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BOARD MEMBER

Professor Dr. Esther Middelkoop

Association of Dutch Burn Centres PO Box 1015 1940 EA Beverwijk The Netherlands

Curriculum

Professor Dr. Esther Middelkoop studied chemistry at the University of Utrecht, and obtained a PhD in biochemistry in 1989. During some years she worked as post-doc at the biochemistry department of the University of Amsterdam, in the Academic Medical Centre. In 1992 she started her work on skin replacement materials at the department of dermatology of the AMC. In 1996 she continued this work at the Burn Centre of the Red Cross Hospital in Beverwijk and with the Dutch Burns Foundation. She initiated several studies in the field of skin substitutes, wound healing and scar treatment, which lead a.o. to some 7 PhD-theses. Internationally, Esther Middelkoop participates actively in the European Tissue Repair Society (president 2003-2004). Since January 2004, the research activities of the three dutch burn centers are combined in the Association of Dutch Burn Centres. Esther Middelkoop is the research director of the organization. Since September 2006, she is also professor in Skin Regeneration and Wound Healing at the dept. of Plastic, Reconstructive and Hand Surgery of the Free University Medical Centre in Amsterdam.

Publications (not including abstracts) Roelofsen, B., Sanderink, G., Middelkoop, E., Hamer, R. and Op den Kamp, J.A.F. (1984) Murine erythrocytes contain high levels of lysophospholipase activity. Biochim. Biophys. Acta 792, 99-102. 2 Middelkoop, E., Lubin, B.H., Op den Kamp, J.A.F. and Roelofsen, B. (1986) Flipflop rates of individual molecular species of phosphatidylcholine in the human red cell membrane. Biochim. Biophys. Acta 855, 421-424. 3 Middelkoop, E., Lubin, B.H., Bevers, E.M., Op den Kamp, J.A.F., Comfurius, P., Chiu, D.T.-Y., Zwaal, R.F.A., van Deenen, L.L.M. and Roelofsen, B. (1988) Studies on sickled erythrocytes provide evidence that the asymmetric distribution of phosphatidylserine in the red cell membrane is maintained by both ATPdependent translocation and interaction with membrane skeletal proteins. Biochim. Biophys. Acta 937, 281-288. 4 Middelkoop, E., Coppens, A., Llanillo, M., van der Hoek, E.E., Slotboom, A.J., Lubin, B.H., Op den Kamp, J.A.F., van Deenen, L.L.M. and Roelofsen, B. (1989) Aminophospholipid translocase in the plasma membrane of Friend erythroleukemic cells can induce an asymmetric topology for phosphatidylserine but not for phosphatidylethanolamine. Biochim. Biophys. Acta 978, 241-248. 5 Middelkoop, E., van der Hoek, E.E., Bevers, E.M., Comfurius, P., Slotboom, A.J., Op den Kamp, J.A.F., Lubin, B.H., Zwaal, R.F.A. and Roelofsen, B. (1989) Involvement of ATP-dependent aminophospholipid translocation in maintaining phospholipid asymmetry in diamide-treated human erythrocytes. Biochim. Biophys. Acta 981, 151-160. 6 Middelkoop, E. (1989) Transmembrane phospholipid asymmetry in erythroid cells: mechanisms of maintenance. Rijksuniversiteit te Utrecht, PhD-thesis. 7 Middelkoop, E., Strijland, A. and Tager, J.M. (1991) Does aminotriazole inhibit import of catalase into peroxisomes by retarding unfolding? FEBS letters 279, 7982. 8 Stuurman, N., Floore, A., Middelkoop, E., van Driel, R. and de Jong, L. (1991) A nuclear body protein shuttles between nucleus and cytoplasm. Possible involvement of nuclear bodies in RNA metabolism. University of Amsterdam, PhD-thesis, pp 87-99. 9 Wiemer, E.A.C., Ofman, R., Middelkoop, E., De Boer, M., Wanders, R.J.A. and Tager, J.M. (1992) Production and characterization of monoclonal antibodies against native and disassembled human catalase. J. Immunol. Meth. 151, 165175. 10 Herzberg, N.H., Middelkoop, E., Adorf, M., Dekker, H., van Galen, M.J.M., Bolhuis, P. and van den Bogert, C. (1992) Mitochondria in cultured human muscle cells depleted of mitochondrial DNA. University of Amsterdam, PhDthesis, pp 63-76. 11 Oude Elferink, R.P.J., Bakker, C.T.M., Roelofsen, H., Middelkoop, E., Ottenhof, R., Heijn, M. and Jansen, P.L.M. (1993) Accumulation of organic anion in intracellular 1

vesicles of cultured rat hepatocytes is mediated by the canalicular multispecific organic anion transporter. Hepatology 17, 434-444.

12 Middelkoop, E., Wiemer, E.A.C., Schoenmaker, D.E.T., Strijland, A. and Tager, J.M. (1993) Topology of catalase assembly in human skin fibroblasts. Biochim. Biophys. Acta, 1220, 15-20. 13 De Vries, H.J.C., Mekkes, J.R., Middelkoop, E., Hinrichs, W.L.J., Wildevuur, Ch.R.H. and Westerhof, W. (1993) Dermal substitutes for full thickness wounds in a one stage grafting model. Wound Rep. Regen., 1, 244-252. 14 Herzberg, N.H., Middelkoop, E., Adorf, M., Dekker, H., van Galen, M.J.M., Bolhuis, P. and van den Bogert, C. (1993) Mitochondria in cultured human muscle cells depleted of mitochondrial DNA. Eur. J. Cell Biol. 61, 400-408. 15 De Vries, H.J.C., Middelkoop, E., Mekkes, J.R., Dutrieux, R.P., Wildevuur, C.H.R., Westerhof, W. (1994) Dermal regeneration in a native non crosslinked collagen sponge with different extracellular matrix molecules. Wound Rep. Regen., 2, 37-47. 16 De Vries, H.J.C., Zeegelaar, J.E., Middelkoop, E., Gijsbers, G., van Marle, J., Wildevuur, C.H.R., Westerhof, W. (1995) Reduced wound contraction and scar formation in punch biopsy wounds. Native collagen dermal substitutes, a clinical study. Brit. J. Dermatol. 132, 690-697. 17 Middelkoop, E., De Vries, H.J.C., Ruuls, L., Everts, V., Wildevuur, C.H.R., Westerhof, W. (1995) Adherence, proliferation and collagen turnover by human fibroblasts seeded into different types of collagen sponges. Cell Tissue Res. 280, 447-453. 18 De Vries, H.J.C., Middelkoop, E., Van Heemstra-Hoen, M., Wildevuur, C.H.R., Westerhof, W. (1995) Stromal cells from subcutaneous adipose tissue seeded in a native collagen/elastin dermal substitute reduce wound contraction in full thickness skin defects. Lab. Invest. 73, 532-540. 19 Middelkoop, E. (1995) Cytokines en wondgenezing. Ned. Tijdschr. Dermatol. Venereol. 5, 300-302. 20 Roelofsen, B., Middelkoop, E., Vermeulen, W.P., Smith, A.J., Op den Kamp, J.A.F. (1996) Phospholipid flippases: neither exclusively, nor only involved in maintaining membrane phospholipid asymmetry. In: Molecular Dynamics of Biomembranes, NATO ASI series, Vol. H96, Ed. J.A.F. Op den Kamp, Springer Verlag, Berlin Heidelberg pp.367-382. 21 Lamme, E.N., de Vries, H.J.C., van Veen, H., Gabbiani, G., Westerhof, W., Middelkoop, E. (1996) Extracellular matrix characterization during healing of full thickness wounds treated with a collagen/elastin dermal substitute shows improved skin regeneration in pigs. J. Histochem. Cytochem. 44, 1311-1322. 22 Heijmen, F.H., du Pont, J.S., Middelkoop, E., Kreis, R.W., Hoekstra, M.J. (1997) The crosslinking of dermal sheep collagen with tannic acid. Biomaterials, 18, 749-754. 23 Van Baare, J, Mackie, D.P., Middelkoop, E. (1997) Letter to the editor; Burns, 23, 460. 24 Lamme, E.N., Gustafsson, T.O., Middelkoop, E. (1998) Topical sustained release of iodine stimulates epidermal regeneration in experimental full thickness wounds. Arch. Dermatol. Res. 290, 18-24.

25 Van Zuijlen, P.P.M., Westerhof, W., Kreis, R.W., Middelkoop, E. (1997) Skin substitutes: the current state of affairs. Journal of Surgical Pathology, 2, 193202. 26 Van Baare, J., Ligtvoet, E.E.J., Middelkoop, E. (1998) Microbiological evaluation of glycerolised human cadaveric skin. Transplantation, 65, 966-970. 27 Lamme, E.N., van Leeuwen, R.T.J., Jonker, A., van Marle, J., Middelkoop, E. (1998) Living skin substitutes: survival and function of fibroblasts seeded in a dermal substitute in experimental wounds. J. Invest. Dermatol. 111, 989-995. 28 Loots, M.A.M., Lamme, E.N., Zeegelaar, J., Mekkes, J.R., Bos, J.D., Middelkoop, E (1998) Differences in cellular infiltrate and extracellular matrix of chronic diabetic and venous ulcers versus acute wounds. J. Invest. Dermatol. 111, 850857. 29 Van Zuijlen, P.P.M., van Leeuwen, R.T.J., Middelkoop, E. (1998) Practical sources for autologous fibroblasts to prepare a bioengineered dermal equivalent. Letter to the editor. Burns, 24, 687. 30 Van Baare, J. Cameron, P.U., Vardaxis, N., Pagnon, J., Reece, J., Middelkoop, E., Crowe, S.M. (1998) Comparison of glycerol presservation with cryopreservation methods on HIV-1 activation. J Burn Care Rehabil. 19, 494-500. 31 Van Zuijlen, P.P.M., Van der Veen, H., Vloemans, A.F.P.M., Middelkoop, E., Kreis, R.W. (1998) De kunsthuid: toepassingen en mogelijkheden van geavanceerde huidvervangende materialen. Ned. Tijdschr. Traumatol. 6, 151158. 32 Loots, M.A.M., Lamme, E.N. Mekkes, J.R., Bos, J.D., Middelkoop, E. (1999) Cultured fibroblasts from chronic diabetic wounds on the lower extremity (noninsulin dependent diabetes mellitus) show disturbed proliferation. Arch. Dermatol. Res. 291, 93-99. 33 De Vries, H.J.C., van Zuijlen, P.P.M., Middelkoop, E., Westerhof, W. (1999) Skin substitutes and their role in the treatment of non-healing wounds. Zeitschrift für Hautkrankheiten, 11, 675-682. 34 Davidson J., Middelkoop E., Vanscheidt W. (Eds.) Collagenase in the treatment strategy for wound management. 2000, ISBN 3-540-67542-6 Springer-Verlag Berlin Heidelberg New York 35 Lamme, E.N., Van Leeuwen, R.T.J., Brandsma, K., Van Marle, J., Middelkoop, E. (2000) Higher numbers of autologous fibroblasts in an artificial dermal substitute improve tissue regeneration and modulate scar tissue formation. J. Pathol. 190, 595-603. 36 Van Zuijlen, P.P.M., Van Trier, A.J.M., Vloemans, A.F.P.M., Groenevelt, F., Kreis, R.W., Middelkoop, E. (2000) Graft survival and effectiveness of dermal substitution in burns and reconstructive surgery in a one-stage grafting model. Plast. Rec. Surg. 106, 615-623. 37 Vloemans, A.F.P.M., Soesman, A.M., Kreis, R.W., Middelkoop, E. (2001) A newly developed hydrofibre dressing in the treatment of partial thickness burns. Burns, 27, 167-173. 38 Van Lange, J.W.L., de Roo, K., Middelkoop, E., van den Bos, T., Everts, V., Nolst Trenité, G.J. (2001) Perichondrium-wrapped collagenous matrices to induce chondroneogenesis; an in vitro study. Arch. Facial Plast. Surg. 3, 122-126.

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Westerhof, W., Das, P.K., Middelkoop, E., Verschoor, J., Storey, L., Regnier, C. (2001) Mucopolysaccharides from psyllium involved in wound healing. Drugs Exp. Clin. Res. 27 (5-6), 165-175. van Zuijlen PPM, Vloemans AFPM, van Trier AJM, Suijker MH, van Unen E, Groenevelt F, Kreis RW, Middelkoop E. (2001) Dermal substitution in acute burns and reconstructive surgery: a subjective and objective long term followup. Plast. Rec. Surg. 108, 1938-1946. van Zuijlen PPM, Lamme EN, van Galen WJM, van Galen J, Kreis RW, Middelkoop E. (2002) Long term results of a clinical trial on dermal substitution. A light microscopy and Fourier analysis based evaluation. Burns, 28, 151-160. van Zuijlen PPM, Angeles AP, Kreis RW, Bos KE, Middelkoop E. (2002) Practical suitability of scar assessment tools: implications for current research. Plast. Rec. Surg. 109, 1108-1122. Kreis, B.E., Middelkoop, E., Vloemans, A.F.P.M., Kreis, R.W. (2002) The use of a PEG tube in a burn centre. Burns, 28, 191-197. Van den Bogaerdt, A.J., van Zuijlen, P.P.M., van Galen, M.J.M., Lamme, E.N., Middelkoop, E. (2002) The suitability of cells from different tissues to be used in tissue engineered skin substitutes. Arch. Dermatol. Res. 294, 135-142. Lamme, E.N., van Leeuwen, R.T.J., Mekkes, J.R., Middelkoop, E. (2002) Allogeneic fibroblasts in dermal substitution induce inflammatory responses and interfere with dermal tissue regeneration. Wound Repair and Regeneration, 10(3), 152-160. Loots, M.A.M., Kenter, S.B., Au, F.L., van Galen, W.J.M., Middelkoop, E., Bos, J.D., Mekkes, J.R. (2002) Fibroblasts derived from chronic diabetic ulcers differ in their response to stimulation with EGF, IGF-I, bFGF and PDGF-AB compared to controls. Eur. J. Cell Biol. 81(3), 153-160. Moerman, E., Middelkoop, E., Mackie, D.P., Groenevelt, F. (2002) The temporary use of glycerol-preserved allograft for complicated wounds in plastic surgery. Burns 28, suppl.1:13. Vloemans, A.F.P.M., Schreinemachers, M.C.J.M., Middelkoop, E., Kreis, R.W. (2002) Inventory on the use of glycerol-preserved allografts in the Beverwijk Burn Centre, a retrospective study. Burns 28 Suppl.1:2. Vloemans, A.F.P.M., Middelkoop, E., Kreis, R.W. (2002) A historical appraisal of the use of cryopreserved and glycerol preserved allograft skin in the treatment of partial thickness burns. Burns 28 suppl.1:16. Van Zuijlen, P.P.M., de Vries, H.J.C., Lamme, E.N., Coppens, J.E., van Marle, J, Kreis, R.W., Middelkoop,E. (2002) Reliability of collagen orientation assessment by observers and Fourier analysis. J. Pathol. 198 (3), 284-291. van Zuijlen PP, Ruurda JJ, van Veen HA, van Marle J, van Trier AJ, Groenevelt F, Kreis RW, Middelkoop E. Collagen morphology in human skin and scar tissue: no adaptations in response to mechanical loading at joints. Burns. 2003 Aug;29(5):423-31. Vloemans AF, Soesman AM, Suijker M, Kreis RW, Middelkoop E. (2003) A randomised clinical trial comparing a hydrocolloid-derived dressing and glycerol preserved allograft skin in the management of partial thickness burns. Burns. Nov;29(7):702-10.

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Middelkoop E, van den Bogaerdt AJ, Lamme EN, Hoekstra MJ, Brandsma K, Ulrich MM. (2004) Porcine wound models for skin substitution and burn treatment. Biomaterials. Apr;25(9):1559-67. Van den Bogaerdt AJ, El Ghalbzouri A, Hensbergen PJ, Reijnen L, Verkerk M, Kroon-Smits M, Middelkoop E, Ulrich MWW. (2004) Differential expression of CRABP-II in fibroblasts derived from dermis and subcutaneous fat. Biochem Biophys Res Commun. 315 (2): 428-433. Draaijers LJ, Botman YAM, Tempelman FSH, Middelkoop E, Kreis RW, van Zuijlen PPM. Skin elasticity meter or subjective evaluation in scars: a reliability assessment. Burns, 2004 Mar;30(2):109-14. Draaijers LJ, Tempelman FSH, Botman YAM, Middelkoop E, Kreis RW, van Zuijlen PPM. Colour evaluation in scars: tristimulus colorimeter, narrow-band simple reflectance meter or subjective evaluation? Burns. 2004 Mar;30(2):103-7. Van den Bogaerdt AJ, Ulrich MWW, van Galen MJM, Reijnen L, Verkerk M, Pieper J, Lamme EN, Middelkoop E. Upside-down transfer of porcine keratinocytes from a porous, synthetic dressing to experimental full-thickness wounds. Wound Repair Regen. 2004 Mar-Apr;12(2):225-34. Draaijers LJ, Tempelman FSH, Botman YAM, Middelkoop E, Kreis RW, Tuinebreijer WE, van Zuijlen PPM. The Patient and Observer Scar Assessment Scale (POSAS): a reliable and feasible tool for scar evaluation. Plast. Rec. Surg. Plas Recon Surg 2004;113(7):1960-65 Discussed by Thomas A. Mustoe, Plast Recon Surg 2004;113:1966-1967

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Publications - continued Tempelman FSH, Vloemans AFPM, Middelkoop E, Kreis RW. The Meek-Wall micrograft technique in combination with glycerolised allografts for the treatment of extensive full thickness burns. In: Surgery in wounds. Eds: Téot L, Ziegler U, Banwell P. Springer Germany. 2004; p415-422. Van Zuijlen PPM, Suijker MH, van Trier AJM, Groenevelt, F., Kreis RW, Middelkoop, E. Scar contraction in humans: long term evaluation and prognostic factors. Int J Wounds Low Extrem 2004;3(1):7-11 Middelkoop E. Tissue Engineering: its relevance for modern healthcare. Healthcare Management 2004:September;44-46 Slot van der AJ, Zuurmond AM, Van den Bogaerdt AJ, Ulrich MM, Middelkoop E, Boers W, Karel Ronday H, De Groot J, Huizinga TW, Bank RA. Increased formation of pyridinoline cross-links due to higher telopeptide lysyl hydroxylase levels is a general fibrotic phenomenon. Matrix Biol 2004; 23:251-7 Middelkoop E. Fibroblast phenotypes and their relevance for wound healing. Int J Low Extrem Wounds. 2005 Mar;4(1):9-11 Middelkoop E. News from the laboratory of.... European Tissue Repair Society Bulletin 2006; 13(1 and 2): 15-17 Welling L, Dijkgraaf MGW, Nieuwenhuis MK, Oen IMMH, Henny CP, Middelkoop E, Luitse JSK, Gouma DJ. Impact of modification of burn centre referral criteria on primary patient outcome. J Burn Care & Research 2006; 27(6): 854-858 Coolen NA, Verkerk M, Reijnen L, Vlig M, Bogaerdt van den AJ, Breetveld M, Gibbs S, Middelkoop E, Ulrich MMW. Culture of keratinocytes for transplantation without the need of feeder layer cells. Cell Transplantation The Regenerative Medicine Journal 2007; 16(6): 649-661 Duc le Q, Breetveld M, Middelkoop E, Scheper RJ, Ulrich MMW, Gibbs S. A cytotoxic analysis of antiseptic medication on skin substitutes and autograft. British J of Derm 2007; 157: 33-40 Jong de AEE, Middelkoop E, Faber AW, Loey van NEE. Non-pharmacological nursing interventions for procedural pain relief in adults with burns: a systematic literature review. Burns Nov 2007; 33(7): 811-827 Loey van NEE, Bremer M, Faber AW, Middelkoop E, Nieuwenhuis MK. Itching following burns: epidemiology and predictors. British J of Derm Jan 2008; 158(1): 95-100; Epub 2007; Nov 6:1-6 Ulrich MMW, Verkerk M, Reijnen L, Vlig M, Bogaerdt van den AJ, Middelkoop E. Expression profile of proteins involved in scar formation in the healing process of full-thickness excisional wounds in the porcine model. Wound Repair and Regeneration 2007 Jul-Aug; 15(4): 482-490

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