Sivasubramanian Srinivasan, Chandrasekar Gayathri, Svensson Akusjärvi Sara, Thangam Ramar, Sathuvan Malairaj, Kumar R B S, Hussein Hawraa, Vincent Savariar, Madhan Balaraman, Gunasekaran Palani, Kitambi Satish S
Department of Virology, King Institute of Preventive Medicine and ResearchChennai, India.
Department of Microbiology, Tumor and Cell Biology, Karolinska InstitutetSolna, Sweden.
Front Pharmacol. 2017 Jul 18;8:433. doi: 10.3389/fphar.2017.00433. eCollection 2017.
The potential of multifunctional wound heal biomaterial relies on the optimal content of therapeutic constituents as well as the desirable physical, chemical, and biological properties to accelerate the healing process. Formulating biomaterials such as amnion or collagen based scaffolds with natural products offer an affordable strategy to develop dressing material with high efficiency in healing wounds. Using image based phenotyping and quantification, we screened natural product derived bioactive compounds for modulators of types I and III collagen production from human foreskin derived fibroblast cells. The identified hit was then formulated with amnion to develop a biomaterial, and its biophysical properties, and effects were characterized. In addition, we performed functional profiling analyses by PCR array to understand the effect of individual components of these materials on various genes such as inflammatory mediators including chemokines and cytokines, growth factors, fibroblast stimulating markers for collagen secretion, matrix metalloproteinases, etc., associated with wound healing. FACS based cell cycle analyses were carried out to evaluate the potential of biomaterials for induction of proliferation of fibroblasts. Western blot analyses was done to examine the effect of biomaterial on collagen synthesis by cells and compared to cells grown in the presence of growth factors. This work demonstrated an uncomplicated way of identifying components that synergistically promote healing. Besides, we demonstrated that modulating local wound environment using biomaterials with bioactive compounds could enhance healing. This study finds that the developed biomaterials offer immense scope for healing wounds by means of their skin regenerative features such as anti-inflammatory, fibroblast stimulation for collagen secretion as well as inhibition of enzymes and markers impeding the healing, hydrodynamic properties complemented with other features including non-toxicity, biocompatibility, and safety.
多功能伤口愈合生物材料的潜力取决于治疗成分的最佳含量以及理想的物理、化学和生物学特性，以加速愈合过程。用天然产物配制诸如羊膜或胶原蛋白基支架等生物材料，为开发高效伤口愈合敷料材料提供了一种经济实惠的策略。通过基于图像的表型分析和定量，我们从人包皮成纤维细胞中筛选天然产物衍生的生物活性化合物，以寻找I型和III型胶原蛋白产生的调节剂。然后将鉴定出的活性成分与羊膜配制，开发出一种生物材料，并对其生物物理性质和效果进行了表征。此外，我们通过PCR阵列进行功能谱分析，以了解这些材料的各个成分对与伤口愈合相关的各种基因的影响，这些基因包括趋化因子和细胞因子等炎症介质、生长因子、刺激胶原蛋白分泌的成纤维细胞标志物、基质金属蛋白酶等。进行基于流式细胞术的细胞周期分析，以评估生物材料诱导成纤维细胞增殖的潜力。进行蛋白质免疫印迹分析，以检查生物材料对细胞胶原蛋白合成的影响，并与在生长因子存在下生长的细胞进行比较。这项工作展示了一种简单的方法来识别协同促进愈合的成分。此外，我们证明使用含有生物活性化合物的生物材料调节局部伤口环境可以促进愈合。本研究发现，所开发的生物材料通过其皮肤再生特性，如抗炎、刺激成纤维细胞分泌胶原蛋白以及抑制阻碍愈合的酶和标志物，以及与其他特性（包括无毒性、生物相容性和安全性）互补的流体动力学特性，在伤口愈合方面具有巨大的应用前景。
