Despite advanced sterilization and aseptic techniques, infections associated with medical implants have not been eradicated. Most present coatings cannot simultaneously fulfil the requirements of antibacterial and antifungal activity as well as biocompatibility and reusability. Here, we report an antimicrobial hydrogel based on dimethyldecylammonium chitosan (with high quaternization)-graft-poly(ethylene glycol) methacrylate (DMDC-Q-g-EM) and poly(ethylene glycol) diacrylate, which has excellent antimicrobial efficacy against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and Fusarium solani. The proposed mechanism of the antimicrobial activity of the polycationic hydrogel is by attraction of sections of anionic microbial membrane into the internal nanopores of the hydrogel, like an 'anion sponge', leading to microbial membrane disruption and then microbe death. We have also demonstrated a thin uniform adherent coating of the hydrogel by simple ultraviolet immobilization. An animal study shows that DMDC-Q-g-EM hydrogel coating is biocompatible with rabbit conjunctiva and has no toxicity to the epithelial cells or the underlying stroma.

Scientific investigations involving collagen have inspired tissue engineering and design of biomaterials since collagen fibrils and their networks primarily regulate and define most tissues. The collagen networks form a highly organized, three-dimensional architecture to entrap other ingredients. Biomaterials are expected to function as cell scaffolds to replace native collagen-based extracellular matrix. The composition and properties of biomaterials used as scaffold for tissue engineering significantly affect the regeneration of neo-tissues and influence the conditions of collagen engineering. The complex scenario of collagen characteristics, types, fibril arrangement, and collagen structure-related functions (in a variety of connective tissues including bone, cartilage, tendon, skin and cornea) are addressed in this review. Discussion will focus on nanofibrillar assemblies and artificial synthetic peptides that mimic either the fibrillar structure or the elemental components of type I collagen as illustrated by their preliminary applications in tissue engineering. Conventional biomaterials used as scaffolds in engineering collagencontaining tissues are also discussed. The design of novel biomaterials and application of conventional biomaterials will facilitate development of additional novel tissue engineering bioproducts by refining the currently available techniques. The field of tissue engineering will ultimately be advanced by increasing control of collagen in native tissue and by continual manipulation of biomaterials. GENERAL DESCRIPTION ON COLLAGEN IN CONNECTIVE TISSUESThe extracellular matrix (ECM), provides physical support to tissues by occupying the intercellular space, acting not only as benign native scaffolding for arranging cells within connective tissues, but also as a dynamic, mobile, and flexible substance defining cellular behaviors and tissue function (1). For most soft and hard connective tissues (bone, cartilage, tendon, cornea, blood vessels, and skin) collagen fibrils and their networks function as ECM, the highly organized, three-dimensional (3D) architecture surrounding various cells. Collagen plays a dominant role in maintaining the biologic and structural integrity of ECM and is highly dynamic, undergoing constant remodeling for proper physiologic functions (1). Hence, the ideal goal of tissue regeneration is to restore both the structural integrity and the vivid remodeling process of native ECM, especially restoring the delicate collagen networks under which normal physiologic regeneration occurs.Collagen molecules have a triple-helical structure and the presence of 4-hydroxyproline resulting from a posttranslational modification of peptide-bound prolyl residues provides a distinctive marker of these molecules (2). To date, 28 collagen types have been identified; I, II, III, and V are the main types that make up the essential part of collagen in bone, cartilage, tendon, skin, and muscle. They also exist in fibrillar forms with elaborate 3D arrays in ECM (3-5).Bone tissu...

Background: Bone marrow-derived mesenchymal stem cells (BMSCs) are a widely researched adult stem cell population capable of differentiation into various lineages. Because many promising applications of tissue engineering require cell expansion following harvest and involve the treatment of diseases and conditions found in an aging population, the effect of donor age and ex vivo handling must be understood in order to develop clinical techniques and therapeutics based on these cells. Furthermore, there currently exists little understanding as to how these two factors may be influenced by one another.

Microtia is a congenital external ear malformation that can seriously influence the psychological and physiological well-being of affected children. The successful regeneration of human ear-shaped cartilage using a tissue engineering approach in a nude mouse represents a promising approach for auricular reconstruction. However, owing to technical issues in cell source, shape control, mechanical strength, biosafety, and long-term stability of the regenerated cartilage, human tissue engineered ear-shaped cartilage is yet to be applied clinically. Using expanded microtia chondrocytes, compound biodegradable scaffold, and in vitro culture technique, we engineered patient-specific ear-shaped cartilage in vitro. Moreover, the cartilage was used for auricle reconstruction of five microtia patients and achieved satisfactory aesthetical outcome with mature cartilage formation during 2.5 years follow-up in the first conducted case. Different surgical procedures were also employed to find the optimal approach for handling tissue engineered grafts. In conclusion, the results represent a significant breakthrough in clinical translation of tissue engineered human ear-shaped cartilage given the established in vitro engineering technique and suitable surgical procedure.This study was registered in Chinese Clinical Trial Registry (ChiCTR-ICN-14005469).

Multipotent mesenchymal stem cells (MSCs) in adult tissue are known to be less immunogenic and immunosuppressive. Previous study showed that primary cultures of human adipose-derived stem cells (ADSCs) shared their immunomodulatory properties with other MSCs. However, whether passaged human ADSCs can retain their immunomodulatory effect after in vitro expansion remains unknown. In addition, the mechanism of ADSC-mediated immunomodulatory effect remains to be elucidated. This study aimed to investigate these issues by using passaged human ADSCs as an in vitro study model. Flow cytometry showed that passaged ADSCs expressed human leukocyte antigen (HLA) class I but not class II molecules, which could be induced to express to a high level with interferon-gamma (IFN-gamma) treatment. The study found that passaged ADSCs could not elicit lymphocyte proliferation after co-culturing with them, even after IFN-gamma treatment. In addition, either IFN-gamma-treated or non-treated ADSCs could inhibit phytohemagglutinin (PHA)-stimulated lymphocyte proliferation. Moreover, passaged ADSCs could serve as the third-party cells to inhibited two-way mixed lymphocyte reaction (MLR). Further study using a transwell system also showed that this type of immunosuppressive effect was not cell-cell contact dependent. In defining possible soluble factors, we found that passaged ADSCs significantly increased their secretion of prostaglandin E2 (PGE2), but not transforming growth factor-beta (TGF-beta) and hepatocyte growth factor (HGF), when they were co-cultured with MLR. Furthermore, the result demonstrated that only PGE2 production inhibitor indomethacine, but not TGF-beta- and HGF-neutralizing antibodies, could significantly counteract ADSC-mediated suppression on allogeneic lymphocyte proliferation. These results indicated that in vitro expanded ADSCs retain low immunogenicity and immunosuppressive effect, and PGE2 might be the major soluble factor involved in the in vitro inhibition of allogeneic lymphocyte reaction.

Although several studies have shown that dermal fibroblasts possess adipogenic, osteogenic or chondrogenic differentiation potential, no study has characterized this cell population in detail, and there is as yet no evidence that a single dermal fibroblast can differentiate into all these types of cells. In this study, dermal fibroblasts were isolated from human foreskin using a regular dermal fibroblast culture system. These cells could be expended in adherent culture for over 40 cell doublings. In addition, dermal fibroblasts exhibited adipogenic, osteogenic and chondrogenic phenotypes when they were cultured in the presence of certain inducers. Importantly, clonal analysis showed that 6.4% (3/47) of the single-cell-derived clones were tripotent, 19.1% (9/47) of the clones were bipotent, and 10.6% (5/47) of the clones were unipotent. Furthermore, one of the three tested tripotent clones exhibited neurogenic and hepatogenic differentiation potential. Phenotypic analyses showed that the tripotent fibroblasts were nestin– vimentin+, which is different from the dermis-derived stem cells reported by others. These results indicate that dermal fibroblasts are a heterogeneous population containing progenitors with various levels of differentiation potential, and the nestin– vimentin+ fibroblasts may represent a novel type of multipotent adult stem cells in human dermis.

No abstract

No abstract