Sequestration of harmful proteases as human neutrophil elastase (HNE) from the chronic wound environment is an important goal of wound dressing design and function. Monosaccharides attached to cellulose conjugates as ester-appended aldohexoses and ketohexoses were prepared on cotton gauze as monosccharide-citrate-cellulose-esters for HNE sequestration. The monosaccharide-cellulose analogs demonstrated selective binding when the derivatized cotton dressings were measured for sequestration of HNE. Each monosaccharide-cellulose conjugate was prepared as a cellulose citrate-linked monosaccharide ester on the cotton wound dressing, and assayed under wound exudate-mimicked conditions for elastase sequestration activity. A series of three aldohexose and four ketohexose ester cellulose conjugates were prepared on cotton gauze through citric acid-cellulose cross linking esterification. The monosaccharide portion of the conjugate was characterized by hydrolysis of the citrate-monosaccharide ester bond, and subsequent analysis of the free monosaccharide with high performance anion exchange chromatography. The ketohexose and aldohexose conjugate levels on cotton were quantified on cotton using chromatography and found to be present in milligram/gram amounts. The citrate-cellulose ester bonds were characterized with FTIR. Ketohexose-citrate-cellulose conjugates sequestered more elastase activity than aldohexose-citrate-cellulose conjugates. The monosaccharide cellulose conjugate families each gave distinctive profiles in elastase-lowering effects. Possible mechanisms of elastase binding to the monosaccharide-cellulose conjugates are discussed.
Miraftab, M.; Qlao, Q.; Kennedy, J.F.; Anand, S.C.; Groocock, M.R. Fibres for wound dressings based on mixed carbohydrate polymer fibres. Carbohydr. Polym. 2003, 53, 225–231, doi:10.1016/S0144-8617(03)00108-5.
[4]
Van der Weyden, E.A. Treatment of a venous leg ulcer with a honey alginate dressing. Br. J. Community Nurs. 2005, 10, S21–S27.
[5]
Kirker, K.R.; Luo, Y.; Nielson, J.H.; Shelby, J.; Prestweich, G.D. Glycosaminoglycan hydrogel films as bio-interactive dressings for wound healing. Biomaterials 2002, 23, 3661–3671, doi:10.1016/S0142-9612(02)00100-X.
[6]
Garg, T.; Singh, O.; Arora, S.; Murthy, R.S.R. Scaffold: A novel carrier for cell and drug delivery. Crit. Rev. Ther. Drug Carrier Syst. 2012, 29, 1–63, doi:10.1615/CritRevTherDrugCarrierSyst.v29.i1.10.
[7]
Voigt, J.; Driver, V.R. Hyaluronic acid derivatives and their healing effect on burns, epithelial surgical wounds, and chronic wounds: A systematic review and meta-analysis of randomized controlled trials. Wound Repair Regen. 2012, 20, 317–331, doi:10.1111/j.1524-475X.2012.00777.x.
[8]
Edwards, J.V. Future Structure and Properties of Mechanism-Based Wound Dressings. In Modified Fibers with Medical and Specialty Applications; Edwards, J.V., Buschle-Diller, G., Goheen, S.C., Eds.; Springer: Dordrecht, The Netherlands, 2006; pp. 11–33.
[9]
Delatte, S.J.; Evans, J.; Hebra, A.; Adamson, W.; Othersen, H.B.; Tagge, E.P.; Hardin, W.; Priebe, C.; Winthrop, A. Effectiveness of beta-glucan collagen for treatment of partial-thickness burns in children. J. Pediatr. Surg. 2001, 36, 113–118, doi:10.1053/jpsu.2001.20024.
[10]
Rathinamoorthy, R.; Sasikala, L. Polysaccharide fibers in wound management. Int. J. Pharm. Pharm. Sci. 2011, 3, 38–44.
[11]
Backdahl, H.; Helenlus, G.; Bodin, A.; Nannmark, U.; Johansson, B.R.; Risber, B.; Gatenholm, P. Mechanical properties of bacterial cellulose and interactions with smooth muscle cells. Biomaterials 2006, 27, 2141–2149.
[12]
Wiegand, C.; Elsner, P.; Hipler, U.-C.; Klemm, D. Protease and ROS activities influenced by a composite of bacterial cellulose and collagen type I in vitro. Cellulose 2006, 13, 689–696, doi:10.1007/s10570-006-9073-0.
[13]
Cullen, B.; Smith, R.; McCulloch, E.; Silcock, D.; Morrison, L. Mechanism of action of PROMOGRAN, a protease modulating matrix, for the treatment of diabetic foot ulcers. Wound Repair Regen. 2002, 10, 16–25, doi:10.1046/j.1524-475X.2002.10703.x.
[14]
Szczesniak, M.; Kubis, A. The influence of hydrophilizing agents on gel formation rate of cellulose derivatives. Part 3: Effect of hydrophilizing agents and of polymer type on the release rate of hydrocortisone form xerogel dressing. Pharmazie 1993, 48, 926–927.
Wollina, U.; Abdel-Naser, M.B.; Verma, S. Skin physiology and textiles – Consideratoin of basic interactions. Curr. Probl. Dermatol. 2006, 33, 1–16, doi:10.1159/000093926.
[17]
Thomas, S. Wound Management and Dressings; The Pharmaceutical Press: London, UK, 1990; pp. 1–197.
[18]
Hashimoto, T.; Suzuki, Y.; Tanihara, M.; Kakimaru, Y.; Suzuki, K. Development of alginate wound dressings with hybrid peptides derived from lamin and elastin. Biomaterials 2004, 25, 1407–1414, doi:10.1016/j.biomaterials.2003.07.004.
[19]
Edwards, J.V.; Bopp, A.F.; Batiste, S.L.; Goynes, W.R. Human Neutrophil Elastase Innhibition with a Novel Cotton-Alginate Wound Dressing Formulation. J. Biomed. Mater. Res. Part A 2003, 66, 433–440.
[20]
Dumville, J.C.; Deshpande, S.; O’Meara, S.; Speak, K. Alginate dressings for healing diabetic foot ulcers. Chochrane Database of Syst. Rev. 2012, 2, doi:10.1002/14651858.CD009110.pub2.
[21]
Kato, Y.; Onishi, H.; Machida, Y. Application of chitin and chitosan derivatives in the pharmaceutical field. Curr. Pharm. Biotechnol. 2003, 4, 303–309, doi:10.2174/1389201033489748.
[22]
Jayakumar, R.; Prabaharan, M.; Sudheesh Kumar, P.T.; Nair, S.V.; Tamura, H. Biomaterials based on chitin and chitosan in wound dressing applications. Biotechnol. Adv. 2011, 29, 322–337, doi:10.1016/j.biotechadv.2011.01.005.
[23]
Madhumathi, K.; Sudheesh Kumar, P.T.; Abhilash, S.; Sreeja, V.; Tamura, H.; Manzoor, K.; Nair, S.V.; Jayakumar, R. Development of novel chitin/nanosilver composite scaffolds for wound dressing applications. J. Mater. Sci: Mater. Med. 2010, 21, 807–813, doi:10.1007/s10856-009-3877-z.
Edwards, J.V.; Eggleston, G.; Yager, D.R.; Cohen, I.K.; Diegelmann, R.F.; Bopp, A.F. Design, preparation and assessment of citrate-linked monosaccharide cellulose conjugates with elastase-lowering activity. Carbohydr. Polym. 2002, 50, 305–314, doi:10.1016/S0144-8617(02)00029-2.
[29]
Edwards, J.V.; Howley, P.S. Human neutrophil elastase and collagenase sequestration with phosphorylated cotton wound dressings. J. Biomed. Mater. Res. Part A 2007, 82, 446–454, doi:10.1002/jbm.a.31171.
[30]
Yager, D.; Nwomeh, B. The proteolytic environment of chronic wounds. Wound Repair Regen. 1999, 7, 433–441, doi:10.1046/j.1524-475X.1999.00433.x.
[31]
Barros, S.C.; Martins, J.A.; Marcos, J.C.; Cavaco-Paulo, A. Characterization of potential elastase inhibitor-peptides regulated by a molecular switch for wound dressing applications. Enzyme Microb. Technol. 2012, 50, 107–114, doi:10.1016/j.enzmictec.2011.10.006.
[32]
Edwards, J.V.; Batiste, S.L.; Gibbins, E.M.; Goheen, S.C. Synthesis and activity of NH2- and COOH-terminal elastase recognition sequences on cotton. J. Pept. Res. 1999, 54, 536–543, doi:10.1034/j.1399-3011.1999.00134.x.
[33]
Wiegand, C.; Abel, M.; Ruth, P.; Hipler, U.C. Superabsorbent polymer-containing wound dressings have a beneficial effect on wound healing by reducing PMN elastase concentration and inhibiting microbial growth. J. Mater. Sci. Mater. Med. 2011, 22, 2583–2590, doi:10.1007/s10856-011-4423-3.
[34]
Meyer-Ingold, W.; Eichner, W.; Ettner, N.; Schink, M. Wound coverings for removal of interfering factors from wound fluid. U.S. Patent 6156334, 5 December 2000.
[35]
Rayment, E.A.; Dargaville, T.R.; Shooter, G.K.; George, G.A.; Upton, Z. Attenuation of protease activity in chronic wound fluid with bisphosphonate-functionalised hydrogels. Biomaterials 2008, 29, 1785–1795.
[36]
Vachon, D.J.; Yager, D.R. Novel sulfonated hydrogel composite with the ability to inhibit proteases and bacterial growth. J Biomed. Mater. Res. Part A 2006, 76, 35–43, doi:10.1002/jbm.a.30440.
[37]
Eming, S.A.; Smola-Hess, S.; Kurschat, P.; Hirche, D.; Krieg, T.; Smola, H. A novel property of povidon-iodine: Inhibition of excessive protease levels in chronic non-healing wounds. J. Investig. Dermatol. 2006, 126, 2731–2733, doi:10.1038/sj.jid.5700474.
[38]
Edwards, J.V.; Bopp, A.F.; Batiste, S.; Ullah, A.J.; Cohen, I.K.; Diegelmann, R.F.; Montante, S.J. Inhibition of elastase by a synthetic cotton-bound serine protease inhibitor: In vitro kinetics and inhibitor release. Wound Repair Regen. 1999, 7, 106–108.
[39]
Edwards, J.V.; Howley, P.; Davis, R.; Mashchak, A.; Goheen, S.C. Protease inhibition by oleic acid transfer from chronic wound dressing to albumin. Int. J. Pharm. 2007, 340, 42–51, doi:10.1016/j.ijpharm.2007.03.018.
[40]
Wright, J.B.; Lam, K.; Buret, A.G.; Olson, M.E.; Burrell, R.E. Early healing events in a procine model of contaminated wounds: effects of nanocrystalline silver on matrix metalloproteinases, cell apoptosis, and healing. Wound Repair Regen. 2002, 10, 141–151, doi:10.1046/j.1524-475X.2002.10308.x.
[41]
Adhiraan, N.; Shanmugasundaram, N.; Babu, M. Gelatin microspheres cross-linked with EDC as a drug delivery system for doxycyline: development and characterization. J. Microencapsul. 2007, 24, 659–671, doi:10.1080/02652040701500137.
[42]
Yang, C.Q. Characterizing ester crosslinkages in cotton cellulose with FT-IR photoacoustic spectroscopy. Text. Res. J. 1991, 61, 298–305, doi:10.1177/004051759106100509.
[43]
Bode, W.; Wei, A.-Z.; Huber, R.; Meyer, E.; Travis, J.; Neumann, S. X-ray crystal structure of the complex of human leukocyte elastase (PMN elastase) and the third domain of the turkey ovomucoid inhibitor. EMBO J. 1986, 5, 2453–2458.
[44]
He, X.-P.; Wang, X.-W.; Jin, X.-P.; Zhou, H.; Shi, X.-X.; Chen, G.-R.; Long, Y.-T. Epimeric monosaccharide-quinone hybrids on gold electrodes toward the electrochemical probing of specific carbohydrate-protein recognitions. J. Am. Chem. Soc. 2011, 133, 3649–3657.
[45]
Toone, E.J. Structure and energetics of protein carbohydrate complexes. Curr. Opin. Struct. Biol. 1994, 4, 719–728, doi:10.1016/S0959-440X(94)90170-8.
[46]
Ledl, F.; Schleicher, E. New aspects of the Maillard reaction in foods and in the human body. Angew. Chem. 1990, 29, 565–594, doi:10.1002/anie.199005653.
[47]
Blow, D.M. Structure and Mechanism of Chymotrypsin. Acc. Chem. Res. 1976, 9, 145–152, doi:10.1021/ar50100a004.
[48]
Bode, W.; Meyer, E.; Powers, J.C. Human leukocyte and porcine pancreatic elastase: X-ray crystal structures, mechanism, substrate specificity and mechanism-based inhibitors. Biochemistry 1989, 28, 1951–1963, doi:10.1021/bi00431a001.
[49]
Levit, D.A.S.; Schechter, I.; Berger, A. On the active site of elastase: Partial mapping by means of specific peptide substrates. FEBS Lett. 1970, 11, 281–283, doi:10.1016/0014-5793(70)80548-8.
[50]
Ying, Q.L.; Rinehart, A.R.; Simon, S.R.; Cheronis, J.C. Inhibition of human leucocyte elastase by ursolic acid. Evidence for a binding site for pentacyclic triterpenes. Biochem. J. 1991, 277, 521–526.
[51]
Meyer, E.F.; Clore, G.M.; Gronenborn, A.M.; Hansen, H.A.S. Analysis of an enzyme substrate complex. Biochemistry 1988, 27, 725–730.
