Cellular proliferation and cytokine responses of murine macrophage cell line J774A.1 to polymethylmethacrylate and cobalt-chrome alloy particles.

Wear debris from orthopedic joint implants have been postulated to initiate a cascade of complex cellular events that results in aseptic loosening of the prosthesis and eventually in loss of function of the device. The impact of biomaterials used in these devices on host inflammatory response has not been examined extensively. Polymethylmethacrylate (PMMA) and cobalt-chrome alloy (CoCr) are biomaterials widely used in orthopedic implant devices. Macrophages are an important component of the host inflammatory response, and we have examined the effect of PMMA and CoCr particles on the murine macrophage cell line J774A.1. Our objective was to obtain a comprehensive analysis of the particle-macrophage interaction, and we examined a number of basic biological responses of the J774A.1 cell line, including cell proliferation, apoptosis, cytokines secreted into the culture supernatant (TNFalpha, IL-1alpha, IL-6, and IL-12) and mRNA expression of the cytokines (TNFalpha, IL-1alpha, IL-6, IFN-alpha, M-CSF, and TGF-beta) in response to PMMA and CoCr particles. Our results indicate that the relative contribution of PMMA and CoCr particles in J774A.1 activation is negligible, and we observed a change in metabolic activity of J774A.1 cells only at higher concentrations of CoCr particles.

Biomaterials for tissue engineering: summary.

NASA: This article summarizes presentations and discussion at the workshop "Enabling Biomaterial Technology for Tissue Engineering," which was held during the Fifth World Biomaterials Congress in May 1996. Presentations covered the areas of material substrate architecture, barrier effects, and cellular response, including analysis of biomaterials challenges involved in producing specific tissue-engineered products.^ieng

Braided polypropylene augmentation device in reconstructive surgery of the anterior cruciate ligament: long-term clinical performance of 594 patients and short-term arthroscopic results, failure analysis by scanning electron microscopy, and synovial histomorphology.

Long-term clinical results and short-term arthroscopic and microscopic findings from two augmented reconstruction procedures for the ruptured anterior cruciate ligament are reported. The braided polypropylene ligament augmentation device (Kennedy model) was used with temporary double-end fixation in 279 patients to augment the attachment of the anterior cruciate ligament after acute proximal rupture and in 315 patients to augment a bone-tendon-bone autograft, mainly after chronic instability. Check arthroscopy was performed and the metal fixation hardware was removed after a mean of 11 months. Of the 569 patients evaluated, 101 partial or total breakages of the ligament augmentation device were found. Together with nine breakages detected late in the follow-up period, 110 (19.3%) failures were found. Most of these failures were accompanied by effusion that was immediately alleviated when the failed device was removed. No generalized synovitis was visible. Scanning electron microscopic analysis of 24 retrieved failed ligament augmentation devices showed fatigue to be the principal failure mode, together with local abrasion at the fracture. Synovial biopsies were taken during arthroscopy in 84 patients with and without ligament augmentation device-failure who had given informed consent, and histological evaluation revealed that in 21 patients, chronic but no acute synovial inflammation was found, and wear particles could be identified in foreign body cells in 17. Statistically, the presence of chronic synovitis was predicted neither by wear particles and foreign body cells nor by abrasion or fatigue failure of the ligament augmentation device. Irrespective of the failures, for which ligament augmentation device removal is recommended, in the final Orthopaedische Arbeitsgemeinschaft Knie evaluation (after a mean of 6.2 years), excellent and good clinical results were found in 83.6% of all 594 patients.

Interaction of macrophages with fibrous materials in vitro.

Fibrous materials have the potential of being used for tissue scaffolding. The interaction of macrophages with fibres of various compositions and sizes was observed in vitro. The following materials were tested: individual gold fibres; woven fibres of polyester and nylon; non-woven fibres of polybutylene/polypropylene 80:20 and polyester. All fibres had diameters between 2 and 40 microns. At the end of the 24 h incubation time, culture media were retrieved for the assay of tumour necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6), two cytokines secreted by activated macrophages. Fibre samples were processed for scanning electron microscopy (SEM), or for immunofluorescence labelling of the MAC-1 and ICAM-1 cell surface markers. Confocal microscopy was used for the latter, which was performed with the woven and non-woven samples. None of the fibre samples induced significant amounts of TNF-alpha or IL-6 secretion in the culture medium, suggesting that the cells did not activate this pathway. SEM on individual gold fibres showed that the fibre diameter had an effect on the morphology of the cells, namely on their extent of spreading. Larger fibres had a higher number of cells, which tended to cluster together without spreading extensively. When comparing woven and non-woven fibres, SEM showed that cells spread extensively on the woven fibres, whereas they tended to maintain their spherical shape on the non-woven fibres. Confocal microscopy demonstrated a difference between materials in the number of MAC-1 and ICAM-1 positive cells. These results demonstrate that a combination of morphological, immune and biochemical markers can be used to distinguish the response of elicited macrophages to various materials. The cells appeared to be only moderately activated on all materials tested, with changes in their morphology but without increased secretion of cytokines. The measured responses imply interactions between nominal fibre composition and fibre diameter.

Research directions in biomedical engineering.

The role of biomedical engineering and developments that affect it are outlined. Research areas that the authors believe will be of major importance at the beginning of the next century are discussed. They are: systems science and integrated biology; biomedical engineering in the cardiovascular system; biomaterials (metals, ceramics, and polymers); artificial organs; instrumentation and sensors; medical imaging (radiography, ultrasonic imaging, magnetic resonance imaging, and other techniques); biomedical computing; biomechanics; and rehabilitation. Some new areas for biomedical engineering research (molecular biology, minimally invasive surgery, home health care, and geriatric care) are examined.

Experimental mechanical and histologic evaluation of the Kennedy ligament augmentation device.

Reconstruction of the knee with a chronic injury to the anterior cruciate ligament is an unsolved problem. Biologic graft substitutes have failed to maintain knee stability in the longer postreconstruction intervals. In an attempt to overcome the limitations in graft performance, synthetic materials have been proposed to augment the biologic tissue. In this study, a 6-mm polypropylene braid Ligament Augmentation Device (LAD) possessing a tensile strength of 1500 N and excellent fatigue and creep properties was investigated as an adjunct to the MacIntosh/Marshall Over-the-Top repair. A two-year animal study of 54 adult goats was conducted in which experimental ACL defects were created and reconstructed with a transplant consisting of a portion of the rectus femoris tendon, prepatellar tissue, and the central one-third of the patellar tendon. The goats were equally divided between nonaugmented and LAD-augmented groups and sacrificed at three, six, 12, and 24 months after surgery. Mechanically, the augmented transplants were substantially stronger at the time of initial implantation (364N versus 26N) and again at two years (841N versus 528N). Intermediate times did not demonstrate a difference in strength. Histologically, the augmented transplants consisted of a loosely organized fibrous capsule surrounding the LAD. At 24 months, "insertion fibers" were noted to provide continuity between the fibrous tissue and bone on both the tibia and femur.

Effect of surface texture on the soft tissue response to polymer implants.

The ion beam etching process produces micro hairlike filaments on PTFE without causing any chemical or physiochemical alterations to the material. Implantation of this textured material subcutaneously, altered the interfacial cells and the kinetics of fibrous capsule development. Interfacial cells associated with textured interfaces (shown to be monocytic phagocytes) display increases in adhesion, vacuolization, filopodia formation, cytoplasmic-to-nuclear ratio, metabolism, acid phosphatase activity, and increased FBGC formation. The fibrous capsule associated with textured implants is reduced in thickness at 8 weeks but is similar to smooth controls at later time periods. The results of this investigation demonstrate that the surface texture of an implant is a critical variable in determining the soft tissue response to a material.

Biodegradation of a poly(alpha-amino acid) hydrogel. I. In vivo.

A new hydrogel material has been prepared by crosslinking a hydrophilic, nonionic poly(amino acid), poly(2-hydroxyethyl-L-glutamine). The material properties of the hydrogel can be controlled by variation in the crosslink density, and the swelling ratio was found to be a sensitive and convenient method for measuring the extent of in vivo biodegradation of implanted specimens. Degradation of the material was observed only during the first 2 weeks of subcutaneous implantation in rats, and is attributed to hydrolysis by proteolytic enzymes released during the acute and chronic stages of the normal inflammatory response.

Equine salmonellosis: a review.

Salmonellosis in Equidae occurs sporadically throughout the world; the incidence recorded ranges from less than 1 per cent to as much as 27 per cent. In 1976 there was a significant increase in disease and mortality caused by salmonellosis in horses in Britain and treatment was less successful than with other species. Data revealed a general progressive shift away from species specific salmonella serotypes towards the ubiquitous but less discerning strains of Salmonella typhimurium. The role of predisposing causes is assessed and treatment, prevention and zoonitic importance commented upon.

Effect of implant surface chemistry upon arterial thrombosis.

A series of poly(alpha-amino acid)s with controlled chemical variations were investigated in order to assess the effect of different chemical moieties upon arterial thrombosis. The gross implant surface properties ranged from hydrophobic to hydrophilic ionic and nonionic. The materials were tested by implantation within canine femoral and carotid arteries. Results were compared with the response to the polyurethane Biomer. The changes in implant surface chemistry elicited a range of response that varied from intense thrombosis and rapid vessel occlusion to minimal thrombosis and endothelialization. The results showed that no simple relationship exists between a gross surface property, such as hydrophobicity, and the degree of thrombosis resistance. Some hydrophobic and hydrophilic materials were found to have good thrombosis resistance, while others were found to have poor thrombosis resistance. Leukocytes were shown to play an important role in both initial thrombosis and endothelialization. The major difference between materials that progressed to rapid vessel occlusion and materials that remained patent was the degree of direct leukocyte adherence and spreading on the implant surface prior to extensive platelet aggregation (less than 30 min). It was consistent for both hydrophobic and hydrophilic materials that the lack of direct leukocyte adherence to the implant surface was associated with intense thrombosis and rapid vessel occlusion. Conversely, the presence of numerous leukocytes directly adherent to either hydrophobic or hydrophilic surfaces appeared to have a moderating effect upon thrombosis and vessels with these implants remained patent. In instances when thrombosis was nonocclusive, the surfaces of the thrombi became endothelialized, primarily through the transformation of mononuclear leukocytes into endothelial cells. This article includes a hypothetical model representing the sequence of events and alternative pathways occurring at the blood-material interface, with special attention given to the involvement of leukocytes in arterial thrombosis.

The presence of silicone in breast capsules.

The presence of silicon-containing compounds in the capsules of women undergoing secondary surgical procedures has been identified by energy dispersion X-ray analysis. The birefringence and surface configuration qualities have been examined by polarized light-microscopic and electron-microscopic methods. The data indicate that silicone polymer (polydimethyl siloxane) is present both within cells and in the intercellular matrix of the capsule; the source of this material is the silicone gel-filled implant. A histiocytic and foreign-body giant-cell response was found to be associated with the silicon-containing compounds. It remains conjectural whether this chronic response is associated with the pain present in significant breast capsule formation.

Effect of polyurethane morphology on blood coagulation.

A series of polyurethanes based on the hard segment MDI and soft segment PTMG were synthesized. The molecular weight of the PTMG was 730, 1000, and 2000, and ethylene diamine was used as chain extender. The fabrication process was varied so as to achieve the maximum disorder (nonequilibrium state) and maximum order, fully annealed. It was demostrated that the "quenched" non-equilibrium state reduces the rate of activation of the intrinsic systems, factor XII pathway, when compared to the fully annealed state. Platelet attachment is primarily affected by phase separation.