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Dual-functional biomimetic materials: nonfouling poly(carboxybetaine) with active functional groups for protein immobilization.

We introduce a dual-functional biocompatible material based on zwitterionic poly(carboxybetaine methacrylate) (polyCBMA), which not only highly resists protein adsorption/cell adhesion, but also has abundant functional groups convenient for the immobilization of biological ligands, such as proteins. The dual-functional properties are unique to carboxybetaine moieties and are not found in other nonfouling moieties such as ethylene glycol, phosphobetaine, and sulfobetaine. The unique properties are demonstrated in this work by grafting a polyCBMA polymer onto a surface or by preparing a polyCBMA-based hydrogel. PolyCBMA brushes with a thickness of 10-15 nm were grafted on a gold surface using the surface-initiated atom transfer radical polymerization method. Protein adsorption was analyzed using a surface plasmon resonance sensor. The surface grafted with polyCBMA very largely prevented the nonspecific adsorption of three test proteins, that is, fibrinogen, lysozyme, and human chorionic gonadotropin (hCG). The immobilization of anti-hCG on the surface resulted in the specific binding of hCG while maintaining a high resistance to nonspecific protein adsorption. Transparent polyCBMA-based hydrogel disks were decorated with immobilized fibronectin. Aortic endothelial cells did not bind to the polyCBMA controls, but appeared to adhere well and spread on the fibronectin-modified surface. With their dual functionality and biomimetic nature, polyCBMA-based materials are very promising for their applications in medical diagnostics, biomaterials/tissue engineering, and drug delivery.

Adsorption↗

Silicone based polyurethane materials: a promising biocompatible elastomeric formulation for cardiovascular applications.

The biocompatibility of a new material for cardiovascular applications constituted by a poly(ether)urethane (PEtU) and a silicone [polydimethylsiloxane (PDMS)] was evaluated. The achieved material shows properties similar to both polyurethanes and silicones. The material was transformed into porous membranes by a spray-deposition technique. Since any material preparation and manufacturing procedure may introduce some toxicity, in vitro cytotoxicity screening tests were carried out. Human umbilical vein endothelial cells (HUVECs) and a mouse fibroblasts cell line (L929) were cultivated with extracts obtained from materials containing 10, 40 and 100% (w/w) of PDMS. The commercially available Estane 5714-F1 and Cardiothane 51 were used as controls. Extracts were incubated up to 72 hours with HUVECs and L929 cells. The cytotoxic effect was evaluated by light microscopy, cell viability (MTT reduction and neutral red uptake) and proliferation (5-bromo-2'-deoxyuridine incorporation) tests. In vivo studies were carried out using materials containing the same PDMS percentages as for in vitro experiments. The same commercial controls were used. Results obtained with cell culture studies agreed with those obtained in the in vivo experiments and showed that the material preparation and manufacturing procedure do not introduce any toxicity in the products at each PDMS concentration investigated.

Animals↗

Coculture system to assess biocompatibility of candidate orthopaedic materials.

When examining the biocompatibility of materials for orthopaedic use, it is important to examine the in vitro response of osteoblasts and macrophages to the material. The purpose of the current study was to develop an in vitro system that more accurately models the dynamic macrophage and osteoblast interactive response to biomaterials. A filter coculture system was designed that enables two cell types to be separated, while permitting cellular mediators to diffuse through its porous membrane. Using the filter coculture system, macrophage and osteoblast interaction in response to polymethylmethacrylate particle exposure was examined. As a marker of bone resorption potential, the level of prostaglandin E2 released from the macrophage and osteoblast coculture was compared with traditionally used in vitro culture systems. Cells interacting in the filter coculture system were found to produce prostaglandin E2 levels significantly greater than those of traditional conditioned media transfer systems. This filter coculture system offers an in vitro model that accounts for the continual cell to cell mediator interaction of two cell types simultaneously exposed to an implant material. This system may be useful in examining the biocompatibility of candidate materials at the bone interface, and thus elucidating the mechanisms of material induced bone resorption.

Animals↗

[Visualizing living fibroblast on co-cultured denture base resin by green fluorescent protein marker introduced into the cell].

Visualizing living cells growing on co-cultured biomaterials is ideal for material biocompatibility evaluation in vitro. In this experiment, mouse fibroblasts L929 were labeled by introducing the gene coding enhanced green fluorescent protein (EGFP) marker into the cells. Morphology as well as proliferation of labeled cells surrounding or on the surface of co-cultured denture base resin slides were observed by use of phase-contrast microscope and fluorescent microscope directly. It was found that residual methyl methacrylate (MMA) in the denture base resin exhibited transient cytotoxicity to fibroblasts and this transient cytotoxicity could be eliminated by pre-extracting the resin with ddH2O for a short time. This fact demonstrated that even slight cytotoxicity of materials could be detected through imaging of living cells near material or material touched. And it was suggested that imaging of living cells co-cultured with biomaterial is helpful to understanding biocompatibility of materials more accurately.

Acrylic Resins↗

Ossicular chain reconstruction. Capitulum to malleus.

Ossicular chain reconstruction is most commonly performed for an absent or diseased incus. Reestablishing continuity by placing a strut prosthesis between the stapes capitulum and malleus handle minimizes the possibility of extrusion and displacement. Strut prostheses are made of hydroxyapetite, which is a highly biocompatible material that bonds to living bone.

Biocompatible Materials↗

Encrustation of biomaterials in the urinary tract.

The present review focuses on technological advances and relevant research related to encrustation of biomaterials in the urinary tract. The importance of physical and chemical biomaterial type, biocompatibility, material coatings such as hydrogels, and infection related to alloplastic materials used in urological practice are discussed. Recent in-vitro and in-vivo research has focused on materials that will reduce encrustation and bacterial biofilm formation, complications that limit the long-term use of urinary materials. Coordinating scientific resources in a multidisciplinary manner for a better understanding of factors that are involved in encrustation and biofilm formation will offer the potential to modify or resolve the problem of encrustation of foreign materials in the urinary tract.

Biocompatible Materials↗

Are total hip prostheses implanted with the use of methylmethacrylate biocompatible?

OBJECTIVES: The biocompatibility of total hip replacement prostheses and methylmethacrylate cement which is used for fixation of the prosthetic components has been subject to debate for three decades. METHODS: We have studied the host response to total hip replacement prostheses in a number of clinical and experimental investigations. RESULTS: Methylmethacrylate cement is immunologically relatively inert while it causes, in in vitro experiments and in vivo, a foreign body type of reaction. In cementless prostheses, the wear of polyethylene which is used for lining of the acetabular component causes a similar foreign body type of reaction. CONCLUSION: Ultimately, the total hip prosthesis cannot be made invisible to the host system. The host response can be controlled and reduced, but not eliminated by technical improvement and development of more biocompatible materials.

Biocompatible Materials↗

A new fluorocarbon for keratoprosthesis.

Previous studies have demonstrated the potential use of microporous, biocompatible materials to improve the long-term stability of keratoprosthesis. To determine the factors that will influence corneal tissue ingrowth into biocompatible, microporous materials, we have compared three types of fluorocarbon polymers--Impra, Gore-Tex, and Proplast--after intrastromal implantation in rabbit corneas. Despite similar physicochemical structures, a great difference was observed in histologic and ultrastructural cross sections after 4- and 8-month follow-ups. For Gore-Tex, we observed extrusion of the implant and infiltration of necrotic and inflammatory cells. All implants of Proplast also led to significant corneal damage resulting in extrusion of the material. Through the use of electron and light microscopy and image analysis, this study demonstrates the presence of cell differentiation and collagen synthesis in the pores of the Impra implant. Apart from biocompatibility, this experiment demonstrates the influence of pore size, porous microorganization, and biomechanical factors on prosthetic corneal material. Only Impra offers satisfactory interface, allowing fibroblastic cells and neocollagen synthesis into its pores, and it can become transparent.

Animals↗

Solubility of compositions in the system CaTi(x)Zr4-(x)(PO4)6 with x = 0-4.

In vitro solubility tests of granulated materials and coatings were carried out on some compositions in the system CaTi(x)Zr4-(x)(PO4)6 with x = 0-4, in order to find a biocompatible material which is less soluble than hydroxyapatite (HA) and can also be used as bone substitution material. The granulated materials were leached out by using circulating equipment in which the solvent flows in circulation. The coatings were tested under conditions where the sample containers undergo a circular movement. The results show better chemical stability of nearly all tested compounds compared with HA for both granulated materials and coatings.

Biocompatible Materials↗

Carbofilm-covered prostheses in plastic surgery: preliminary observations.

The optimal interface between an implant and the host organism is that which minimizes uncontrolled and irregular growth of fibrous tissue around the foreign material. One way to achieve this goal is to coat the outer surface of the implant with a biocompatible material. A thin film of turbostratic carbon (Carbofilm, Sorin Biomedica, Saluggia, Italy) can be applied as a thin coating on tissue expanders and breast implants made of silicone elastomers. The success of biologic trials with such implants in rats and cytologic studies with murine and human fibroblasts encouraged us to employ the Carbofilm technology in clinical situations. Preliminary results indicate that Carbofilm-coated implants satisfy the requirements of an ideal alloplastic material and induce a minimal periprosthetic inflammatory reaction, with the formation of a thin, soft, pliable, fibrous capsule around coated gel-filled silicone implants.

Animals↗

Early stages of human plasma proteins adsorption probed by Atomic Force Microscope.

Atomic Force Microscope (AFM) as a surface characterization technique has offered a great impulse in the advance of biocompatible materials. In this study AFM was implemented for the investigation of the early stages of adsorption of two human plasma proteins on titanium and hydrogenated carbon biocompatible thin films. The plasma proteins that were used were Human Serum Albumin and Fibrinogen, two of the most important proteins in human plasma. The concentration of the protein solutions was the same as that in human plasma. As the examined samples were soft, non-contact AFM mode was used to avoid their destruction. In order for the early stages of protein adsorption to be assessed, small incubation times were applied. AFM measurements in liquid buffer were also carried out, allowing the observation of the protein behaviour in an environment much closer to their native one. In addition, there was an assessment of the adsorption mechanism of the proteins on the above-mentioned biomaterials.

Adsorption↗

Corrosion evaluation of Ti-48Al-2Cr-2Nb (at.%) in Ringer's solution.

The corrosion behavior of Ti-48Al-2Cr-2Nb (at.%) in Ringer's solution was studied to evaluate its potential as a biocompatible material. Corrosion properties of Ti-6Al-4V were determined under the same conditions for comparison. Two electrochemical techniques, potentiodynamic anodic polarization and electrochemical impedance spectroscopy, were employed to test Ti-48Al-2Cr-2Nb and Ti-6Al-4V. Surface modifications to the samples were made by autoclaving and by oxidation in air at 500 degrees C and 800 degrees C. The results show excellent corrosion resistance for unmodified Ti-48Al-2Cr-2Nb, corroborated by the high values of polarization resistance and corrosion potential and low values of corrosion current and corrosion rate. Ti-48Al-2Cr-2Nb appears to possess corrosion characteristics similar to Ti-6Al-4V. Surface modification rendered the Ti-48Al-2Cr-2Nb material extremely corrosion resistant.

Alloys↗

In vitro biocompatibility assessment of naturally derived and synthetic biomaterials using normal human urothelial cells.

The reconstruction of urinary tissues often employs various types of biomaterials, and adequate material biocompatibility is essential for the successful reconstruction of urinary tissues. In this study we utilized a primary normal human urothelial cell culture system to evaluate the in vitro biocompatibility of a number of naturally derived biomaterials [i.e., bladder submucosa, small intestinal submucosa, collagen, and alginate] and polymeric biomaterials [i.e., poly(glycolic acid), poly(L-lactic acid), poly(lactic-co-glycolic acid), and silicone] that are either experimentally or clinically used in urinary reconstructive surgery. To determine the cytotoxic and bioactive effects of these biomaterials, the cell viability, metabolic activity, apoptotic properties, and DNA-synthesis activity were measured with four types of assays [Neutral Red, 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyl tetrazolium bromide, apoptotic activity, and tritiated thymidine incorporation assays] using extract and direct contact methods. Most of the biomaterials tested did not induce significant cytotoxic effects and exhibited normal metabolic function and cell growth in vitro. This normal primary human urothelial cell culture model is suitable for in vitro biocompatibility assessments and is able to provide information on the cell-biomaterial interactions and the ability of biomaterials to support bioactive cell functions.

Apoptosis↗

Immobilization of proteins on poly(methyl methacrylate) films.

Polymethyl methacrylate (PMMA) films were treated by oxygen plasma discharge followed by acrylic acid (AA) grafting. The amount of carboxyl groups introduced by the grafting of AA on to the film surfaces was in the range 0.47-9.48 mumol/cm2, depending on the pressure of the plasma chamber during the discharge treatment. The carboxyl groups of the PMMA film surface previously activated with water soluble carbodiimide were coupled with bovine serum albumin, collagen and gelatin. The protein immobilization on the surface was confirmed by attenuated total reflection Fourier transform infra-red spectroscopy (ATR-FTIR) and electron spectroscopy for chemical analysis (ESCA). The amount of albumin, collagen and gelatin immobilized on the PMMA surface was 6.25, 7.25 and 13.75 micrograms/cm2, respectively, as determined by the coomassie brilliant blue-protein interaction. The water contact angle of the PMMA film was markedly decreased by oxygen plasma treatment, AA grafting or protein immobilization, indicating the increase of hydrophilicity of the surface-modified PMMA films. The protein-immobilized PMMA films may be widely used as a biocompatible material.

Biocompatible Materials↗

Healing assessment of osseous defects of periapical lesions associated with failed endodontically treated teeth with use of freeze-dried bone allograft.

Freeze-dried bone allograft (FDBA) has been used extensively in periodontal surgery and in the treatment of pocket osseous defects resulting from inflammatory periodontal disease. No other endodontic investigation has used this type of graft material in the treatment of bony resorptive defects of the periapical lesions associated with failed endodontic therapy. Therefore this study was conducted with the use of FDBA, to assess healing ability of osseous defects after removal of periapical lesions associated with failed endodontically treated teeth. In all patients periapical lesions were surgically removed with retrograde amalgam seal and the graft material was then carefully packed without pressure into the bony defect. The lesions were fixed in 10% neutral buffered formalin and prepared for histologic examination. Long-term recall demonstrated bone regeneration and good tolerance of allograft material by the periapical tissues. The periapical lesions were either periapical granulomas or apical periodontal cysts. We conclude that FDBA is a biocompatible material of osteogenic potential and can be used effectively in treating osseous defects of periapical lesions associated with failed endodontically treated teeth.

Adolescent↗

In vitro biocompatibility assessment of poly(epsilon-caprolactone) films using L929 mouse fibroblasts.

Biodegradable and biocompatible materials are the basis for tissue engineering. As an initial step for developing vascular grafts, the in vitro biocompatibility of poly(epsilon-caprolactone) (PCL), recently suggested for several clinical applications, was evaluated in this study using L929 mouse fibroblasts. Different cellular aspects were analyzed in order to know the cell viability during cell culture on PCL films: adhesion, proliferation, morphology, LDH release and mitochondrial function. Since topography and other surface characteristics of materials play an essential part in cell adhesion, PCL membranes with either smooth or rough surface were prepared, characterized and used to carry out cell cultures. During short culture times, PCL produced a significant stimulation of mitochondrial activity evaluated by reduction of the MTT reagent. The results provide evidences of good adhesion, growth, viability, morphology and mitochondrial activity of cells on PCL films. Therefore, it can be concluded that PCL is a suitable and biocompatible material as a scaffold for vascular graft development.

Animals↗

Chalmers J. Lyons memorial lecture: Metal implants and the mandibular staple bone plate.

To briefly summarize our results, two of the five three-pin staples (40%) have survived and have functioned well for more than six years. Four of the five four-pin staples (80%) have survived five years or longer and are functioning well. Twenty-four of the 25 seven-pin staples (96%) are functioning well, some for a period of 4-1/2 years; a few in this group have been used a little less than a year. Our total percentage of survival with good function is 30 of 35, or 86%, which includes our pilot study of the three- and four-pin staples. A more significant statistic, however, might be those patients with staples who we feel have been free of any significant trouble; these are 27 of 35, or 77%. All of our patients have been subjected to peer review examination and grading by members of the oral surgery staff at Sinai Hospital. They were examined and graded according to three criteria. The first was clinical appearance which included firmness of the staple and clinical appearance of the gingiva (Fig 16). The second was radiographic evidence of bone loss along the transosteal pins and retentive pins (Fig 17). The third category was patient evaluation of improved function and stability of the lower denture (Fig 18). The peer review group used marks A, B, C, D, as excellent, good, fair, and failure. Four points were assigned to A, 3 points to B, 2 points to C, and 1 point to D, so that the grade averages for all three categories were as follows: clinical appearance, 3.6; radiographic appearance, 3.5; and patient evaluation, 3.9. The conclusion of the review group was that the mandibular staple was functioning well and that it was clinically useful. I have presented an overview of some of the characteristics of metallic implants that make them implantable devices, and some of the qualities of the host tissues that will allow placement of foreign material. We do not yet understand all of the factors that make alloplastic materials biocompatible or some of the reasons for rejection by the host. We need continued research in animal models to study new devices and new materials that might permit biologic attachments of the host to implant. We also need controlled clinical studies with peer review to establish reliability of those devices that are clinically useful. The mandibular staple has had an initial clinical trial that seems very promising and is worthy of continued clinical study and clinical application.

Atrophy↗