Polyurethane Implants Research Articles

Late Seroma Formation after Breast Surgery with Textured Silicone Implants: A Problem Worth Bearing in Mind

Sir: In mammary implantation surgery, when breast enlargement occurs, physicians should first exclude infection and then investigate the presence of friction irritation or a true allergic response.1 Late hematoma and seroma are rare complications with an unknown incidence; current theories on their cause are as yet unproven. Several authors have suggested that microtrauma of the textured surface on the capsule causes the formation of granular tissue with neovessels that with rupture may lead to hematoma formation.2–4 In fact, cases of late hematoma and seroma unrelated to macroscopic trauma have been strictly associated with textured or polyurethane implants.3,5 We report a series of eight late seromas (five subglandular and three submuscular) accounting for a 1.84 percent incidence in our series. Patients presented a progressive monolateral breast enlargement (Figs. 1 and 2), but just four reported that a trauma had occurred a few days before. Ultrasound-guided needle aspiration of the fluid permitted us to exclude infection after aspirate culture. All patients experienced seroma recurrence and underwent reoperation with prosthesis removal. Removed implants did not present macroscopic signs of rupture. Immediate implant replacement was performed only if a new submuscular pocket could be created after capsulectomy. Otherwise, the implant was reintroduced into the same submuscular pocket after a period of 6 months. No seroma recurrence was observed at 1-year follow-up.Fig. 1.: Clinical photograph of a patient who underwent bilateral subglandular breast augmentation and developed a right late seroma (frontal view).Fig. 2.: Echographic image showing the intracapsular late seroma.Textured-surface and polyurethane implants have been preferred because of their lower rates of capsular contraction than smooth-surface implants in the subglandular compartment. However, it is noteworthy that reports of late seromas started only after the introduction of textured implants; indeed, late seromas are not mentioned in earlier studies investigating complications associated with smooth implants. The majority of reports of late seromas are associated with textured implants. Moreover, all reports of late seromas and hematomas related to smooth implants are associated with additional factors believed to be the cause.3 Lastly, unbroken textured or polyurethane implants have been associated with late seromas and hematoma in the absence of any apparent causative factor.2–4 Thus, the assumption that textured breast implants may cause late seroma seems to be correct. The incidence of these complications may be higher than believed because most reports are presented as single cases and not as part of wider, long-term studies. On the basis of our findings and the data reported concerning the etiopathogenetic mechanisms of late hematomas and seromas, we probably should consider changing the type of the implant from textured to smooth whenever a prosthesis needs to be replaced after these complications occur. Indeed, the smooth implant eliminates the risk of the friction irritation caused by the textured implant. Although we did not replace in our patients any of the textured implants with smooth ones to preserve implant symmetry and, also, any recurrence, we would seriously consider the possibility of doing so should any other cases of late seroma come to our attention. The inclusion of these complications in the informed consent form may be worth considering. Long-term studies designed to investigate the underlying causes of late intracapsular seroma and hematoma are warranted to prevent these complications. Marco Mazzocchi, M.D., Ph.D. Department of Plastic and Reconstructive Surgery Perugia, Italy Luca A. Dessy, M.D., Ph.D. Bruno Carlesimo, M.D. Francesco Marchetti, M.D. Nicolò Scuderi, M.D. Department of Plastic and Reconstructive Surgery University “La Sapienza” Rome, Italy DISCLOSURE The authors have no financial interest to declare in relation to the content of this article.

Histological Features of Periprosthetic Mammary Capsules: Silicone vs. Polyurethane

Periprosthetic capsules are a common reaction of the body to silicone or polyurethane breast implants. The aim of this study was to evaluate similarities and differences in the histological features of periprosthetic capsules surrounding silicone implants and polyurethane foam-coated implants and to correlate those features with the age of the implants. Tissues were studied from 41 periprosthetic capsules surrounding textured prostheses and from 20 capsules surrounding polyurethane foam-coated implants. For each sample we evaluated synovial metaplasia, density of collagen fibers or fibrosis, orientation of collagen fibers, and foreign body reaction (granulomatous reaction). Synovial metaplasia was seen in the capsular tissue from both types of implant, but more so from capsules surrounding polyurethane implants more than 5 years old. The density and orientation of the collagen fibers and the foreign body reaction were very similar for the two types of implant.

Enlarging Breast Mass in a Patient with a History of Polyurethane Implants

Enlarging Breast Mass in a Patient with a History of Polyurethane Implants

Policy Forum: Putting People First: Services and Supports for People with Developmental Disabilities

### Objectives The implantable biomaterial devices are used for long term performance for the replacement of damaged or diseased tissues, especially for vascular grafts and artificial skin. Due to the rising number of patients with cardiovascular diseases (CVD) and the shortage of suitable autologous vessels, the demand for clinically effective synthetic small diameter vascular grafts is increasing. Improving biocompatibility of biomaterial is the goal of tissue engineering scientists attempt to minimise inflammatory responses into tolerance. Silk and Polyurethane (PU) are currently being trailed in the animal experiment as potential biomaterial used in different implantable medical device. Interleukin 1 beta (IL-1β) luciferase mouses are generated by incorporating the firefly luciferase gene driven by a 4.5-kb fragment of human IL-1β gene promoter (cHS4l-hIL-1β). In this study, IL-1β transgenic mice have been used to determine the IL-1β production after biomaterial implantation. The aim of this study is determine host responses to Silk or PU implants ± coating recombinant human tropoelastin (rhTE) in transgenic IL-1β mouse model. ### Methods The back of each IL-1β mouse (n = 18) was subcutaneously implanted with received 4 different treated implants, control Silk, rhTE-coated Silk, control PU and rhTE-coated PU implants. The in vivo luciferase signal of IL-1β expression in each mouse was imaged daily for 5 days post-surgery, and then 9mice were euthanised at 10 days (10D) and 3 weeks (3W) post-surgery. The implants were harvested and stained with H&E and Milligan's trichrome to assess inflammatory cell infiltration and collagen depositions. Performing immunohistochemistry stains, Von Willebrand factor (vWF) for neovascularisation, F480 for macrophage, Ly-6G and Ly-6C for neutrophil and proliferation maker Ki67 for proliferating cells. ### Results Significantly reduced the levels of IL-1β production was observed in rhTE-coated Silk implants compared to control Silk implants at 2 and 3days post-surgery. Comparing to control implants, less number of total inflammatory cells were found in rhTE-coated Silk (∼47% 3W) and rhTE-coated PU (∼54.64% 10D). Also a reduction of neovascularisation (∼43% 3w) and less proliferating inflammatory cells (∼58% 3W) were observed in rhTE-coated Silk. ### Conclusions Our results suggested that rhTE coating improves biocompatibility of Silk and PU, reducing inflammatory responses.

Differential effects of rolipram on chronic subcutaneous inflammatory angiogenesis and on peritoneal adhesion in mice

The specific PDE4 inhibitor (rolipram) has been shown to attenuate excessive accumulation/activation of inflammatory cells and fibroblasts and cytokine production in several pathological conditions through cyclic nucleotide modulation. Here, using the murine sponge model to induce chronic subcutaneous inflammatory response and to elicit the formation of intraperitoneal adhesions we explored the hypothesis that rolipram would exert beneficial effects on decreasing key components of both processes (inflammatory cell recruitment, angiogenesis, and deposition of extracellular matrix component). Two doses of rolipram (0.2 or 2 mg/kg/day) were administered orally for 7 days in groups of mice bearing either subcutaneous or intraperitoneal polyether–polyurethane implants. Rolipram was effective in inhibiting angiogenesis as assessed by hemoglobin content and VEGF levels in subcutaneous implants (about 40% with both doses) but failed to exert this activity in intraperitoneal implants. Conversely, accumulation of neutrophils and macrophages determined by measuring myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) activities intraimplant, respectively, was attenuated only in intraperitoneal implants by the treatment. Levels of TNF-α and MCP-1 were also determined and rolipram at both doses decreased the production of both cytokines in intraperitoneal implants. The levels of MCP-1 in the subcutaneous implants were not affected by the treatment. Fibrosis was evaluated by determining the amount of collagen and production of TGF-β1 intraimplant. Both parameters were attenuated by rolipram. These results have shown differential sensitivity of proliferating tissues to PDE4 inhibitor indicating that this agent may be used to target inflammatory angiogenesis selectively.

Beta‐adrenoceptor blockade delays granulation tissue formation in polyurethane sponge implants

The role of adrenoceptors in granulation tissue formation is not well understood. The aim of this study was to investigate the effects of alpha- and beta-adrenoceptor blockade on granulation tissue development using polyurethane (PU) implants in the rat. Animals were treated orally with propranolol (beta1- and beta2-antagonist), atenolol (beta1-antagonist) or phentolamine (alpha1- and alpha2-antagonist) until euthanasia. The control group received only water. All animals received subcutaneous implants of PU sponges. After 14 days, implants were collected, formalin-fixed and paraffin-embedded. Sections were stained with hematoxylin and eosin and Sirius red and immunostained for CD68 and alpha-smooth muscle actin. The number of inflammatory cells and the volume density of myofibroblasts and blood vessels were lower in the control group than in the propranolol- and atenolol-treated groups. The collagen fiber score was greater in the control group than in the propranolol- and atenolol-treated groups. The inflammatory infiltrate, collagen fiber score, blood vessel density or myofibroblast differentiation was not affected by phentolamine. The percentage of fibrovascular invasion was greater in the antagonist-treated groups than in the control group. Blockade of beta1- and beta2-adrenoceptors, but not alpha-adrenoceptors, impairs granulation tissue development in PU implants due to interference with the inflammatory response.

IFATS Collection: Adipose-Derived Stromal Cells Improve the Foreign Body Response

Many implanted devices fail due to the formation of an avascular capsule surrounding the device. Additionally, fat has long been known to promote healing and vascularization. The goals of this study were to identify potential mechanisms of the provascular actions of adipose-derived stromal cells (ASCs) and to improve implant biocompatibility. First, adult ASCs and fibroblasts from rats were attached to polyurethane and polystyrene in vitro and their cytokine secretion profile was analyzed. Secretion of vascular endothelial growth factor (VEGF) from ASCs was 10-70 times higher than fibroblasts after 3 and 6 days. Next, polyurethane, bare and with cellular coatings, was implanted subcutaneously in rats. The fibrous capsule surrounding bare polyurethane implants was 17%-32% thicker and the amount of collagen was 27% greater than the capsule surrounding ASC-coated implants. Finally, the microvessel density adjacent to ASC-coated polyurethane was approximately 50%-80% higher than bare polyurethane. In summary, ASCs attached to polyurethane have a dramatically increased VEGF production compared with fibroblasts in vitro, and these cells also produce an increased microvessel density in the surrounding tissue when implanted subcutaneously in rats. Disclosure of potential conflicts of interest is found at the end of this article.

Physical vapor deposition of zirconium or titanium thin films on flexible polyurethane highly support adhesion and physiology of human endothelial cells

The aim of this study was to develop and characterize novel metal-polymer constructs to improve the biocompatibility of flexible but hydrophobic polyurethane (PUR) implants. Using a physical vapor deposition (PVD) technique, thin films (< or =100 nm) of zirconium (Zr) or titanium (Ti) were deposited on the polyurethane surface. Both coatings displayed good stability when subjected to cross-cutting test and especially Zr showed only minor and superficial cracks in the scanning electron microscopy analysis. PVD coating resulted in significantly lowered contact angles and the standard surface free energy of wetting (Delta(wet)G degrees ) turned to more favorable negative values (Ti: -40; Zr: -30; untreated PUR (uPUR): +10.1 mN/m). This may lead to the highly enhanced adhesion and proliferation properties observed with human umbilical vein endothelial cells (HUVECs). In addition, the novel coatings had no toxic effect and even drastically reduced apoptosis rates of HUVECs. Cell morphology, nitric oxide production, and mitochondrial membrane potential--both at static and flow conditions--were superior compared with uPUR, thus demonstrating intact physiological functions. Therefore, we suggest that combining PUR as a flexible material with a thin coating of Zr or Ti as the improved biocompatible surface may have advantages for use, for example, vascular graft material.

LDI–glycerol polyurethane implants exhibit controlled release of DB-67 and anti-tumor activity in vitro against malignant gliomas

The purpose of the present study was to develop a biodegradable and biocompatible polyurethane drug delivery system based on lysine diisocyanate (LDI) and glycerol for the controlled release of 7- tert-butyldimethylsilyl-10-hydroxy-camptothecin (DB-67). DB-67 has yet to be implemented in any clinical therapies due to the inability to delivered it in sufficient quantities to impact tumor growth and disease progression. To remedy this, DB-67 was covalently incorporated into our delivery system by way of an organometallic urethane catalyst and was found to be dispersed evenly throughout the LDI–glycerol polyurethane discs. Scanning electron micrographs indicate that the LDI–glycerol discs are uniform and possess a pore distribution typical of the non-solvent casting technique used to prepare them. The release rates of DB-67 from the LDI–glycerol discs were found to vary with both time and temperature and were shown capable of delivering therapeutic concentrations of DB-67 in vitro. Cellular proliferation assays demonstrate that empty LDI–glycerol discs alone do not significantly alter the growth of malignant human glioma cell lines (U87, T98G, LN229 and SG388). DB-67-loaded LDI–glycerol polyurethane discs were found to inhibit cellular proliferation by 50% on average in all the malignant glioma cell lines tested. These results clearly demonstrate the long-term, slow release of DB-67 from LDI–glycerol polyurethane discs and their potential for postoperative intracranial chemotherapy of cancers.

In Vivo Biocompatibility of Sulfonated PEO‐grafted Polyurethanes for Polymer Heart Valve and Vascular Graft

Sulfonated poly(ethylene oxide) (PEO)-grafted polyurethane (PU) (PU-PEO-SO(3)) prepared by bulk modification was used to coat both PU heart valves and vascular grafts, and their in vivo biocompatibility was evaluated using a canine shunt method. The two devices were implanted for up to 39 days and retrieved at specific time points for the analysis of blood compatibility, biostability, and calcium deposition. When the surface of the retrieved specimens was examined using scanning electron microscopy, platelet adhesion and thrombus formation appeared to be significantly lesser formed on the PU-PEO-SO(3)-coated implants, compared with the untreated PUs. While molecular weights of untreated PUs were found by gel permeation chromatography to be decreased after 39 days from implantation, the same remained barely changed with the PU-PEO-SO(3)-coated ones. The inductively coupled plasma study indicated that the amount of deposited calcium was significantly reduced in the surface-modified PU implants. The efficacy of PU-PEO-SO(3)-coated implants in terms of blood compatibility, biostability, and calcification resistance may render them as a promising biomedical material in the application for blood/tissue-contacting tissues and organs.

Late Intracapsular Seroma in Subfascial Buttock Augmentation: A Case Report

Late intracapsular seroma and hematoma have been described frequently as a complication of breast augmentation surgery. However, there are few reports of late intracapsular seroma in buttock augmentation. Textured and polyurethane implants have been used for subfascial enlargement of the buttocks. In this article, the authors report a large late intracapsular bilateral seroma caused by a retrofascial polyurethane-covered implant used for buttock augmentation: 1,200 ml on one side and 300 ml on the other. This patient's intracapsular seroma was of sudden onset 2 years and 6 months after surgery, and apparently had no relation to any trauma, use of medication, or physical exercise. Local tissues, including the gluteal fascia, were distended such that the implant was replaced inside the muscle and there was no relapse of the seroma. Late intracapsular hematomas or seromas from implants for buttock and breast augmentation may have the same etiology, and textured implants seem to be involved. All the reports on the matter are associated with textured implants. Any late seroma or hematoma caused by a smooth implant is related to an additional factor that may be considered as the etiologic agent. Further studies aimed at a large-scale assessment of the cause and actual incidence of late seromas and hematomas from textured implants are required.

Osteointegração de osso bovino desvitalizado, hidroxiapatita de coral, poliuretana de mamona e enxerto autógeno em coelhos

OBJETIVO: Estudar comparativamente implantes de osso bovino desvitalizado, hidroxiapatita porosa de coral, poliuretana de mamona e enxerto ósseo autógeno no reparo de defeito ósseo de 6x10mm em fêmur de coelhos. MÉTODOS: Noventa e seis coelhos Nova Zelândia distribuídos em 4 grupos conforme o material de preenchimento do defeito ósseo. Após seguimento de 4 e 12 semanas, as peças foram submetidas a análise macroscópica, microscópica, radiográfica, tomográfica e histométrica. Aos resultados aplicou-se testes estatísticos de Kruskal-Wallis, Mann-Whitney, Fisher, “t” de Student e quiquadrado. RESULTADOS: O enxerto ósseo autógeno mostrou maior potencial osteogênico; o osso bovino desvitalizado produz maior reação inflamatória, maior número de cavidades císticas e lentidão de integração; a hidroxiapatita porosa de coral mantém a radiodensidade inicial; os implantes de osso bovino desvitalizado e poliuretana de mamona mostraram radiodensidades aumentadas conforme foram invadidos pelo tecido ósseo neoformado. CONCLUSÃO: O implante de osso bovino desvitalizado induz reparação tecidual guiada mais lenta quando comparado ao enxerto ósseo autógeno e aos implantes de hidroxiapatita porosa de coral e poliuretana de mamona.

Poliuretana de mamona (Ricinus communis) para desvio da crista tibial no cão

A luxação medial de patela é uma das principais afecções ortopédicas que afetam cães de raças de pequeno porte. Tendo como princípio que o desvio da crista tibial é uma das alterações anatômicas encontradas, este estudo objetivou avaliar o efeito da poliuretana de mamona (Ricinus communis) aplicada em defeitos produzidos experimentalmente na porção proximal medial da tíbia de cães normais em fase de crescimento. Para isto, foram utilizados 12 cães subdivididos aleatoriamente em 3 grupos de igual número, com mesmo tratamento, mas com análise histopatológica aos 30 (GI), 60 (GII) e 90 (GIII) dias. O estudo constou de avaliações clínica, radiográfica, macroscópica, histopatológica, tomográfica e análise estatística. Avaliação clínica demonstrou não haver rejeição do implante. A análise radiográfica revelou intensa reação periosteal e neoformações ósseas no local da implantação. Macroscopicamente observou-se espessamento da crista tibial, neoformações ósseas e desvio lateral da crista. Os achados à microscopia óptica revelaram presença de tecido conjuntivo fibroso ao redor da poliuretana, ausência de proliferação óssea em direção ao implante e proliferação de periósteo na face medial das tíbias. A tomografia computadorizada revelou desvio lateral da crista em 11 animais e estes desvios foram estatisticamente significantes em nível de 5% por meio do teste t pareado.

Localized gene delivery using antibody tethered adenovirus from polyurethane heart valve cusps and intra-aortic implants.

The present study investigated a novel approach for gene therapy of heart valve disease and vascular disorders. We formulated and characterized implantable polyurethane films that could also function as gene delivery systems through the surface attachment of replication defective adenoviruses using an anti-adenovirus antibody tethering mechanism. Our hypothesis was that we could achieve site-specific gene delivery to cells interacting with these polyurethane implants, and thereby demonstrate the potential for intravascular devices that could also function as gene delivery platforms for therapeutic vectors. Previous research by our group has demonstrated that polyurethane elastomers can be derivatized post-polymerization through a series of chemical reactions activating the hard segment amide groups with alkyl bromine residues, which can enable a wide variety of subsequent chemical modifications. Furthermore, prior research by our group investigating gene delivery intravascular stents has shown that collagen-coated balloon expandable stents can be configured with anti-adenovirus antibodies via thiol-based chemistry, and can then tether adenoviral vectors at doses that lead to high levels of localized arterial neointima expression, but with virtually no distal spread of vector. Thus, we sought to create two-device configurations for our investigations building on this previous research. (1) Polyurethane films coated with Type I collagen were thiol activated to permit covalent attachment of anti-adenovirus antibodies to enable gene delivery via vector tethering. (2) We also formulated polyurethane films with direct covalent attachment of anti-adenovirus antibodies to polyurethane hard segments derivatized with alkyl-thiol groups, thereby also enabling tethering of replication-defective adenoviruses. Both formulations demonstrated highly localized and efficient transduction in cell culture studies with rat arterial smooth muscle cells. In vivo experiments with collagen-coated polyurethane films investigated an abdominal aorta implant model in pigs using a button configuration that simulated the blood contacting environment of a vascular graft. One week explants of the collagen-coated polyurethane films demonstrated 14.3+/-2.5% of neointimal cells on the surface of the implant transduced with green fluorescent protein - adenovirus (AdGFP) vector loadings of 1 x 10(8) PFU. PCR studies demonstrated no detectable vector DNA in blood or distal organs. Similarly, polyurethane films with direct attachment of antivector antibodies to the surface were used in sheep pulmonary valve leaflet replacement studies, simulating the blood contacting environment of a prosthetic heart valve cusp. Polyurethane films with antibody tethered AdGFP vector (10(8) PFU) demonstrated 25.1+/-5.7% of attached cells transduced in these 1 week studies, with no detectable vector DNA in blood or distal organs. In vivo GFP expression was confirmed with immunohistochemistry. It is concluded that site-specific intravascular delivery of adenoviral vectors for gene therapy can be achieved with polyurethane implants utilizing the antivector antibody tethering mechanism.

The effect of microgeometry, implant thickness and polyurethane chemistry on the foreign body response to subcutaneous implants

We addressed the effect of implant thickness, implant porosity, and polyurethane (PU) chemistry on angiogenesis and on the foreign body response in rats. The following materials were implanted subcutaneously for 7 weeks then excised for histologic analysis: a solid PU; a solid polyurethane with silicone and polyethylene oxide (PU-S-PEO); porous expanded polytetrafluoroethylene (ePTFE); and porous polyvinyl alcohol sponge (PVA). Two thicknesses of PU-S-PEO were compared: 300 μm (thin) and 2000 μm (thick). Foreign body capsule (FBC) thickness was much less in PU-S-PEO implants than in PU implants. In addition, FBC were thinner in thin implants than in thick implants. FBC was much more dense in solid implants than in porous implants. As compared with solid implants, porous implants (PVA and ePTFE) led to a marked increase in the number of microvessels that developed adjacent to the implant, as observed both with hematoxylin/eosin staining and with an immunohistochemical anti-endothelial stain. We conclude that the polyethylene oxide and silicone moieties in PU reduce the thickness of the subsequent FBC. In addition, thin implants lead to a thin FBC. Porous implants (PVA and ePTFE) cause more angiogenesis than solid implants. These results may have implications for the measurement of blood-derived analytes by biosensors.

Bisphosphonate derivatized polyurethanes resist calcification

Calcification of polyurethane cardiovascular implants is an important disease process that has the potential to compromise the long-term function of devices such as polymer heart valves and ventricular assist systems. In this study we report the successful formulation and characterization of bisphosphonate-derivatized polyurethanes, hypothesized to resist implant calcification based on the pharmacologic activity of the immobilized bisphosphonate. Fully polymerized polyurethanes (a polyurea–polyurethane and a polycarbonate polyurethane) were modified (post-polymerization) with bromoalkylation of the hard segments followed by attachment of a bisphosphonate group at the bromine site. These bisphosphonate-polyurethanes resisted calcification in rat 60 day subdermal implants compared to nonmodified control polyurethane implants, that calcify. Bisphosphonates-modified polyurethanes were also studied in circulatory implants using a pulmonary valve cusp replacement model in sheep. Polyurethane cusps modified with bisphosphonate did not calcify in 90 day implants, compared to control polyurethane cusps implants, that demonstrated nodular surface oriented calcific deposits. It is concluded that bisphosphonate modified polyurethanes resist calcification both in subdermal implants and in the circulation. This novel biomaterial approach offers great promise for long-term blood stream implantation with calcification resistance.

Bioactive Polyurethane Implants with Hydroxyapatite

Bioactive Polyurethane Implants with Hydroxyapatite

Biomaterial-Induced Sarcoma: A Novel Model to Study Preneoplastic Change

In the study of carcinogenesis most interest has focused on carcinomas, as they represent the majority of human cancers. The recognition of the adenoma-carcinoma sequence both in humans and in animal experimental models has given the field of basic oncology the opportunity to elucidate individual mechanisms in the multistep development of carcinoma. The relative scarcity of human sarcomas coupled with the lack of adequate animal models has hampered understanding of the molecular genetic steps involved. We present an experimental model in the rat in which a high incidence of malignant mesenchymal tumors arise around a subcutaneously implanted biomaterial. Nine commercially available biomaterials were implanted in a total of 490 rats of the Fischer strain for 2 years. On average, macroscopic tumors were found in 25.8% of implantation sites over a period from 26 to 110 weeks after implantation. The most frequent tumors were malignant fibrous histiocytomas and pleomorphic sarcomas, although fibrosarcomas, leiomyosarcomas, and angiosarcomas readily developed, the latter especially around polyurethane implants. Of particular interest are the results of a detailed histological study of the capsules around the implanted biomaterials without tumors. Here a spectrum of change from focal proliferative lesions through preneoplastic proliferation to incipient sarcoma could be observed. A parallel immunohistochemical study of peri-implant capsules showed that proliferating cell nuclear antigen was of particular help in identifying these atypical proliferative lesions. To our knowledge this is the first description of a sarcoma model in which preneoplastic lesions can be readily identified and also reproducibly induced. This model provides the molecular biologist with defined stages in the development of mesenchymal malignancy, with which the multistage tumorigenesis hypothesis can be tested, analogous to the well-known adenoma-carcinoma sequence.

Meniscal repair by fibrocartilage in the dog: characterization of the repair tissue and the role of vascularity

Lesions in the avascular part of 20 canine menisci were repaired by implantation of a porous polyurethane. Seven menisci were not repaired and served as controls. The repair tissue was characterized by biochemical and immunological analysis. The role of vascularity in healing was studied by perfusion of menisci with Indian ink. Histologically, repair tissue inside the implants initially consisted of fibrous tissue containing type I collagen. After 2 months, fibrocartilaginous tissue developed inside the implants, whereas control defects only showed repair with fibrous tissue. Both type I and type II collagen, the two major collagen types of normal meniscal fibrocartilage, could be detected in this newly formed fibrocartilage. The implant guided vascular tissue from the periphery towards the lesion resulting in healing of the tear. After fibrocartilage had formed, vascularity decreased and was completely absent in mature fibrocartilage. Control defects remained filled with vascular connective tissue. Two-thirds of the longitudinal lesions were found to be healed partially or completely. It is concluded that implantation of a porous polymer does enhance vascularity sufficiently to result in healing of meniscal lesions extending into the avascular part. Healing takes place by repair tissue strongly resembling normal meniscal fibrocartilage.

Biodegradation of polyurethane foam, revisited, in the rat model.

In a prospective, randomized, controlled animal study, we systematically analyzed implanted polyurethane foam to determine the rate of degradation in the rat and to compare it to our previous human data. Sixteen 1-cm2 silicone-backed pieces of polyurethane foam were randomly implanted into dorsal subcutaneous pockets in each of 16 Sprague-Dawley rats. Eight animals had polyurethane implants removed at 3 and 6 months and the remaining 8 animals at 9 and 12 months. Specimens were examined either by histology or by scanning electron microscopy of recovered foam after collagenase digestion of the capsule. Histologically, there was evidence of foam degradation and a multinucleated giant cell inflammatory response surrounding the implants. With the scanning electron microscope, the strut width of the polyurethane foam upon implantation measured 51.4 +/- 1.3 microns (mean+SEM). This progressively decreased to 29.1 +/- 1.3 microns at 3 months, 16.6 +/- 0.6 micron at 6 months, 14.9 +/- 0.5 micron at 9 months, and 13.2 +/- 0.3 micron at 12 months (p < 0.0001). Duration of implantation has a significant impact on polyurethane degradation as measured by scanning electron microscopy in the rat animal model. The rate of degradation in the rat is much faster than in our human study, indicating that the rat studies cannot be used to draw conclusions regarding rate of biodegradation in humans.