http://www.mdpi.com/journal/ijms/special_issues/biocompatibility-materials/ Dear Colleagues, The theme of this special issue is Healing Materials that focuses on the design, characterization, and implementation of biomaterials for therapeutic applications. Currently, the vast majority of biomaterials employed in modern surgery are designed to passively reside in the tissue, with little to no design considerations for tissue interactions, such as common high performance metals (e.g. stainless steel, titanium alloy, cobalt chromium alloy) and polymers (e.g. polyethylene, silicone rubber, polyurethane). The limited exceptions to this general rule are surface-textured or hydroxyapatite coated materials to encourage tissue in-growth, and degradable polymers such as PLGA. This special issue places emphasis on next generation biomaterials that incorporate coating, molecular immobilization, drug release, matrix degradation or structural strategies that actively influence the healing state of the surrounding tissue. William Reichert Guest Editor Related Special Issues in other Journals Biocompatibility of Materials in Materials Submission All papers should be submitted to ijms@mdpi.com. To be published continuously until the deadline and papers will be listed together at the special issue website. Submitted papers should not have been published previously, nor be under consideration for publication elsewhere. All papers are refereed through a peer-review process. A guide for authors is available on the Instructions for Authors page. The International Journal of Molecular Sciences is an international peer-reviewed monthly journal published by MDPI. Open Access publication fees are 800 CHF per paper. English correction fees and/or formatting fees (250 CHF) will be added in certain cases (1050 CHF per paper for those papers that require extensive additional formatting and/or English corrections). http://www.mdpi.com/1422-0067/10/12/5411/ Microfabricated systems provide an excellent platform for the culture of cells, and are an extremely useful tool for the investigation of cellular responses to various stimuli. Advantages offered over traditional methods include cost-effectiveness, controllability, low volume, high resolution, and sensitivity. Both biocompatible and bioincompatible materials have been developed for use in these applications. Biocompatible materials such as PMMA or PLGA can be used directly for cell culture. However, for bioincompatible materials such as silicon or PDMS, additional steps need to be taken to render these materials more suitable for cell adhesion and maintenance. This review describes multiple surface modification strategies to improve the biocompatibility of MEMS materials. Basic concepts of cell-biomaterial interactions, such as protein adsorption and cell adhesion are covered. Finally, the applications of these MEMS materials in Tissue Engineering are presented. http://www.mdpi.com/1422-0067/10/12/5411/ Fri, 18 Dec 2009 00:00:00 CET International Journal of Molecular Sciences 2009-12-18 10 12 Review 5411 5441 1422-0067 Cell Culture on MEMS Platforms: A Review 2009-12-18 doi: 10.3390/ijms10125411 Ming Ni Wen Hao Tong Deepak Choudhury Nur Aida Abdul Rahim Ciprian Iliescu Hanry Yu http://www.mdpi.com/1422-0067/10/11/4963/ The aim of this study was to determine the optimal heat treatment conditions for enhancement of pressed silk-mediated 3D-like proliferation of normal human dermal fibroblasts, as well as to determine the responses to heat shock of cells and intracellular signaling pathways. The beginning of 3D-like pattern formation of cells was observed in the second week after the start of the experiment. The mean rates of beginning of 3D-like pattern formation by cells heat-treated at 40 ºC and 43 ºC for 10 min were significantly higher (3.2- and 8.6-fold, respectively) than that of untreated cells. We found that apoptosis had occurred in 7.5% and 50.0% of the cells at one week after heat treatment for 10 min at 43 ºC and 45 ºC, respectively. Western blot analysis demonstrated that phosphorylation of p38 MAPK and that of Hsp27 were markedly increased by heat treatment at 43 ºC for 10 min. The results of an experiment using a p38 MAPK inhibitor and Hsp27 inhibitor suggest that activation of p38 MAPK by heat shock is associated with 3D-like cell proliferation and that Hsp27 contributes to the inhibition of apoptosis. The results of this study should be useful for further studies aimed at elucidation of the physiologic mechanisms underlying thermotherapy. http://www.mdpi.com/1422-0067/10/11/4963/ Thu, 12 Nov 2009 00:00:00 CET International Journal of Molecular Sciences 2009-11-12 10 11 Article 4963 4976 1422-0067 Heat Shock-Induced Three-Dimensional-Like Proliferation of Normal Human Fibroblasts Mediated by Pressed Silk 2009-11-12 doi: 10.3390/ijms10114963 Fukumi Hiragami Hirotoshi Motoda Toshiaki Takezawa Chiyuki Takabayashi Shigeki Inoue Yuji Wakatake Yoshio Kano http://www.mdpi.com/1422-0067/10/10/4375/ The in vivo healing process of vascular grafts involves the interaction of many contributing factors. The ability of vascular grafts to provide an environment which allows successful accomplishment of this process is extremely difficult. Poor endothelisation, inflammation, infection, occlusion, thrombosis, hyperplasia and pseudoaneurysms are common issues with synthetic grafts in vivo. Advanced materials composed of decellularised extracellular matrices (ECM) have been shown to promote the healing process via modulation of the host immune response, resistance to bacterial infections, allowing re-innervation and reestablishing homeostasis in the healing region. The physiological balance within the newly developed vascular tissue is maintained via the recreation of correct biorheology and mechanotransduction factors including host immune response, infection control, homing and the attraction of progenitor cells and infiltration by host tissue. Here, we review the progress in this tissue engineering approach, the enhancement potential of ECM materials and future prospects to reach the clinical environment. http://www.mdpi.com/1422-0067/10/10/4375/ Mon, 12 Oct 2009 00:00:00 CEST International Journal of Molecular Sciences 2009-10-12 10 10 Review 4375 4417 1422-0067 ECM-Based Materials in Cardiovascular Applications: Inherent Healing Potential and Augmentation of Native Regenerative Processes 2009-10-12 doi: 10.3390/ijms10104375 Anna V. Piterina Aidan J. Cloonan Claire L. Meaney Laura M. Davis Anthony Callanan Michael T. Walsh Tim M. McGloughlin http://www.mdpi.com/1422-0067/10/10/4352/ High-density polyethylene (PE) foils were modified by an Ar+ plasma discharge and subsequent grafting with biomolecules, namely glycine (Gly), polyethylene glycol (PEG), bovine serum albumin (BSA), colloidal carbon particles (C) or BSA and C (BSA + C). As revealed by atomic force microscopy (AFM), goniometry and Rutherford Backscattering Spectroscopy (RBS), the surface chemical structure and surface morphology of PE changed dramatically after plasma treatment. The contact angle decreased for the samples treated by plasma, mainly in relation to the formation of oxygen structures during plasma irradiation. A further decrease in the contact angle was obvious after glycine and PEG grafting. The increase in oxygen concentration after glycine and PEG grafting proved that the two molecules were chemically linked to the plasma-activated surface. Plasma treatment led to ablation of the PE surface layer, thus the surface morphology was changed and the surface roughness was increased. The materials were then seeded with vascular smooth muscle cells (VSMC) derived from rat aorta and incubated in a DMEM medium with fetal bovine serum. Generally, the cells adhered and grew better on modified rather than on unmodified PE samples. Immunofluorescence showed that focal adhesion plaques containing talin, vinculin and paxillin were most apparent in cells on PE grafted with PEG or BSA + C, and the fibres containing α-actin, β-actin or SM1 and SM2 myosins were thicker, more numerous and more brightly stained in the cells on all modified PE samples than on pristine PE. An enzyme-linked immunosorbent assay (ELISA) revealed increased concentrations of focal adhesion proteins talin and vinculin and also a cytoskeletal protein β-actin in cells on PE modified with BSA + C. A contractile protein α-actin was increased in cells on PE grafted with PEG or Gly. These results showed that PE activated with plasma and subsequently grafted with bioactive molecules and colloidal C particles, especially with PEG and BSA + C, promotes the adhesion, proliferation and phenotypic maturation of VSMC. http://www.mdpi.com/1422-0067/10/10/4352/ Mon, 12 Oct 2009 00:00:00 CEST International Journal of Molecular Sciences 2009-10-12 10 10 Article 4352 4374 1422-0067 Improved Adhesion, Growth and Maturation of Vascular Smooth Muscle Cells on Polyethylene Grafted with Bioactive Molecules and Carbon Particles 2009-10-12 doi: 10.3390/ijms10104352 Martin Parizek Nikola Kasalkova Lucie Bacakova Petr Slepicka Vera Lisa Martina Blazkova Vaclav Svorcik http://www.mdpi.com/1422-0067/10/9/3861/ Resin-based dental restorative materials are extensively used today in dentistry. However, significant concerns still remain regarding their biocompatibility. For this reason, significant scientific effort has been focused on the determination of the molecular toxicology of substances released by these biomaterials, using several tools for risk assessment, including exposure assessment, hazard identification and dose-response analysis. These studies have shown that substances released by these materials can cause significant cytotoxic and genotoxic effects, leading to irreversible disturbance of basic cellular functions. The aim of this article is to review current knowledge related to dental composites’ molecular toxicology and to give implications for possible improvements concerning their biocompatibility. http://www.mdpi.com/1422-0067/10/9/3861/ Fri, 04 Sep 2009 00:00:00 CEST International Journal of Molecular Sciences 2009-09-04 10 9 Review 3861 3899 1422-0067 Molecular Toxicology of Substances Released from Resin–Based Dental Restorative Materials 2009-09-04 doi: 10.3390/ijms10093861 Athina Bakopoulou Triantafillos Papadopoulos Pavlos Garefis http://www.mdpi.com/1422-0067/10/8/3442/ Biocompatible materials are of considerable interest in the development of cell/drug delivery carriers for therapeutic applications. This paper investigates the effects of the Bloom index of gelatin on its interaction with retinal pigment epithelial (RPE) cells. Following two days of culture of ARPE-19 cells with gelatin samples G75-100, G175, and G300, the in vitro biocompatibility was determined by cell proliferation and viability assays, and glutamate uptake measurements, as well as cytokine expression analyses. The mitochondrial dehydrogenase activity in the G300 groups was significantly lower than that of G75-100 and G175 groups. The Live/Dead assays also showed that the gelatin samples G300 induced mild cytotoxicity. In comparison with the treatment of gelatins with low Bloom index, the exposure to high Bloom strength gelatins markedly reduced the glutamate uptake capacity of ARPE-19 cells. One possible explanation for these observations is that the presence of gelatin samples G300 with high viscosity in the medium may affect the nutrient availability to cultured cells. The analyses of pro-inflammatory cytokine IL-6 expression at both mRNA and protein levels showed that the gelatins with low Bloom index caused less cellular inflammatory reaction and had more acceptable biocompatibility than their high Bloom strength counterparts. These findings suggest that the Bloom index gives influence on cellular responses to gelatin materials. http://www.mdpi.com/1422-0067/10/8/3442/ Mon, 03 Aug 2009 00:00:00 CEST International Journal of Molecular Sciences 2009-08-03 10 8 Article 3442 3456 1422-0067 The Role of Bloom Index of Gelatin on the Interaction with Retinal Pigment Epithelial Cells 2009-08-03 doi: 10.3390/ijms10083442 Jui Yang Lai http://www.mdpi.com/1422-0067/10/7/3224/ Synthetic polymers belonging to the aliphatic polyester group have become highly promising biomaterials for reconstructive medicine. The purpose of the present work is a biological evaluation of lactide-glycolide co-polymer (PLGA) and its composites with carbon fibers (PLGA+CF) or hydroxyapatite (PLGA+HA). The cytotoxicity of the evaluated materials towards hFOB 1.19 human osteoblast-like cells was assessed. Moreover, during the one-year contact of the assessed materials with living osseous tissue, the progress of bone formation was analyzed and the accompanying process of the materials’ degradation was evaluated. The materials under evaluation proved to be biocompatible. http://www.mdpi.com/1422-0067/10/7/3224/ Wed, 15 Jul 2009 00:00:00 CEST International Journal of Molecular Sciences 2009-07-15 10 7 Article 3224 3234 1422-0067 The Evaluation of the Possibilities of Using PLGA Co-Polymer and Its Composites with Carbon Fibers or Hydroxyapatite in the Bone Tissue Regeneration Process – in Vitro and in Vivo Examinations 2009-07-15 doi: 10.3390/ijms10073224 Magdalena Cieślik Anna Mertas Anna Morawska-Chochół Daniel Sabat Rajmund Orlicki Aleksander Owczarek Wojciech Król Tadeusz Cieślik http://www.mdpi.com/1422-0067/10/7/2972/ Tissue engineering is a multidisciplinary field focused on in vitro reconstruction of mammalian tissues. In order to allow a similar three-dimensional organization of in vitro cultured cells, biocompatible scaffolds are needed. This need has provided immense momentum for research on “smart scaffolds” for use in cell culture. One of the most promising materials for tissue engineering and regenerative medicine is a hyaluronan derivative: a benzyl ester of hyaluronan (HYAFF®). HYAFF® can be processed to obtain several types of devices such as tubes, membranes, non-woven fabrics, gauzes, and sponges. All these scaffolds are highly biocompatible. In the human body they do not elicit any adverse reactions and are resorbed by the host tissues. Human hepatocytes, dermal fibroblasts and keratinocytes, chondrocytes, Schwann cells, bone marrow derived mesenchymal stem cells and adipose tissue derived mesenchymal stem cells have been successfully cultured in these meshes. The same scaffolds, in tube meshes, has been applied for vascular tissue engineering that has emerged as a promising technology for the design of an ideal, responsive, living conduit with properties similar to that of native tissue. http://www.mdpi.com/1422-0067/10/7/2972/ Fri, 03 Jul 2009 00:00:00 CEST International Journal of Molecular Sciences 2009-07-03 10 7 Review 2972 2985 1422-0067 Hyaluronan Benzyl Ester as a Scaffold for Tissue Engineering 2009-07-03 doi: 10.3390/ijms10072972 Vincenzo Vindigni Roberta Cortivo Laura Iacobellis Giovanni Abatangelo Barbara Zavan http://www.mdpi.com/1422-0067/10/3/1300/ One of the ultimate goals of wound healing research is to find effective healing techniques that utilize the regeneration of similar tissues. This involves the modification of various wound dressing biomaterials for proper wound management. The biopolymer chitosan (b-1,4-D-glucosamine) has natural biocompatibility and biodegradability that render it suitable for wound management. By definition, a biocompatible biomaterial does not have toxic or injurious effects on biological systems. Chemical and physical modifications of chitosan influence its biocompatibility and biodegradability to an uncertain degree. Hence, the modified biomedical-grade of chitosan derivatives should be pre-examined in vitro in order to produce high-quality, biocompatible dressings. In vitro toxicity examinations are more favorable than those performed in vivo, as the results are more reproducible and predictive. In this paper, basic in vitro tools were used to evaluate cellular and molecular responses with regard to the biocompatibility of biomedical-grade chitosan. Three paramount experimental parameters of biocompatibility in vitro namely cytocompatibility, genotoxicity and skin pro-inflammatory cytokine expression, were generally reviewed for biomedical-grade chitosan as wound dressing. http://www.mdpi.com/1422-0067/10/3/1300/ Wed, 18 Mar 2009 00:00:00 CET International Journal of Molecular Sciences 2009-03-18 10 3 Review 1300 1313 1422-0067 In Vitro Models in BiocompatibilityAssessment for Biomedical-Grade Chitosan Derivatives in Wound Management 2009-03-18 doi: 10.3390/ijms10031300 Lim Chin Keong Ahmad Sukari Halim