生物材料作为治疗内植物相关性感染的药物载体的研究进展*

骨科内植物相关性感染是骨科的灾难性并发症，给社会及个人带来了极大的负担。近年来，新型生物材料得到了越来越多的关注，利用生物材料作为载体，负载相关药物，不仅在内植物相关性感染的治疗中取得了良好的效果，还可以促进骨组织的再生。本文对近年来用作药物载体的生物材料进行了综述。     

Interaction of dendritic cells with biomaterials

The interconnections between innate and adaptive immunity, with a focus on dendritic cells (DCs), in the context of combination products, are discussed. Biomaterials are shown to act as an adjuvant in the enhancement of the adaptive immune response to co-delivered antigen. Biomaterials are considered as agonists for DC maturation and several hypotheses as to the mechanism by which DCs recognize and respond to biomaterials are presented. There is the conceptualization of biomaterials with the idea of 'danger signals'. The goal is to design biomaterials to control DC phenotype and in this way control immune responses to combination products.     

Glial cell and fibroblast cytotoxicity study on plasma-deposited diamond-like carbon coatings

Diamond-like carbon films have been evaluated as coatings to improve biocompatibility of orthopedic and cardiovascular implants. This study initiates a series of investigations that will evaluate diamond-like carbon (DLC) as a coating for improved biocompatibility in chronic neuroprosthetic implants. Studies in this report assess the cytotoxicity and cell adhesion behavior of DLC coatings exposed to glial and fibroblast cell lines in vitro. It can be concluded from these studies that DLC coatings do not adversely affect 3T3 fibroblast and T98-G glial cell function in vitro. We also successfully rendered DLC coatings non-adhesive (no significant fibroblast or glial cell adhesion) with surface immobilized dextran using methods developed for other biomaterials and applications. Future work will further develop DLC coatings on prototype microelectrode devices for chronic neural implant applications.     

生物材料生物相容性的评价方法和发展趋势

背景：对生物材料进行生物相容性的评价是进入临床实验前的重点研究内容,但是目前国内外标准的评价体系尚未完全建立,影响了生物材料的研究。 目的：对生物材料生物相容性的评价方法进行回顾和展望。 方法：应用计算机检索2000-01/2010-08 PubMed数据库相关文章,检索词为“biomaterials,biocompatibility,evaluated methods,trend”,并限定文章语言种类为English。同时计算机检索2000-01/2010-08中国期刊网全文数据库(CNKI)相关文章,检索词为“生物材料,生物相容性,评价方法,研究进展”,并限定文章语言种类为中文。共检索到文献104篇,最终纳入符合标准的文献25篇。 结果与结论：生物材料必须具有良好的生物相容性才能确保临床应用的安全性。生物材料不引起明显的临床反应以及能耐受宿主各系统的作用而保持相对稳定、不被破坏和排斥的生物学性质则为生物相容性良好。生物相容性的评价是生物材料进入临床实验前必不可少的关键环节。随着分子生物学的迅速发展,生物材料生物相容性的评价方法研究手段逐渐多样化,其评价已从整体、细胞水平进入了分子水平。     

Biomaterials in Canada: the first four decades

Biomaterials research in Canada began in the 1960s. Over the past four decades significant contributions have been made across a broad spectrum covering dental, orthopaedic, cardiovascular, neuro, and ocular biomaterials. Canadians have also been active in the derivative area of tissue engineering. Biomaterials laboratories are now established in universities and research institutes from coast to coast, supported mainly by funding from the Federal and Provincial Governments. The Canadian Biomaterials Society was formed in 1971 and has played an important role in the development of the field. The Society played host to the 5th World Biomaterials Congress in Toronto in 1996. The work of Canadian researchers over the past four decades is summarized briefly. It is concluded that biomaterials and tissue engineering is a mature, strong area of research in Canada and appears set to continue as such into the future.     

生物材料研究经典论文、核心著者与期刊：SCI收录生物材料类期刊的引文分析

背景：第九次世界生物材料大会将于2012年在中国召开,中国生物材料科学研究已开始同国际接轨,其相关研究也成为热点,其发表的论文数量、作者人群和期刊品种非常之多,研究者很难从众多的文献中寻找资料。 目的：为使国内研究者了解国际相关研究轨迹和前沿,文章从引文分析的角度,选取SCI生物材料领域的10种期刊发文的引文进行分析,以获取该领域研究者所需的经典论文、核心著者和核心期刊,以期对相关研究者有帮助。 方法：应用计算机检索SCI(科学引文数据库)收录生物材料期刊,并根据其影响因子选取期刊,下载到所刊登文章引文    406 753条,并对数据利用Excl和Access进行统计分析。 结果与结论：经过统计分析获取Tissue engineering等10篇经典论文、Hench, Larry L.等10位核心作者和Biomaterials等20种核心期刊,生物材料相关科技者着重研究所列经典文章,掌握相关核心作者的研究动态,着重阅读上述核心期刊可以对相关研究有帮助。     

A new trichrome technique for PMMA embedded percutaneous implants for the study and characterization of epithelial integration

Abstract

Poly(methylmethacrylate) (PMMA) embedding is routinely used in histomorphometry to analyze the periprosthetic tissue response to the presence of an implant in situ. However, the embedment process can limit the variety of stains that can be successfully used to highlight different tissue types within the periprosthetic tissue. In this study, a new staining protocol, the modified trichrome method, was developed to simultaneously label the collagen fiber matrix, epithelial tissue morphology, vascular network, granulation tissue, and fibrous capsule that surround the percutaneous implant. The new staining technique was compared to established histological evaluation protocols, namely Masson’s trichrome and hematoxylin and eosin (H&E) protocols. The newly developed staining protocol for analyzing implant–soft tissue integration was significantly more effective in identifying cellular and tissue structures than previously established techniques. The detail found with the modified trichrome allows a high degree of structural quantification. The ultimate goal of the present research is to improve the long term soft tissue integration of implants made from different biomaterials. The modified trichrome can benefit translational studies through a more accurate quantification of both skin attachment mechanism and cellular response to the presence of percutaneous biomaterials.     

A vitreous carbon-polymethacrylate composite for dental implants.

A STUDY HAS BEEN CARRIED OUT ON THE STRUCTURE AND SURFACE TEXTure of a new dental implant material composed of vitreous carbon balloons (3 wt % or 6 wt %) and poly(methyl methacrylate). Tooth replica implants using this material had been successfully placed in baboons, and histologic study revealed normal alveolar bone and a peri-implant membrane with the connective tissue fibers oriented in a horizontal direction. Square wafers (10 mm X 10 mm X 1 mm) were studied, with the surface sandblasted in one-half of the specimens. Light microscopy revealed that in the 3% carbon specimens, the vitreous carbon micro-balloons were evenly spaced and often appeared to be fragmented within their spaces. S.E.M. studies revealed a finely porous surface with numerous large craters. Microballoons were often seen within the craters in the nonsandblasted specimens.     

The role of biomaterials in stem cell differentiation: applications in the musculoskeletal system

The capabilities of stem cells continue to be revealed, leading to excitement regarding potential new therapies. Regenerative medicine is an area in which stem cells hold great promise for overcoming the challenge of limited cell sources for tissue repair. Biomaterials play an important role in directing tissue growth and may provide another tool to manipulate and control stem cell behavior. Biomaterials are made from natural or synthetic polymers and can be processed into three-dimensional scaffolds designed to promote cell proliferation and/or differentiation that ultimately produces new tissue. Stem cells will have a significant impact on the fields of regenerative medicine and tissue engineering as a powerful cell source that will work, in conjunction with biomaterials, to treat tissue and organ loss. Herein, we survey our latest research on applying embryonic stem (ES) cells to hydrogel biomaterials for engineering musculoskeletal tissues, emphasizing the unique biomaterial requirements of ES cells for differentiation and tissue development.     

The effect of integrin-specific bioactive coatings on tissue healing and implant osseointegration

Implant osseointegration, defined as bone apposition and functional fixation, is a requisite for clinical success in orthopaedic and dental applications, many of which are restricted by implant loosening. Modification of implants to present bioactive motifs such as the RGD cell-adhesive sequence from fibronectin (FN) represents a promising approach in regenerative medicine. However, these biomimetic strategies have yielded only marginal enhancements in tissue healing in vivo. In this study, clinical-grade titanium implants were grafted with a non-fouling oligo(ethylene glycol)-substituted polymer coating functionalized with controlled densities of ligands of varying specificity for target integrin receptors. Biomaterials presenting the alpha5beta1-integrin-specific FN fragment FNIII 7-10 enhanced osteoblastic differentiation in bone marrow stromal cells compared to unmodified titanium and RGD-presenting surfaces. Importantly, FNIII 7-10-functionalized titanium significantly improved functional implant osseointegration compared to RGD-functionalized and unmodified titanium in vivo. This study demonstrates that bioactive coatings that promote integrin binding specificity regulate marrow-derived progenitor osteoblastic differentiation and enhance healing responses and functional integration of biomedical implants. This work identifies an innovative strategy for the rational design of biomaterials for regenerative medicine.     

Kinetics of colonization of a porous vitreous carbon percutaneous implant

Implants of porous vitreous carbon with pore diameters 200-500 microns were surgically placed in rabbits and pigs. Skin colonization experiments were carried out by topically inoculating concentrations of Staphylococcus aureus and Escherichia coli in a test area adjacent to the implant and to a remote control area. Subsequent swab cultures were taken at 6, 24, 48 and 72 h and one or more weeks. In vitro attachment studies were also performed using bacteria stained with FITC on 1 mm slices of the porous carbon. Proplast was used as a control. Results showed that despite a temporary high rate of colonization and obvious binding of the bacteria to the carbon, the skin-implant interface resists infection by both normal and pathogenic flora.     

Experimental model for observation of micromotion in cell culture

It is known that the micromotion between implant and bone inhibits direct bone growth either on or into implant surfaces in vivo. Nevertheless, biocompatibility tests in vitro of biomaterials for bone/implant interfaces are mainly performed under static conditions. This work describes a dynamic, in vitro experimental simulation of the effect of mutual, small-scale implant surface-tissue displacement on adhered cells. Disks of simulated tissue (PVP hydrogel) were subjected to cyclic micromotion ranging from 0 at the center to 1000 microm at the periphery at approximately 13 Hz, relative to biomaterial surfaces or tissue culture polystyrene controls populated with human osteoblasts in standard tissue culture plate wells. The effect of the interfacial micromotion on the number of cells remaining attached was quantitated by XTT assay. The activity level of the remaining cells was determined by an alkaline phosphatase assay, and cell stress was evaluated by nitrogen assay. Significantly more cells (ANOVA) became detached from similarly prepared surfaces of titanium, hydroxyapatite, and alumina compared to the polystyrene control, and detachment from alumina was greater than for the other two materials. The activity of the remaining attached cells was lower as compared to the static (no micromotion) control but not significantly different among the biomaterials. All nitrogen assays were negative, suggesting minimal cell stress occurred. The method is proposed as a useful and discriminating in vitro tool for biocompatibility studies focused on cell adhesion to biomaterials under conditions related to those which exist at the implant/bone interface in vivo, and it allows subsequent studies of the still-viable cells by other methods.     

The development of peptide-based interfacial biomaterials for generating biological functionality on the surface of bioinert materials

Biomaterials used in implants have traditionally been selected based on their mechanical properties, chemical stability, and biocompatibility. However, the durability and clinical efficacy of implantable biomedical devices remain limited in part due to the absence of appropriate biological interactions at the implant interface and the lack of integration into adjacent tissues. Herein, we describe a robust peptide-based coating technology capable of modifying the surface of existing biomaterials and medical devices through the non-covalent binding of modular biofunctional peptides. These peptides contain at least one material binding sequence and at least one biologically active sequence and thus are termed, "Interfacial Biomaterials" (IFBMs). IFBMs can simultaneously bind the biomaterial surface while endowing it with desired biological functionalities at the interface between the material and biological realms. We demonstrate the capabilities of model IFBMs to convert native polystyrene, a bioinert surface, into a bioactive surface that can support a range of cell activities. We further distinguish between simple cell attachment with insufficient integrin interactions, which in some cases can adversely impact downstream biology, versus biologically appropriate adhesion, cell spreading, and cell survival mediated by IFBMs. Moreover, we show that we can use the coating technology to create spatially resolved patterns of fluorophores and cells on substrates and that these patterns retain their borders in culture.     

Qualitative and quantitative observations of bone tissue reactions to anodised implants

Research projects focusing on biomaterials related factors; the bulk implant material, the macro-design of the implant and the microsurface roughness are routinely being conducted at our laboratories. In this study, we have investigated the bone tissue reactions to turned commercially pure (c.p.) titanium implants with various thicknesses of the oxide films after 6 weeks of insertion in rabbit bone. The control c.p. titanium implants had an oxide thickness of 17-200 nm while the test implants revealed an oxide thickness between 600 and 1000 nm. Routine histological investigations of the tissue reactions around the implants and enzyme histochemical detections of alkaline and acid phosphatase activities demonstrated similar findings around both the control and test implants. In general, the histomorphometrical parameters (bone to implant contact and newly formed bone) revealed significant quantitative differences between the control and test implants. The test implants demonstrated a greater bone response histomorphometrically than control implants and the osteoconductivity was more pronounced around the test implant surfaces. The parameters that differed between the implant surfaces, i.e. the oxide thickness, the pore size distribution, the porosity and the crystallinity of the surface oxides may represent factors that have an influence on the histomorphometrical results indicated by a stronger bone tissue response to the test implant surfaces, with an oxide thickness of more than 600 nm.     

Current trends in the enhancement of biomaterial osteointegration: biophysical stimulation

To enhance bone implant osteointegration, many strategies for improving biomaterial properties have been developed which include optimization of implant material, implant design, surface morphology and osteogenetic coatings. Other methods that have been attempted to enhance endogenous bone healing around biomaterials are different forms of biophysical stimulations such as pulsed electromagnetic fields (PEMFs) and low intensity pulsed ultrasounds (LIPUS), which were initially developed to accelerate fracture healing. To aid in the use of adjuvant biophysical therapies in the management of bone-implant osteointegration, the present authors reviewed experimental and clinical studies published in the literature over the last 20 years on the combined use of biomaterials and PEMFs or LIPUS, and summarized the methodology, and the possible mechanism of action and effectiveness of the different biophysical stimulations for the enhancement of bone healing processes around bone implanted biomaterials.     

2010 Panel on the biomaterials grand challenges

In 2009, the National Academy for Engineering issued the Grand Challenges for Engineering in the 21st Century comprised of 14 technical challenges that must be addressed to build a healthy, profitable, sustainable, and secure global community (http://www.engineeringchallenges.org). Although crucial, none of the NEA Grand Challenges adequately addressed the challenges that face the biomaterials community. In response to the NAE Grand Challenges, Monty Reichert of Duke University organized a panel entitled Grand Challenges in Biomaterials at the at the 2010 Society for Biomaterials Annual Meeting in Seattle. Six members of the National Academies-Buddy Ratner, James Anderson, Allan Hoffman, Art Coury, Cato Laurencin, and David Tirrell-were asked to propose a grand challenge to the audience that, if met, would significantly impact the future of biomaterials and medical devices. Successfully meeting these challenges will speed the 60-plus year transition from commodity, off-the-shelf biomaterials to bioengineered chemistries, and biomaterial devices that will significantly advance our ability to address patient needs and also to create new market opportunities.     

Assessment of stem cell/biomaterial combinations for stem cell-based tissue engineering

Biomaterials are used in tissue engineering with the aim to repair or reconstruct tissues and organs. Frequently, the identification and development of biomaterials is an iterative process with biomaterials being designed and then individually tested for their properties in combination with one specific cell type. However, recent efforts have been devoted to systematic, combinatorial and parallel approaches to identify biomaterials, suitable for specific applications. Embryonic and adult stem cells represent an ideal cell source for tissue engineering. Since stem cells can be readily isolated, expanded and transplanted, their application in cell-based therapies has become a major focus of research. Biomaterials can potentially influence e.g. stem cell proliferation and differentiation in both, positive or negative ways and biomaterial characteristics have been applied to repel or attract stem cells in a niche-like microenvironment. Our consortium has now established a grid-based platform to investigate stem cell/biomaterial interactions. So far, we have assessed 140 combinations of seven different stem cell types and 19 different polymers performing systematic screening assays to analyse parameters such as morphology, vitality, cytotoxicity, apoptosis, and proliferation. We thus can suggest and advise for and against special combinations for stem cell-based tissue engineering.     

The corrosion fatigue properties of surgical implants in a living body

Fatigue fracture of artificial implants in the human body, caused by the repeated application of stress, is well documented. It is known that the fatigue strength of implant materials decreases when they are exposed under in vivo corrosion conditions. There are, however, no investigations concerning the effect of body fluids on the fatigue characteristics of commonly used biomaterials. Accordingly, fatigue tests on machined stainless-steel AISI 316, and COP alloy rods have been conducted in the right lower leg of rabbit. These specimens were pierced through the hole drilled at the middle of the tibial bone. A cyclic tensile stress of frequency 5 or 10 Hz was applied to the rods. From the results, it was found that the fatigue strength at 5 x 10(6) cycles for AISI 316 under the in vivo environment was 680 MPa compared to 830 MPa in air and similarly for COP alloy, was 680 MPa in the living body compared to 800 MPa in air. These remarkable changes in fatigue strength associated with the in vivo environments are considered to be due to the corrosive action of body fluids on the biomaterials.