material in helping to re-balance the chronic wound environment and therefore promote healing. 相似文献
17.
Matú oma Veronika Lachov Petra Mitrengov Peter Gl 《Current issues in molecular biology》2021,43(1):127
Estrogen deprivation is one of the major factors responsible for many age-related processes including poor wound healing in postmenopausal women. However, the reported side-effects of estrogen replacement therapy (ERT) have precluded broad clinical administration. Therefore, selective estrogen receptor modulators (SERMs) have been developed to overcome the detrimental side effects of ERT on breast and/or uterine tissues. The use of natural products isolated from plants (e.g., soy) may represent a promising source of biologically active compounds (e.g., genistein) as efficient alternatives to conventional treatment. Genistein as natural SERM has the unique ability to selectively act as agonist or antagonist in a tissue-specific manner, i.e., it improves skin repair and simultaneously exerts anti-cancer and chemopreventive properties. Hence, we present here a wound healing phases-based review of the most studied naturally occurring SERM. 相似文献
18.
Toward the development of synthetic bioactive materials to support tissue repair, we present here the design, production, and characterization of genetically engineered protein polymers carrying specific key features of the natural extracellular matrix, as well as cross-linking with functionalized poly(ethylene glycol) (PEG) to form hybrid hydrogel networks. The repeating units of target recombinant protein polymers contain a cell-binding site for ligation of cell-surface integrin receptors and substrates for plasmin and matrix metalloproteinases (MMPs), proteases implicated in wound healing and tissue regeneration. Hydrogels were formed under physiological conditions via Michael-type conjugate addition of vinyl sulfone groups of end-functionalized PEG with thiols of cysteine residues, representing designed chemical cross-linking sites within recombinant proteins. Cross-linking kinetics was shown to increase with the pH of precursor solutions. The elastic moduli (G') and swelling ratios (Q(m)) of the resulting hydrogels could be varied as a function of the stoichiometry of the reacting groups and precursor concentration. Optima of G' and Q(m), maximum and minimum, respectively, were obtained at stoichiometry ratios r slightly in excess of 1 (r = cysteine/vinyl sulfone). The pool of technologies utilized here represents a promising approach for the development of artificial matrixes tailored for specific medical applications. 相似文献
19.
Enzymatic degradation of hyaluronan hydrogels with different capacity for in situ bio‐mineralization
下载免费PDF全文
![点击此处可从《Biopolymers》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Dmitri Ossipov 《Biopolymers》2018,109(2)
In situ cross‐linked hyaluronan (HA) hydrogels with different capacities for biomineralization were prepared and their enzymatic degradation was monitored. Covalent incorporation of bisphosphonates (BPs) into HA hydrogel results in the increased stiffness of the hydrogel in comparison with the unmodified HA hydrogel of the same cross‐linking density. The rate of enzymatic degradation of HABP hydrogel was significantly lower than the rate of degradation of control HA hydrogel in vitro. This effect is observed only in the presence of calcium ions that strongly bind to the matrix‐anchored BP groups and promote further mineralization of the matrix. The degradation of the hydrogels was followed by noninvasive fluorescence measurements enabled after mild and chemoselective labeling of cross‐linkable HA derivatives with a fluorescent tag. 相似文献
20.
A one-step synthesis of a curcumin-derived hydrogel (curcumin content of 25-75 mol %) is reported. Curcumin is incorporated into the hydrogel backbone and cross-linked through biodegradable carbonate linkages. Curcumin as a part of the polymer backbone is protected from oxidation and degradation, while hydrogel hydrolysis results in the release of active curcumin. Nontoxic poly(ethylene glycol) and desaminotyrosyl-tyrosine ethyl ester are used to tune the hydrophilic/hydrophobic hydrogel properties. In this way, hydrogels with a wide range of physical properties including water-uptake (100-550%) and compression moduli (7-100 kPa) were obtained. Curcumin release is swelling-controlled and could be extended to 80 days. In vitro, curcumin-derived hydrogels showed selective cytotoxicity against MDA-MB-231 (IC(50) 9 μM) breast cancer cells but no cytotoxicity to noncancerous quiescent human dermal fibroblasts even at high curcumin concentrations (160 μM). One possible application of these curcumin-derived hydrogels is as soft tissue filler after surgical removal of cancerous tissue. 相似文献