Mittermayr Rainer, Branski Ludwik, Moritz Martina, Jeschke Marc G, Herndon David N, Traber Daniel, Schense Jason, Gampfer Jörg, Goppelt Andreas, Redl Heinz
Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Austrian Cluster for Tissue Regeneration, Vienna, Austria.
Shriner's Hospital for Children, University of Texas Medical Branch, Galveston, TX, USA.
J Tissue Eng Regen Med. 2016 May;10(5):E275-85. doi: 10.1002/term.1749. Epub 2013 May 31.
Controlled delivery of growth factors from biodegradable biomatrices could accelerate and improve impaired wound healing. The study aim was to determine whether platelet-derived growth factor AB (PDGF.AB) with a transglutaminase (TG) crosslinking substrate site released from a fibrin biomatrix improves wound healing in severe thermal injury. The binding and release kinetics of TG-PDGF.AB were determined in vitro. Third-degree contact burns (dorsum of Yorkshire pigs) underwent epifascial necrosectomy 24 h post-burn. Wound sites were covered with autologous meshed (3:1) split-thickness skin autografts and either secured with staples or attached with sprayed fibrin sealant (FS; n = 8/group). TG-PDGF.AB binds to the fibrin biomatrix using the TG activity of factor XIIIa, and is subsequently released through enzymatic cleavage. Three doses of TG-PDGF.AB in FS (100 ng, 1 µg and 11 µg/ml FS) were tested. TG-PDGF.AB was bound to the fibrin biomatrix as evidenced by western blot analysis and subsequently released by enzymatic cleavage. A significantly accelerated and improved wound healing was achieved using sprayed FS containing TG-PDGF.AB compared to staples alone. Low concentrations (100 ng-1 µg TG-PDGF.AB/ml final FS clot) demonstrated to be sufficient to attain a nearly complete closure of mesh interstices 14 days after grafting. TG-PDGF.AB incorporated in FS via a specific binding technology was shown to be effective in grafted third-degree burn wounds. The adhesive properties of the fibrin matrix in conjunction with the prolonged growth factor stimulus enabled by this binding technology could be favourable in many pathological situations associated with wound-healing disturbances. Copyright © 2013 John Wiley & Sons, Ltd.
从可生物降解生物基质中可控释放生长因子能够加速并改善受损伤口的愈合。本研究旨在确定从纤维蛋白生物基质中释放的具有转谷氨酰胺酶（TG）交联底物位点的血小板衍生生长因子AB（PDGF-AB）是否能改善严重热损伤的伤口愈合。在体外测定了TG-PDGF-AB的结合和释放动力学。对约克夏猪背部进行三度接触烧伤，烧伤后24小时行筋膜上坏死组织切除术。伤口部位覆盖自体网状（3:1）中厚皮自体移植物，并用吻合钉固定或用喷雾纤维蛋白密封剂（FS；每组n = 8）附着。TG-PDGF-AB利用凝血因子ⅩⅢa的TG活性与纤维蛋白生物基质结合，随后通过酶切释放。测试了FS中三种剂量的TG-PDGF-AB（100 ng、1 μg和11 μg/ml FS）。蛋白质印迹分析证明TG-PDGF-AB与纤维蛋白生物基质结合，随后通过酶切释放。与单独使用吻合钉相比，使用含有TG-PDGF-AB的喷雾FS可显著加速和改善伤口愈合。低浓度（100 ng-1 μg TG-PDGF-AB/ml最终FS凝块）已证明足以在移植后14天实现网状间隙几乎完全闭合。通过特定结合技术掺入FS中的TG-PDGF-AB在移植的三度烧伤伤口中显示出有效性。纤维蛋白基质的粘附特性与这种结合技术实现的延长生长因子刺激相结合，在许多与伤口愈合障碍相关的病理情况下可能是有利的。版权所有© 2013 John Wiley & Sons, Ltd.
