Current Methods Applied to Biomaterials - Characterization Approaches, Safety Assessment and Biological International Standards.

Safety and biocompatibility assessment of biomaterials are themes of constant concern as advanced materials enter the market as well as products manufactured by new techniques emerge. Within this context, this review provides an up-to-date approach on current methods for the characterization and safety assessment of biomaterials and biomedical devices from a physical-chemical to a biological perspective, including a description of the alternative methods in accordance with current and established international standards.

Synthesis, characterization and in vitro biocompatibility assessment of a novel tripeptide hydrogelator, as a promising scaffold for tissue engineering applications.

We have synthesized and characterized a self-assembling tripeptide hydrogelator Ac-l-Phe-l-Phe-l-Ala-NH2. A series of experiments showed that the hydrogel material could serve as a stabile and biocompatible physical support as it improves the survival of HEK293T cells in vitro, thus being a promising biomaterial for use in tissue engineering applications.

A comparative assessment by optical coherence tomography of the performance of the first and second generation of the everolimus-eluting bioresorbable vascular scaffolds.

AIMS: The first generation of the everolimus-eluting bioresorbable vascular scaffold (BVS 1.0) showed an angiographic late loss higher than the metallic everolimus-eluting stent Xience V due to scaffold shrinkage. The new generation (BVS 1.1) presents a different design and manufacturing process than the BVS 1.0. This study sought to evaluate the differences in late shrinkage, neointimal response, and bioresorption process between these two scaffold generations using optical coherence tomography (OCT). METHODS AND RESULTS: A total of 12 lesions treated with the BVS 1.0 and 12 selected lesions treated with the revised BVS 1.1 were imaged at baseline and 6-month follow-up with OCT. Late shrinkage and neointimal area (NIA) were derived from OCT area measurements. Neointimal thickness was measured in each strut. Strut appearance has been classified as previously described. Baseline clinical, angiographic, and OCT characteristics were mainly similar in the two groups. At 6 months, absolute and relative shrinkages were significantly larger for the BVS 1.0 than for the BVS 1.1 (0.98 vs. 0.07 mm² and 13.0 vs. 1.0%, respectively; P = 0.01). Neointimal area was significantly higher in the BVS 1.0 than in the BVS 1.1 (in-scaffold area obstruction of 23.6 vs. 12.3%; P < 0.01). Neointimal thickness was also larger in the BVS 1.0 than in the BVS 1.1 (166.0 vs. 76.4 µm; P < 0.01). Consequently, OCT, intravascular ultrasound, and angiographic luminal losses were higher with the BVS 1.0 than with the BVS 1.1. At 6 months, strut appearance was preserved in only 2.9% of the BVS 1.0 struts, but remained unchanged with the BVS 1.1 indicating different state of strut microstucture and/or their reflectivity. CONCLUSION: The BVS 1.1 has less late shrinkage and less neointimal growth at 6-month follow-up compared with the BVS 1.0. A difference in polymer degradation leading to changes in microstructure and reflectivity is the most plausible explanation for this finding.

Avaliação da dureza de diferentes metais utilizados na confecção de pinos pré-fabricados / Assessment of different metal hardness used in the manufacture of pre-fabricated posts

Diversos tipos de materiais metálicos vêm sendo pesquisados nos últimos anos, indicados para a confecção de pinos pré-fabricados, com o objetivo de serem utilizados como retentores intrarradiculares visando à restauração estética e funcional. Pode-se afirmar que, apesar de algum ganho na utilização de materiais não metálicos para a confecção de pinos intrarradiculares, o metal ainda representa uma alternativa altamente confiável, especialmente porque o desempenho clínico dos retentores metálicos tem se mostrado excelente. O presente estudo teve como finalidade avaliar a dureza Vickers de três diferentes metais (Titânio C. P., Liga de Titânio/Vanádio/Alumínio e Liga de Aço Inoxidável), que podem ser utilizados para este fim. Os resultados obtidos demonstraram significativas diferenças entre os três materiais testados.

The systematic production of cells for cell therapies.

Stem cells have emerged as the starting material of choice for bioprocesses to produce cells and tissues to treat degenerative, genetic, and immunological disease. Translating the biological properties and potential of stem cells into therapies will require overcoming significant cell-manufacturing and regulatory challenges. Bioprocess engineering fundamentals, including bioreactor design and process control, need to be combined with cellular systems biology principles to guide the development of next-generation technologies capable of producing cell-based products in a safe, robust, and cost-effective manner. The step-wise implementation of these bioengineering strategies will enhance cell therapy product quality and safety, expediting clinical development.

Medical devices in orthopedic applications.

Orthopedic medical devices have been extremely successful in restoring mobility, reducing pain, and improving the quality of life for millions of individuals each year. Their success is reflected in the worldwide biomaterials market, in which orthopedic devices dominated sales at approximately $14 billion in 2002. Of this, approximately $12 billion was spent on joint replacements. In spite of their overwhelming benefits and successes, orthopedic medical devices are not without risk of adverse effects. Most adverse joint replacement outcomes are thought to be mediated by degradation products generated by wear and electrochemical corrosion. Infection and flaws in device manufacturing are other noteworthy causes of orthopedic device failure. This article illustrates and discusses the uses, general properties, and limitations (including adverse outcomes) of orthopedic biomaterials, which are fundamental to understanding requirements for improving current orthopedic medical devices.

Current issues in the regulation of human tissue-engineering products in the European Union.

Tissue engineering (TE) is an emerging technology that combines expertise in life sciences, clinical medicine, and engineering. Current challenges in TE include anticipating and streamlining appropriate regulation with product development. Consequently this study has focused on views of developers, companies, and regulators on biological risks of TE products, aspects of commercial applications, and patentability. Most concerns about TE products focus on risk of cancer formation, infection risk, and rejection risk. Thus, at the present time, product developers should follow guidelines for medicinal products, in order to address product safety at an adequate level. According to the data of the present study, cell and biomaterial products, manipulated cells, and scaffolds appear to be the primary interest for commercial product development. In contrast, producing services were not considered as interesting. Constraints are also imposed by patentability, which stipulates demands for technical performance and highlights ethical issues, which are difficult to address.

[Retrieval and failure analysis of surgical implants in Brazil: the need for proper regulation]. / Análise de falhas de implantes cirúrgicos no Brasil: a necessidade de uma regulamentação adequada.

This paper summarizes several cases of metallurgical failure analysis of surgical implants conducted at the Laboratory of Failure Analysis, Instituto de Pesquisas Tecnológicas (IPT), in Brazil. Failures with two stainless steel femoral compression plates, one stainless steel femoral nail plate, one Ti-6Al-4V alloy maxillary reconstruction plate, and five Nitinol wires were investigated. The results showed that the implants were not in accordance with ISO standards and presented evidence of corrosion-assisted fracture. Furthermore, some of the implants presented manufacturing/processing defects which also contributed to their premature failure. Implantation of materials that are not biocompatible may cause several types of adverse effects in the human body and lead to premature implant failure. A review of prevailing health legislation is needed in Brazil, along with the adoption of regulatory mechanisms to assure the quality of surgical implants on the market, providing for compulsory procedures in the reporting and investigation of surgical implants which have failed in service.

Why compliance is not good enough.

Although reducing risks for medical devices is an element of product liability risk management, reducing risks for medical device manufacturers is the ultimate objective. With so much riding on the product development pipeline, what can manufacturers do to ensure a successful launch and healthy return on their investment? We argue in this editorial that the operating environment for the medical device industry is so dynamic that compliance is not enough. Instead, we suggest that risk abatement must become a part of a medical device manufacturer's operating strategy. We outline a robust risk abatement strategy involving corporate cultural changes, scenario modeling tools, and implementation systems.

Biocompatibility: the latest developments.

The standards for biological evaluation of medical devices are currently being evaluated. This article presents the rationale behind the current ISO 10993 series and discusses the work in progress to revise elements of the standards and to incorporate new areas. Particular issues being addressed include a new definition of biocompatibility, and quality of health, which will include product risk assessment and surveillance in the market place.

Can we develop a permanent pulsatile rotary blood pump? Yes, we can.

Active U.S. participation in the development of artificial heart technology began in 1966 with the award of six contracts. Since that beginning, and continuing to this day, we have been asking the same question, "Can we develop a system to take the place of the natural heart?" There are four formidable barriers that must be overcome before success can be achieved: technological development (Can the system perform as designed?); economic challenges (Can we finance the development?); regulatory hurdles (Can we get it approved for general use?); and acceptance (Will it be used, and will society accept it for what it is?). After 30 years, all but the last barrier has been overcome.

Structural integrity assessment of heart valve prostheses: a damage tolerance analysis of the CarboMedics Prosthetic Heart Valve.

The design of mechanical heart valve prostheses must satisfy three basic requirements: biocompatibility, efficiency and durability. Over the past 25 years of clinical use, pyrolytic carbon has proven to be biocompatible and thromboresistant, and is therefore the material of choice for mechanical heart valve prostheses. However, in recent years the material has been questioned in this application because it is brittle and susceptible to subcritical crack growth. This has raised concerns regarding the structural reliability of prostheses constructed from this material. This paper describes the application of the damage tolerance methodology to assess the structural integrity of heart valve prostheses made of pyrolytic carbon. In particular, an analysis of the CarboMedics Prosthetic Heart Valve (CPHV) is presented. A new measure of fatigue lifetime, the fatigue safe-life index, is introduced. Additionally, the degradation of structural integrity from cavitation erosion is examined. It is shown that structural integrity, especially for brittle materials, is not just a function of design, but involves the entire manufacturing process. The damage tolerance method can be applied to assess and ensure the structural integrity of pyrolytic carbon prosthetic heart valve components.

Wear assessment in bileaflet heart valves.

Sorin Biomedica has accumulated 20 years of experience in designing and manufacturing heart valves as well as in the development of turbostratic carbons, both as bulk coating (pyrolytic carbon, PyC) and as a thin film (Carbofilm). In designing a bileaflet valve, where hinges represent the most critical elements since wear occurs mainly at these points, we took into account: a) theoretical considerations on the geometry (flat-to-flat vs. curved-to-flat) of the coupling elements undergoing impact wear; b) kinematic coupling (sliding, rotation, rolling) between the moving parts in relation to friction wear; c) experimental wear rates of different material couples (PyC/PyC, metal/PyC) assessed by paying attention to test artifacts due to particle contamination; and d) wear mechanisms involving brittle fracture mechanics for bulk PyC and ductile fracture mode for metals. On the basis of the above evaluations a Carbofilm coated titanium alloy housing and PyC leaflets were developed for the Sorin Bicarbon valve. A flat-to-flat coupling between hinge stops and mating pivot surfaces for reducing the impact wear and a rolling action aimed at minimizing the friction wear were designed for the hinge. The Bicarbon long term durability has been assessed by accelerated wear tests conducted in comparison with clinically accepted bileaflet prostheses (CarboMedics and St. Jude Medical). The main results for the Bicarbon valve were, wear rates slightly lower or comparable to those found in the reference valves and wear morphology free from microfractures, while deep cracks associated with higher stress concentrations were detected on the PyC components of the reference valves. No mechanical failure or loss of functionality occurred up to 2,100 million cycles (equivalent of 52.5 years).

Assessment of the best compatible dialysis system: feasible application for bioelectrical impedance.

Since the introduction of hemodialysis procedure several attempts have been made to elucidate the material tissue interaction in order to evaluate the behaviour of immunosystem cellular and humoral responses to the material of patients on renal replacement therapy. Biochemical and sierological parameters have been considered as method for assessment of the best compatible dialysis. Nevertheless blood tests don't probably reflect the most important symptoms of clinical relevance. Thus we have applied bioelectrical impedance to assess the whole procedure/patient system. Resistance (R) changes during hemodialysis resulted strictly inversely correlated to the body weight variations during HD session (R < 0.96). Reactance (Xc) has also shown a progressive increase associated with an increment of phase angle, while Xc during clinical events such as hypotension, vomiting or cramps showed some transient falls. Also nutritional status and clinical well-being manifested a close relationship with bioelectrical parameters. It is therefore our feeling that BIA monitoring will provide a feasible tool to assess dialysis adequacy, of which biocompatibility represent a crucial aspect.

Artificial liver. Evolution and future perspectives.

Whole organ transplantation is the only clinically effective method of treating fulminant hepatic failure and chronic liver failure due to specific genetic, hepatocellular, and anatomic defects of liver function. However, wider application of liver transplantation is limited by shortage of organ donors, high cost, a relatively high morbidity rate, and need for life long immunotherapy. As a result, investigators have attempted to develop alternative methods to treat liver insufficiency. These ranged from use of plasma exchange to use of detoxification columns and extracorporeal devices loaded with various liver tissue preparations. Several liver support systems were developed in the 1950s and 1960s, but it was not until recently that advances in hepatocyte isolation and culture, improved understanding of hepatocyte-matrix interactions, availability of new biomaterials, improved hollow fiber technology, and better understanding of flow and mass transport across semipermeable membranes resulted in the development of a new generation of liver assist devices. Some of these devices are being tested in the clinical setting. In this article, the authors review past experience with liver support systems, critically examine the current status of the field by drawing primarily on their own experience, and attempt to speculate on the future direction of liver assist system development.

Economic implications of implant selection.

Numerous types of implantable biomaterials are available for a variety of applications. Although much has been written about the physical properties or biocompatibility issues, very few papers have focused on the economic feasibility of these materials. This article assesses financial factors associated with first metatarsophalangeal total joint prostheses.