60:. Chemical cross-linking involved formation of covalent bonds between polymer chains. Chemically cross-linked hydrogel dressings are synthesized by chain-growth polymerization, step-growth polymerization, enzymes, or irradiation polymerization. Synthetic dressings incorporating nanoparticles such as PVA and polyethylene glycol (PEG) are assembled using chemical cross-linking mechanisms. Physically cross-linked hydrogel dressings are assembled via ionic interaction, hydrogen bonding, hydrophobic interactions, or crystallization. Physically cross-linked hydrogels disintegrate due to local changes in pH, ionic strength, and temperature. Natural dressings incorporating polysaccharides and proteoglycans/proteins form a 3D network using physical cross-linking. Hydrogel dressings mimic the cross-linked 3D network of extracellular matrix fibers in human skin.
113:"Smart" hydrogels which are stimuli-responsive (i.e. thermoresponsive, bioresponsive, pH-responsive, photoresponsive, and redox-responsive) are also being produced. pH-responsive hydrogel dressings which release growth factors and antibiotic agents as the pH of the wound increases from normal skin levels (pH 4–6) to internal levels (pH ~7.4). Redox-responsive hydrogel dressings can be disintegrated on-demand by addition of a reducing agent. Assembly of the 3D network of photoresponsive hydrogel dressings is initiated by UV radiation. Thermoresponsive hydrogel dressings which exhibit temperature-dependent sol-gel transition and/or temperature-dependent drug release.
80:(AMPs) and chitosan have inherent antimicrobial activity. The antimicrobial properties of hydrogel dressings can be enhanced by addition of metal nanoparticles, antibiotics, or other antimicrobial agents. Silver and gold nanoparticles can also be incorporated into hydrogel dressings to enhance antimicrobial activity. Some hydrogel dressings have antibiotics such as ciprofloxacin and amoxicillin incorporated into their structure which are unloaded into the wound as fluid is exchanged. Some hydrogel dressings have incorporated stimuli-responsive nitric oxide-releasing agents and other antimicrobial agents.
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uncross-linked state. Hydrogel dressings can absorb up to 600 times their initial amount of water, including fluid-based wound exudates. Hydrogels are effective biomaterials for wound dressings and tissue engineering because they exchange fluid, hydrating necrotic tissues. The absorption of secretions causes the hydrogel dressing to swell, expanding the cross links in the polymer chains. The expanded 3D cross-linked network can irreversibly incorporate pathogens and detritus, thereby removing them from the wound.
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dressings because they can conform to the shape of the wound bed and they facilitate autolytic debridement. Impregnated hydrogel dressings are dry dressings (e.g. gauzes) saturated with an amorphous hydrogel. Sprayable hydrogel dressings are composed of amorphous hydrogels which rapidly increase in viscosity after application. Sprayable hydrogels have also been shown to increase the penetration and efficacy of therapeutic agents.
27:
infection, retain moisture, promote optimum adhesion to tissues, and satisfy the basic requirements of biocompatibility. Hydrogel dressings can also be designed to respond to changes in the microenvironment at the wound bed. Hydrogel dressings should promote an appropriate microenvironment for angiogenesis, recruitment of fibroblasts, and cellular proliferation.
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accelerate healing in partial and full thickness burn wounds of varying size. Other studies have shown that hydrogel dressings accelerate healing in radioactive skin injuries and dog bite wounds. Hydrogel dressings decrease the healing time of traumatic skin injuries by an average 5.28 days and reduce the pain reported by patients.
63:
Hydrogels can be formed through a self-assembly process in which monomers diffuse in solution then form non covalent interactions. Hydrogels used in wound dressings can be self-assembled upon addition of divalent metal cations or electrically charged polysaccharides due to electrostatic interactions.
42:
such as polyvinyl alcohol (PVA). Self-assembling designer peptide hydrogels are another type of synthetic hydrogel in development. Natural hydrogel dressings are further subdivided into either polysaccharide-based (e.g. alginates) or proteoglycan- and/or protein-based (e.g. collagen). Hybrid hydrogel
100:
Self-healing hydrogels automatically and reversibly repair damage done due to mechanical and chemical stress. Self-healing mechanisms can involve "dynamic covalent bonding, non-covalent interactions" and mixed interactions. Covalent interactions involved in self-healing include Schiff base formation
104:
Hydrogel dressings are available in sheet, amorphous, impregnated, or sprayable forms. Sheet-form hydrogel dressings are non-adhesive against the wound and are effective in healing partial-thickness wounds. Amorphous hydrogels are more effective in treatment of full-thickness wounds than sheet-form
199:
Hydrogels may be modified to incorporate metal cations (e.g. copper (II)), degradable linkers (e.g. dextran), and adhesive functional groups (e.g. RGD). Integrating biological derivatives into synthetic hydrogels allows producers to tailor binding affinities and specificity, mechanical properties,
121:
The efficacy of hydrogel dressings has been assessed on various wound types. There is some evidence to suggest that hydrogels are effective dressings for chronic wounds including pressure ulcers, diabetic ulcers, and venous ulcers although the results are uncertain. Hydrogels have been shown to
96:
Wound dressings should be stretchable to prevent tearing. Hai Lei et al. demonstrated that poor elasticity and hysteresis in naturally-derived protein-based hydrogels can be remedied by the addition of polyprotein cross-linkers. The flexibility of hydrogels can also be enhanced by incorporating
72:
Cross-linking of soluble hydrophilic monomers forms a 3D insoluble netted structure which can incorporate a large amount of water. The 3D polymeric network of hydrogels is highly hydrated with 90-99% water w/w; it is capable of binding many times more water molecules when assembled than in the
26:
are three-dimensional networks consisting of chemically or physically cross-linked hydrophilic polymers. The insoluble hydrophilic structures absorb polar wound exudates and allow oxygen diffusion at the wound bed to accelerate healing. Hydrogel dressings can be designed to prevent bacterial
30:
Hydrogels respond elastically to applied stress; gels made from materials like collagen exhibit high toughness and low sliding friction, reducing damage from mechanical stress. Hydrogel dressings should possess mechanical and physical properties similar to the 3D microenvironment of the
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De Giglio, E.; Cometa, S.; Ricci, M.A.; Cafagna, D.; Savino, A.M.; Sabbatini, L.; Orciani, M.; Ceci, E.; Novello, L.; Tantillo, G.M.; Mattioli-Belmonte, M. (February 2011). "Ciprofloxacin-modified electrosynthesized hydrogel coatings to prevent titanium-implant-associated infections".
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and disulfide exchange. Non-covalent interactions are generally less stable and make the hydrogel more sensitive to microenvironmental changes (e.g. pH, temperature). Some hydrogel dressings are self-healing due to mixed mechanisms such as host-guest and protein-ligand interactions.
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Mattioli-Belmonte, M.; Zizzi, A.; Lucarini, G.; Giantomassi, F.; Biagini, G.; Tucci, G.; Orlando, F.; Provinciali, M.; Carezzi, F.; Morganti, P. (September 2007). "Chitin
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via hydrophobic interactions can be induced in amphiphilic polysaccharides-based gels by addition of water; it can also be induced in non amphiphilic polysaccharide-based hydrogels by addition of hydrophobic grafts.
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reactions of quinones. The adhesive properties of hydrogels have been shown to be enhanced by addition of positively charged microgels (MR) into the 3D matrix to increase electrostatic and hydrophobic interactions.
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Cereceres, Stacy; Lan, Ziyang; Bryan, Laura; Whitely, Michael; Wilems, Thomas; Greer, Hunter; Alexander, Ellen Ruth; Taylor, Robert J.; Bernstein, Lawrence; Cohen, Noah; Whitfield-Cargile, Canaan (June 2019).
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Hydrogel dressings can be sorted into the categories: synthetic, natural, and hybrid. Synthetic hydrogel dressings have been produced using biomimetic extracellular matrix
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microgels into the matrix. Hydrogel dressings mimic the fibrous nature of native ECM to maintain cell-to-cell communication at the wound bed for tissue regeneration.
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Zhang, Lijun; Yin, Hanxiao; Lei, Xun; Lau, Johnson N. Y.; Yuan, Mingzhou; Wang, Xiaoyan; Zhang, Fangyingnan; Zhou, Fei; Qi, Shaohai; Shu, Bin; Wu, Jun (2019-11-21).
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of human skin. Hydrogel wound dressings are designed to have a mechanism for application and removal which minimizes further trauma to tissues.
2161:
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187:(PU), and poly(lactide-co-glycolide) (PLGA). Synthetic hydrogel dressings may also be formed from designer peptides. Researchers are applying
2741:"Transparent crosslinked ultrashort peptide hydrogel dressing with high shape-fidelity accelerates healing of full-thickness excision wounds"
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1152:"Characterization of pHEMA-based hydrogels that exhibit light-induced bactericidal effect via release of NO"
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2627:"A review on polymeric hydrogel membranes for wound dressing applications: PVA-based hydrogel dressings"
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17:
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Hydrogel dressings can adhere directly to the wound bed under normal physiological conditions via
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Some hydrogel dressings have intrinsic antimicrobial properties. Hydrogel dressings formed from
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950:"Tryptophan- and arginine-rich antimicrobial peptides: Structures and mechanisms of action"
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Polysaccharide-based hydrogel dressings have been synthesized from polymers such as
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Synthetic hydrogel dressings may be derived from synthetic polymers such as
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1989:Cochrane Database of Systematic Reviews
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2588:10.1016/j.msec.2019.03.093
2536:10.1016/j.msec.2020.110837
1336:10.1038/s41467-020-17877-z
668:10.1016/j.nimb.2006.11.101
109:"Smart" hydrogel dressings
15:
2700:10.1007/s40204-018-0083-4
2472:Macromolecular Bioscience
2059:10.3389/fbioe.2021.740863
1702:10.1186/s41038-018-0138-8
1168:10.1007/s10856-009-3795-0
373:"Bioresponsive hydrogels"
163:, kappa-carrageenan, and
2881:10.1088/1748-605x/abf1a8
2688:Progress in Biomaterials
2438:10.1177/0883911507082157
2260:10.3389/fbioe.2019.00342
1553:"Hydrogels: Impregnated"
1463:10.3389/fchem.2018.00449
92:Physical characteristics
52:Chemical characteristics
16:Not to be confused with
2179:10.1089/wound.2019.1018
2484:10.1002/mabi.201900123
2167:Advances in Wound Care
1854:10.1002/adfm.201100871
1594:10.1002/anbr.202100004
1530:"Hydrogels: Amorphous"
1450:Frontiers in Chemistry
259:10.1002/adma.200501612
78:antimicrobial peptides
1885:Journal of Wound Care
1316:Nature Communications
181:poly(ethylene glycol)
18:Hydrocolloid dressing
2868:Biomedical Materials
2302:J. Pract. Clin. Nurs
1016:10.3390/ijms11125152
855:Wong, Vicky (2007).
324:10.3390/biom10081169
33:extracellular matrix
2757:2016NatSR...632670S
2322:Chin. J. Tissue Eng
2227:. 14 December 2011.
2118:10.1155/2012/843025
1643:10.2147/ijn.s245743
1507:"Hydrogels: Sheets"
1390:(20): 12764–12850.
1328:2020NatCo..11.4032L
768:2010Mate....3.1420G
660:2007NIMPB.255..343V
606:10.3390/gels5010014
251:2006AdM....18.1345P
85:oxidation-reduction
2925:Medical treatments
2811:APL Bioengineering
2745:Scientific Reports
1746:. 55–57: 681–684.
1689:Burns & Trauma
1059:Acta Biomaterialia
823:10.1039/c3cc48896a
467:Acta Biomaterialia
239:Advanced Materials
2823:10.1063/1.5088801
2765:10.1038/srep32670
2388:(32): 4323–4332.
1848:(21): 4028–4034.
1225:10.1021/bm500701u
1213:Biomacromolecules
1162:(11): 2353–2360.
1118:10.1021/bm900985h
1106:Biomacromolecules
1009:(12): 5152–5164.
909:10.1002/bip.22412
817:(18): 2356–2359.
777:10.3390/ma3021420
689:Kasko, Andrea M.
423:10.1111/wrr.12125
245:(11): 1345–1360.
177:polyvinyl alcohol
2932:
2910:
2909:
2883:
2859:
2853:
2852:
2842:
2801:
2795:
2794:
2784:
2736:
2730:
2729:
2719:
2679:
2673:
2672:
2662:
2622:
2616:
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2570:
2564:
2563:
2518:
2512:
2511:
2467:
2458:
2457:
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2371:
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2310:
2309:
2297:
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2290:
2280:
2262:
2238:
2229:
2228:
2215:
2209:
2208:
2198:
2158:
2149:
2148:
2138:
2120:
2096:
2090:
2089:
2079:
2061:
2037:
2031:
2030:
2020:
1980:
1974:
1973:
1963:
1923:
1917:
1916:
1880:
1874:
1873:
1837:
1831:
1830:
1820:
1802:
1778:
1772:
1771:
1739:
1733:
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1680:
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1663:
1645:
1621:
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1614:
1596:
1572:
1563:
1562:
1549:
1540:
1539:
1526:
1517:
1516:
1503:
1494:
1493:
1483:
1465:
1441:
1426:
1425:
1415:
1384:Chemical Reviews
1375:
1366:
1365:
1355:
1307:
1301:
1300:
1264:
1255:
1254:
1244:
1219:(8): 2861–2869.
1204:
1198:
1197:
1187:
1147:
1138:
1137:
1100:
1091:
1090:
1053:
1047:
1046:
1036:
1018:
994:
988:
987:
969:
960:(9): 1184–1202.
945:
939:
938:
928:
888:
871:
870:
852:
843:
842:
806:
800:
799:
797:
779:
762:(2): 1420–1460.
747:
738:
737:
701:
695:
694:
686:
680:
679:
643:
637:
636:
626:
608:
584:
573:
572:
544:
535:
534:
514:
501:
500:
490:
458:
452:
451:
425:
401:
395:
394:
392:
368:
355:
354:
344:
326:
302:
279:
278:
234:
2940:
2939:
2935:
2934:
2933:
2931:
2930:
2929:
2915:
2914:
2913:
2861:
2860:
2856:
2803:
2802:
2798:
2738:
2737:
2733:
2681:
2680:
2676:
2624:
2623:
2619:
2572:
2571:
2567:
2520:
2519:
2515:
2469:
2468:
2461:
2422:
2421:
2417:
2379:
2378:
2374:
2363:J. Yangtze Univ
2360:
2359:
2355:
2339:
2338:
2334:
2318:
2317:
2313:
2299:
2298:
2294:
2240:
2239:
2232:
2217:
2216:
2212:
2160:
2159:
2152:
2098:
2097:
2093:
2039:
2038:
2034:
1995:(6): CD012583.
1982:
1981:
1977:
1938:(7): CD009101.
1925:
1924:
1920:
1882:
1881:
1877:
1839:
1838:
1834:
1780:
1779:
1775:
1741:
1740:
1736:
1682:
1681:
1677:
1623:
1622:
1618:
1574:
1573:
1566:
1551:
1550:
1543:
1528:
1527:
1520:
1505:
1504:
1497:
1443:
1442:
1429:
1377:
1376:
1369:
1309:
1308:
1304:
1266:
1265:
1258:
1206:
1205:
1201:
1149:
1148:
1141:
1102:
1101:
1094:
1055:
1054:
1050:
996:
995:
991:
947:
946:
942:
890:
889:
874:
854:
853:
846:
808:
807:
803:
749:
748:
741:
703:
702:
698:
688:
687:
683:
645:
644:
640:
586:
585:
576:
546:
545:
538:
516:
515:
504:
460:
459:
455:
403:
402:
398:
377:Materials Today
370:
369:
358:
304:
303:
282:
236:
235:
210:
206:
197:
173:
137:hyaluronic acid
133:
128:
119:
111:
94:
54:
49:
47:Characteristics
21:
12:
11:
5:
2938:
2936:
2928:
2927:
2917:
2916:
2912:
2911:
2854:
2796:
2731:
2674:
2637:(3): 217–233.
2617:
2565:
2513:
2478:(8): 1900123.
2459:
2432:(5): 525–538.
2415:
2372:
2353:
2332:
2311:
2292:
2230:
2210:
2150:
2091:
2032:
1975:
1918:
1891:(3): 133–136.
1875:
1832:
1787:Bioengineering
1773:
1734:
1675:
1616:
1587:(6): 2100004.
1564:
1541:
1518:
1495:
1427:
1367:
1302:
1269:Macromolecules
1256:
1199:
1139:
1112:(1): 133–142.
1092:
1065:(2): 882–891.
1048:
989:
940:
903:(6): 637–644.
872:
844:
801:
739:
696:
681:
654:(2): 343–349.
638:
574:
555:(2): 127–136.
536:
502:
453:
416:(2): 174–186.
396:
356:
280:
207:
205:
202:
196:
193:
172:
169:
132:
129:
127:
124:
118:
115:
110:
107:
93:
90:
53:
50:
48:
45:
13:
10:
9:
6:
4:
3:
2:
2937:
2926:
2923:
2922:
2920:
2907:
2903:
2899:
2895:
2891:
2887:
2882:
2877:
2874:(4): 045013.
2873:
2869:
2865:
2858:
2855:
2850:
2846:
2841:
2836:
2832:
2828:
2824:
2820:
2817:(2): 026102.
2816:
2812:
2808:
2800:
2797:
2792:
2788:
2783:
2778:
2774:
2770:
2766:
2762:
2758:
2754:
2750:
2746:
2742:
2735:
2732:
2727:
2723:
2718:
2713:
2709:
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2701:
2697:
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2689:
2685:
2678:
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2609:
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2597:
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2493:
2489:
2485:
2481:
2477:
2473:
2466:
2464:
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2447:
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2303:
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2293:
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2279:
2274:
2270:
2266:
2261:
2256:
2252:
2248:
2244:
2237:
2235:
2231:
2226:
2225:
2224:Science Daily
2220:
2214:
2211:
2206:
2202:
2197:
2192:
2188:
2184:
2180:
2176:
2172:
2168:
2164:
2157:
2155:
2151:
2146:
2142:
2137:
2132:
2128:
2124:
2119:
2114:
2110:
2106:
2102:
2095:
2092:
2087:
2083:
2078:
2073:
2069:
2065:
2060:
2055:
2051:
2047:
2043:
2036:
2033:
2028:
2024:
2019:
2014:
2010:
2006:
2002:
1998:
1994:
1990:
1986:
1979:
1976:
1971:
1967:
1962:
1957:
1953:
1949:
1945:
1941:
1937:
1933:
1929:
1922:
1919:
1914:
1910:
1906:
1902:
1898:
1894:
1890:
1886:
1879:
1876:
1871:
1867:
1863:
1859:
1855:
1851:
1847:
1843:
1836:
1833:
1828:
1824:
1819:
1814:
1810:
1806:
1801:
1796:
1792:
1788:
1784:
1777:
1774:
1769:
1765:
1761:
1757:
1753:
1749:
1745:
1738:
1735:
1730:
1726:
1721:
1716:
1712:
1708:
1703:
1698:
1694:
1690:
1686:
1679:
1676:
1671:
1667:
1662:
1657:
1653:
1649:
1644:
1639:
1636:: 3887–3901.
1635:
1631:
1627:
1620:
1617:
1612:
1608:
1604:
1600:
1595:
1590:
1586:
1582:
1578:
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1569:
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1560:
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1525:
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1500:
1496:
1491:
1487:
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1423:
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1401:
1397:
1393:
1389:
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1381:
1374:
1372:
1368:
1363:
1359:
1354:
1349:
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1303:
1298:
1294:
1290:
1286:
1282:
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1270:
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1252:
1248:
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1234:
1230:
1226:
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1203:
1200:
1195:
1191:
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1177:
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1169:
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1146:
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1127:
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1093:
1088:
1084:
1080:
1076:
1072:
1068:
1064:
1060:
1052:
1049:
1044:
1040:
1035:
1030:
1026:
1022:
1017:
1012:
1008:
1004:
1000:
993:
990:
985:
981:
977:
973:
968:
963:
959:
955:
951:
944:
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936:
932:
927:
922:
918:
914:
910:
906:
902:
898:
894:
887:
885:
883:
881:
879:
877:
873:
868:
864:
863:
858:
851:
849:
845:
840:
836:
832:
828:
824:
820:
816:
812:
805:
802:
796:
791:
787:
783:
778:
773:
769:
765:
761:
757:
753:
746:
744:
740:
735:
731:
727:
723:
719:
715:
711:
707:
700:
697:
692:
685:
682:
677:
673:
669:
665:
661:
657:
653:
649:
642:
639:
634:
630:
625:
620:
616:
612:
607:
602:
598:
594:
590:
583:
581:
579:
575:
570:
566:
562:
558:
554:
550:
543:
541:
537:
532:
528:
524:
520:
513:
511:
509:
507:
503:
498:
494:
489:
484:
480:
476:
472:
468:
464:
457:
454:
449:
445:
441:
437:
433:
429:
424:
419:
415:
411:
407:
400:
397:
391:
386:
382:
378:
374:
367:
365:
363:
361:
357:
352:
348:
343:
338:
334:
330:
325:
320:
316:
312:
308:
301:
299:
297:
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293:
291:
289:
287:
285:
281:
276:
272:
268:
264:
260:
256:
252:
248:
244:
240:
233:
231:
229:
227:
225:
223:
221:
219:
217:
215:
213:
209:
203:
201:
194:
192:
190:
186:
182:
178:
170:
168:
166:
162:
158:
154:
150:
146:
142:
138:
130:
125:
123:
116:
114:
108:
106:
102:
98:
91:
89:
86:
81:
79:
74:
70:
67:
66:Self-assembly
61:
59:
58:cross-linking
51:
46:
44:
41:
36:
34:
28:
25:
19:
2871:
2867:
2857:
2814:
2810:
2799:
2751:(1): 32670.
2748:
2744:
2734:
2691:
2687:
2677:
2634:
2630:
2620:
2579:
2575:
2568:
2527:
2523:
2516:
2475:
2471:
2429:
2425:
2418:
2385:
2382:Biomaterials
2381:
2375:
2366:
2362:
2356:
2350:: 1811–1813.
2347:
2341:
2335:
2329:: 2659–2662.
2326:
2320:
2314:
2305:
2301:
2295:
2250:
2246:
2222:
2213:
2173:(2): 48–60.
2170:
2166:
2108:
2104:
2094:
2049:
2045:
2035:
1992:
1988:
1978:
1935:
1931:
1921:
1888:
1884:
1878:
1845:
1841:
1835:
1790:
1786:
1776:
1743:
1737:
1692:
1688:
1678:
1633:
1629:
1619:
1584:
1580:
1558:Wound Source
1556:
1535:Wound Source
1533:
1512:Wound Source
1510:
1453:
1449:
1387:
1383:
1319:
1315:
1305:
1275:(1): 72–80.
1272:
1268:
1216:
1212:
1202:
1159:
1155:
1109:
1105:
1062:
1058:
1051:
1006:
1002:
992:
957:
953:
943:
900:
896:
860:
814:
811:Chem. Commun
810:
804:
759:
755:
712:(1): 13–36.
709:
705:
699:
684:
651:
647:
641:
596:
592:
552:
548:
522:
518:
470:
466:
456:
413:
409:
399:
383:(4): 40–48.
380:
376:
314:
311:Biomolecules
310:
242:
238:
198:
185:polyurethane
174:
134:
120:
117:Applications
112:
103:
99:
95:
82:
75:
71:
62:
55:
37:
29:
22:
2694:(1): 1–21.
2582:: 487–498.
1322:(1): 4032.
897:Biopolymers
857:"Hydrogels"
317:(8): 1169.
189:3D printing
2530:: 110837.
2111:: 843025.
2052:: 740863.
525:: S1–S11.
204:References
40:nanofibers
2906:232355932
2890:1748-6041
2831:2473-2877
2773:2045-2322
2708:2194-0509
2651:2090-1232
2612:108904004
2596:0928-4931
2560:215750261
2544:0928-4931
2508:195355185
2492:1616-5187
2446:0883-9115
2402:0142-9612
2343:Huaxi Med
2308:: 91–100.
2269:2296-4185
2187:2162-1918
2127:1741-427X
2068:2296-4185
2009:1465-1858
1952:1465-1858
1905:0969-0700
1862:1616-301X
1809:2306-5354
1793:(6): 79.
1768:136738274
1760:1662-8985
1711:2321-3876
1652:1178-2013
1611:233669658
1603:2699-9307
1472:2296-2646
1404:0009-2665
1344:2041-1723
1297:104431319
1289:0024-9297
1233:1525-7797
1176:0957-4530
1126:1525-7797
1079:1742-7061
1025:1422-0067
976:0005-2736
917:0006-3525
831:1359-7345
786:1996-1944
756:Materials
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