Amine-Rich Coatings to Potentially Promote Cell Adhesion, Proliferation and Differentiation, and Reduce Microbial Colonization: Strategies for Generation and Characterization

Biomaterial surface modification represents an important approach to obtain a better integration of the material in surrounding tissues. Different techniques are focused on improving cell support as well as avoiding efficiently the development of infections, such as by modifying the biomaterial surface with amine groups (–NH2). Previous studies showed that –NH2 groups could promote cell adhesion and proliferation. Moreover, these chemical functionalities may be used to facilitate the attachment of molecules such as proteins or to endow antimicrobial properties. This mini-review gives an overview of different techniques which have been used to obtain amine-rich coatings such as plasma methods and adsorption of biomolecules. In fact, different plasma treatment methods are commonly used with ammonia gas or by polymerization of precursors such as allylamine, as well as coatings of proteins (for example, collagen) or polymers containing –NH2 groups (for example, polyethyleneimine). Moreover, this mini-review will present the methods used to characterize such coatings and, in particular, quantify the –NH2 groups present on the surface by using dyes or chemical derivatization methods.

Identification of Novel FNIN2 and FNIN3 Fibronectin-Derived Peptides That Promote Cell Adhesion, Proliferation and Differentiation in Primary Cells and Stem Cells

In recent years, a major rise in the demand for biotherapeutic drugs has centered on enhancing the quality and efficacy of cell culture and developing new cell culture techniques. Here, we report fibronectin (FN) derived, novel peptides fibronectin-based intergrin binding peptide (FNIN)2 (18-mer) and FNIN3 (20-mer) which promote cell adhesion proliferation, and the differentiation of primary cells and stem cells. FNIN2 and 3 were designed based on the in silico interaction studies between FN and its receptors (integrin α5β1, αvβ3, and αIIbβ3). Analysis of the proliferation of seventeen-cell types showed that the effects of FNINs depend on their concentration and the existence of expressed integrins. Significant rhodamine-labeled FNIN2 fluorescence on the membranes of HeLa, HepG2, A498, and Du145 cells confirmed physical binding. Double coating with FNIN2 or 3 after polymerized dopamine (pDa) or polymerized tannic acid (pTA) precoating increased HBEpIC cell proliferation by 30–40 percent, suggesting FNINs potently affect primary cells. Furthermore, the proliferation of C2C12 myoblasts and human mesenchymal stem cells (MSCs) treated with FNINs was significantly increased in 2D/3D culture. FNINs also promoted MSC differentiation into osteoblasts. The results of this study offer a new approach to the production of core materials (e.g., cell culture medium components, scaffolds) for cell culture.

Surface Modification With Gelatin For Polyurethane Vascular Grafts: A Review

The means for developing synthetic vascular grafts to replace blood vessels is increasing extensively because of the limited supply of autologous vessels. Synthetic polymers as the alternatives still suffer from restenosis and thrombus formation. Natural polymers, on the other hand, are commonly biocompatible and biodegradable, compliment the synthetic ones. Blending, grafting and coating of natural polymers have been proposed to improve surface properties of synthetic polymers. Gelatin is a promising candidate to help improving synthetic vascular grafts surface owing to its ability to promote cell adhesion without promoting platelet aggregation at its surface. In this review, several techniques to incorporate gelatin onto synthetic polymers, mainly polyurethane, for vascular grafts application are summarized, together with the recent updates and potential development in the future.

TMIGD1 is Expressed at Low Levels in Abdominal Adhesion Tissue and Reduces Oxidative Stress in Peritoneal Mesothelial Cells

BackgroundPostoperative abdominal adhesion is one of the most commonly observed complications after abdominal surgery. However, there is no effective treatment for adhesion other than enterolysis. Mesothelial cell repair plays an extremely important role in the process of adhesion formation. Here, we hypothesize that transmembrane and immunoglobulin domain-containing 1 (TMIGD1) is expressed at low levels in abdominal adhesion tissue and can reduce oxidative stress and promote cell adhesion in peritoneal mesothelial cells.Materials and MethodsFirst, we performed gene microarray analysis and used qPCR, western blotting, immunohistochemistry and immunofluorescence to detect the expression of TMIGD1 in rat adhesion tissue and normal peritoneal tissue. Then, we established a TMIGD1-overexpressing HMrSV5 cell line and detected ROS, apoptosis, and the mitochondrial membrane potential by the MTT assay, western blotting, flow cytometry with 2’,7’-dichlorofluorescein diacetate (DCFH-DA) as a probe. Furthermore, we examined p38 phosphorylation in different TMIGD1-expressing cell lines and used a p38 inhibitor to determine whether the antioxidant effect of TMIGD1 is dependent on p38. Finally, we evaluated the adhesion ability of different TMIGD1 cell lines using scratch wound and adhesion assays.ResultsTMIGD1 was expressed at low levels in adhesion tissue and at lower levels in mesothelial cells. TMIGD1 overexpression alleviated H2O2-induced oxidative stress injury in human HMrSV5 cell lines. The phosphorylation level of p38 was higher in the TMIGD1-overexpressing cell line, and we found that the effect of TMIGD1 was inhibited by a p38 inhibitor. In addition, TMIGD1 overexpression inhibited mesothelial cell migration and promoted mesothelial cell adhesion.ConclusionTMIGD1 is expressed at low levels in abdominal adhesion tissue and can reduce H2O2-induced oxidative stress by promoting p38 phosphorylation. In addition, TMIGD1 can promote cell adhesion.# These authors contributed equally to this work.

Modified Methacrylate Hydrogels Improve Tissue Repair after Spinal Cord Injury

Methacrylate hydrogels have been extensively used as bridging scaffolds in experimental spinal cord injury (SCI) research. As synthetic materials, they can be modified, which leads to improved bridging of the lesion. Fibronectin, a glycoprotein of the extracellular matrix produced by reactive astrocytes after SCI, is known to promote cell adhesion. We implanted 3 methacrylate hydrogels: a scaffold based on hydroxypropylmethacrylamid (HPMA), 2-hydroxyethylmethacrylate (HEMA) and a HEMA hydrogel with an attached fibronectin (HEMA-Fn) in an experimental model of acute SCI in rats. The animals underwent functional evaluation once a week and the spinal cords were histologically assessed 3 months after hydrogel implantation. We found that both the HPMA and the HEMA-Fn hydrogel scaffolds lead to partial sensory improvement compared to control animals and animals treated with plain HEMA scaffold. The HPMA scaffold showed an increased connective tissue infiltration compared to plain HEMA hydrogels. There was a tendency towards connective tissue infiltration and higher blood vessel ingrowth in the HEMA-Fn scaffold. HPMA hydrogels showed a significantly increased axonal ingrowth compared to HEMA-Fn and plain HEMA; while there were some neurofilaments in the peripheral as well as the central region of the HEMA-Fn scaffold, no neurofilaments were found in plain HEMA hydrogels. In conclusion, HPMA hydrogel as well as the HEMA-Fn scaffold showed better bridging qualities compared to the plain HEMA hydrogel, which resulted in very limited partial sensory improvement.

Tailoring the Interface of Biomaterials to Design Effective Scaffolds

Tissue engineering (TE) is a multidisciplinary science, which including principles from material science, biology and medicine aims to develop biological substitutes to restore damaged tissues and organs. A major challenge in TE is the choice of suitable biomaterial to fabricate a scaffold that mimics native extracellular matrix guiding resident stem cells to regenerate the functional tissue. Ideally, the biomaterial should be tailored in order that the final scaffold would be (i) biodegradable to be gradually replaced by regenerating new tissue, (ii) mechanically similar to the tissue to regenerate, (iii) porous to allow cell growth as nutrient, oxygen and waste transport and (iv) bioactive to promote cell adhesion and differentiation. With this perspective, this review discusses the options and challenges facing biomaterial selection when a scaffold has to be designed. We highlight the possibilities in the final mold the materials should assume and the most effective techniques for its fabrication depending on the target tissue, including the alternatives to ameliorate its bioactivity. Furthermore, particular attention has been given to the influence that all these aspects have on resident cells considering the frontiers of materiobiology. In addition, a focus on chitosan as a versatile biomaterial for TE scaffold fabrication has been done, highlighting its latest advances in the literature on bone, skin, cartilage and cornea TE.