Hydrogel Implants Research Articles

Ergebnisse der SaluCartilage-Implantation bei viertgradigen Knorpelschäden im Bereich des Kniegelenks

This prospective report presents SaluCartilage hydrogel implants, an alternative therapy option in the treatment of chondral defects. For the prospective study between October 2002 and July 2003, 18 patients suffering from stage IV chondral defects received 49 hydrogel implants and were subsequently examined by means of clinical, radiological, and magnetic resonance imaging assessment. The knee function was classified using the McDermott score. The average McDermott score was improved to 75 points (p<0.05) after 3 months postoperatively and to 80 points (p<0.05) 6 months postoperatively, but after 12 months it decreased to 69 points. After 3 and 6 months, the MRI showed in all patients that there was fluid around the hydrogel implants without dislocation. After 12 months postoperatively the hydrogel implants had been destroyed in two patients. The short-term results showed subjective and objective improvement of the medical conditions probably because of the placeholder function. This alternative should be critically discussed because of the inadequate connection to the bone with risk of dislocation.

Analysis of 30 Breast Implant Rupture Cases

The detection and evaluation of implant ruptures have been an issue for many years. If a ruptured implant is not removed, noncohesive silicone gel may spread to surrounding tissue, causing granuloma, redness of the affected skin, firmness of the breast tissue and skin, or distant migration [2]. When a ruptured or leaking saline type prosthesis is not removed or replaced with a new one, severe deformity of the breast may result. Once this occurs, I have found that many cases present difficulty in the reconstruction of the deformity to breasts with a symmetric appearance. The authors state that when they encountered rupture of a hydrogel breast implant, the gel had adhered to surrounding tissue, accompanied by inflammation and granuloma formation. Also, they state that the surgical procedure required removal of the granuloma and extensive debridement of the affected skin. Diagnostic methods used to detect implant rupture include a squeeze test, mammography, sonography, computed tomographic scan, and magnetic resonance imaging (MRI). Among these, MRI is reported to be the most reliable method for detecting rupture of the implant [1], which the authors article supports. Sonography is a valuable adjunct in the evaluation of only anterior breast parenchymal pathology. Furthermore, the sensitivity and specificity of sonography may vary depending on the experience of the attending radiologist. Mammography itself may cause implant rupture [3]. Also, patients with severe capsular contracture are unable to receive mammography. Recently, a patient in Japan noticed her breast implant rupture during the course of mammography. She subsequently sued the doctor, which raised the issue of how breast cancer should be checked among those with implants. In my opinion, mammography should not be used for patients with breast implants unless either a rupture or breast cancer are strongly suspected, as evidenced by other types of evaluations. At this point, however, MRI seems to be the most reliable imaging method for evaluating patients with breast implants. No diagnostic technique offers 100% accuracy in finding an early rupture or leak of saline, noncohesive silicone, or hydrogel breast implants. Probably the best way to check these conditions is to use a battery of techniques, which means checking local symptoms such as pain, mass, swelling, redness, and firmness; noting a change in the shape and size of the breasts; and administering the squeeze test, sonography, and MRI. Among these diagnostic procedures, the authors demonstrated that the linguine sign of the MRI is the most reliable for detecting signs of rupture or leaking of the implant. Because hydrogel implants are not so popular throughout the world, it is important to know what happens if ruptured implants are not removed after many years. The authors reviewed only one case of this type in their report. Further study is required to detect early signs of rupture or leaking hydrogel implants. With regard to the silicone type prosthesis, cohesive silicone implants currently are available in many countries. These cohesive silicone implants may rupture or leak. Furthermore, the degree of silicone cohesivity varies depending on product types or companies. More studies are required to determine whether the ruptured or leaking cohesive silicone breast implantmust be removed or replacedwith a new one. If this type of condition requires treatment, the question arises as to the best way of finding the leak or rupture of the cohesive silicone prosthesis. Because cohesive silicone implants are relatively new products becoming popular in the world, it is necessary to learn more information about this type of implant. As professional doctors, once we use breast implants for our patients, we are obligated to ensure that they are always happy with their breasts. Correspondence to: Email: info@mega-clinic.com Aesth. Plast. Surg. 29:470 471, 2005 DOI: 10.1007/s00266-005-0061-9

Modified Fibrin Hydrogels stimulate Angiogenesisin vivo: potential Application to increase Perfusion of Ischemic Tissues

The lack of angiogenesis in ischemic tissues is a major health problem and many studies aim to explore strategies to locally increase blood perfusion. Our approach is to use covalently modified fibrin-based hydrogels as a matrix that induces endothelial cell survival in vitro and angiogenesis in vivo. Fibrin hydrogels were covalently modified by L1Ig6, a specific receptor for cell survival integrin avb3 that is expressed on angiogenic endothelial cells. In addn., L1Ig6-modified matrixes were filled with growth factors VEGF-A165 or bFGF. These hydrogels were applied on growing shell-free chicken chorioallantoic membranes (CAMs) and the developing vasculature was found to be increased by .apprx.50 %. Moreover, the increase in av-integrin levels in the CAMs underlying the hydrogel implants were investigated and found to be increased by .apprx.40 % and .apprx.100 %, resp., after CAM stimulation with L1Ig6 alone or in combination with growth factors VEGF-A165 and bFGF. Therefore, modified fibrin hydrogels provide an interesting way to design an implant that can be introduced at the site of ischemia, and provides a scaffold and release system for growth factors that induce specific tissue responses. [on SciFinder (R)]

Dual growth factor-induced angiogenesis in vivo using hyaluronan hydrogel implants

Crosslinked hyaluronan (HA) hydrogels preloaded with two cytokine growth factors, vascular endothelial growth factor (VEGF) and keratinocyte growth factor (KGF), were employed to elicit new microvessel growth in vivo. As a major glycosaminoglycan (GAG) component of extracellular matrix (ECM), HA is an excellent biopolymeric building block for new biomimetic, biocompatible therapeutic materials. HA hydrogel film samples were surgically implanted in the ear pinnae of mice, and the ears were harvested at 7 or 14 days post-implantation. Histologic analysis showed that each of the groups receiving an implant demonstrated significantly more microvessel density than control ears undergoing surgery but receiving no implant ( p < 0.001 ). Treatment groups receiving either co-delivery of both KGF and VEGF, an HA hydrogel lacking a growth factor or HA hydrogels containing a single cytokine were statistically unchanged with time, whereas treatment with KGF alone produced continuing increases in vascularization from day 7 to day 14. Strikingly, presentation of both VEGF and KGF in crosslinked HA generated intact microvessel beds with well-defined borders. In addition, an additive response to co-delivery of both cytokines in the HA hydrogel was observed. The HA hydrogels containing KGF+VEGF produced the greatest angiogenic response of any treatment group tested ( NI = 5.4 at day 14, where NI is a neovascularization index). This was 33% greater vessel density than in the next largest treatment group, that received HA+KGF ( NI = 4.0 , p < 0.002 ). New therapeutic approaches for numerous pathologies could be notably enhanced by the localized, sustained angiogenic response produced by release of both VEGF and KGF from crosslinked HA films.

The repair of brain lesion by implantation of hyaluronic acid hydrogels modified with laminin

The hyaluronic acid (HA) hydrogels modified with laminin were used for implantation in rat brain in present study, in order to investigate its effects in reparation of injury in the CNS. Cross-linked HA hydrogels were synthesized and their characteristics were analyzed. Laminin, an extracellular matrix protein, which participates in neuronal development and survival, was immobilized on the backbone of the hydrogels. Hydrogels unmodified and modified with laminin were implanted into cortical defects mechanically created in rats and their ability to improve tissue reconstruction was then evaluated. After 6 and 12 weeks of implantation, sections of brains were processed with Nissl and Glees staining for revealing neural cell bodies and fibers, with DAB histochemistry for detecting the blood vessels, as well as with immunocytochemistry for recognizing GFAP. The sections were also taken to SEM and TEM for ultrastructral examination. The results showed that the HA hydrogels synthesized had mechanical properties and rheological behavior similar to the brain tissue. After being implanted into the lesion of the cortex, the porous hydrogels created a scaffold, which could support cell infiltration and angiogenesis, and simultaneously inhibit the formation of glial scar. In addition, HA hydrogels modified with laminin could promote neurite extension. It seems possible that the tissue engineering technique may pave the way to repair injury in the CNS as suggested by the results in present study.

Promoted Growth of Murine Hair Follicles by Controlled Release of Growth Factors from Biodegradable Hydrogel

This study is an investigation to evaluate how the controlled release of different growth factors affects the hair follicle growth of mice in the second anagen stage of hair cycle. For the controlled release of basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF), they were incorporating into biodegradable gelatin hydrogels, while a biodegradable collagen hydrogel was used for incorporation of vascular endothelial growth factor (VEGF). After subcutaneous implantation of the different hydrogels incorporating each growth factor or injection of phosphate buffered saline (PBS) containing the same dose of growth factor into the back of mice, the hair follicle growth was evaluated photometrically and histologically based on four parameters: the skin color of reverse side of the implanted or injected site, the number of vessels newly formed, the area occupied by hair follicle tissue, and the hair length. The area in close proximity to the implanted site of hydrogels incorporating growth factor was still dark in color 10 days after application. The hydrogel incorporating any type of growth factor enabled the hair follicles to increase the size, leading significantly enhanced area occupied by hair follicles per unit area of tissue. Implantation of the hydrogels incorporating growth factor increased significantly the number of blood vessels newly formed. Moreover, the length of hair shaft was elongated by the hydrogel incorporating growth factor to a significantly higher extent than the corresponding growth factor. Neither empty gelatin nor collagen hydrogels affected the hair follicle growth. These results indicate that the hydrogel incorporating growth factor induced the anagen-preservable activity. We conclude that the controlled release enabled growth factors to positively act on the hair growth cycle of mice, irrespective of the factor type.

Histrelin Hydrogel Implant ??? Valera

Valera Pharmaceuticals, formerly Hydro Med Sciences, is developing a once-yearly Histrelin Hydrogel Implant [Histrelin implant, LHRH-Hydrogel implant, RL 0903, SPD 424, Vantas], a subcutaneous (s.c.) reservoir device capable of long-term delivery of histrelin at constant release rates for the treatment of prostate cancer. Histrelin is a luteinising hormone-releasing hormone agonist (LHRH). A different formulation of the LHRH implant is currently in development for the treatment of central precocious puberty (CPP). On 4 September 2003, Hydro Med Sciences announced that it had changed its name to Valera Pharmaceuticals. Shire Pharmaceuticals had an option to market and distribute the histrelin implant outside the US, but in a realigned agreement announced in January 2002, Shire stated that HydroMed (now Valera) would be responsible for concluding the phase III studies, filing for regulatory approval and producing the implant, while also gaining marketing rights in the US. Shire has no further involvement in development, but retains an option to market and distribute the product outside the US. The product is available for rest-of-the-world licensing through Valera Pharmaceuticals' business development division. Paladin Labs has received the exclusive rights for the sale and marketing of histrelin hydrogel implant in Canada. Valera Pharmaceuticals will have the responsibility for manufacturing and completing development of the product. In July 2004, Paladin announced it had filed for regulatory approval with Health Canada for the treatment of prostate cancer. Phase III trials have been conducted and initially involved two open-labelled, randomised, parallel studies that compared the hydrogel implant with the active comparators, leuprorelin acetate 22.5 mg depot (TAP Pharmaceutical's Lupron Depot) and a 3-month implant of goserelin acetate (Astra Zeneca's Zoladex). However, because of financial constraints, HydroMed discontinued recruitment in a phase II European study and could not rationalise keeping the comparator arm of the phase III study. The US FDA then gave permission to continue the US part of the programme without the comparator arm, but with appropriate increases in the patient sample size. Patient enrolment in the phase III trial (US and Canada) was completed in July 2002. Valera Pharmaceuticals believes the product may have advantages over standard prostate cancer treatments including reduced costly surgical procedures, lower dosing, increased patient compliance and peace-of-mind, as well as potentially less cost to the patient. The phase III studies were completed in the second half of 2003.CPP arises from the increased release by the pituitary gland hormone gonadotropins and is characterised by an early onset of sexual development in pre-adolescents. Currently, the treatment of CPP involves injections of synthetic gonadotropic hormone-releasing factor agonists such as Supprelin (histrelin acetate) and TAP Pharmaceutical's Lupron Depot-Red (leuprolide acetate) every 28 days, a potentially painful procedure. This treatment inhibits pituitary release of gonadotropins. Valera's histrelin implant is a compact, removable subcutaneous implant that can be applied under a local anaesthetic in doctor's surgery.

In vivo degradability of hydrogels prepared from different gelatins by various cross-linking methods

This study is an investigation to evaluate the in vivo degradation of gelatin hydrogels in terms of their number of cross-links. Various hydrogels were prepared from acidic gelatin, extracted from bovine bone, porcine skin or fish scale, and basic gelatin, extracted from porcine skin, through four types of cross-linking methods, i.e., glutaraldehyde (GA) or dehydrothermal treatment and ultraviolet (UV) or electron beam irradiation. The water content of hydrogels and their number of cross-links, calculated from the tensile modulus of hydrogels, were evaluated as the measure of hydrogel cross-linking extent. Following subcutaneous implantation of 125I-labeled gelatin hydrogels into mice, the radioactivity remaining was measured at different time intervals to assess the in vivo degradability of hydrogels. Irrespective of the gelatin type and cross-linking method, a good correlation was found between the in vivo degradability of hydrogels and their number of cross-links, which is different from the correlation to their water content. This finding indicates that the degradability of hydrogels is governed by their number of cross-links.

Study of the calcification of PHEMA hydrogels using a two compartment permeation cell

To simulate the process of calcification in hydrogel implants, particularly calcification inside hydrogels, in vitro experiments using two compartment permeation cells have been performed. PHEMA hydrogel membranes were synthesized by free radical polymerization in bulk. The permeability and diffusion coefficient for Ca 2+ ions at 37 °C were determined using Fick's laws of diffusion. It was evident that Ca 2+ ions either from CaCl 2 or SBF solutions may diffuse through PHEMA hydrogel membranes. The formation of calcium phosphate deposits inside the hydrogel was observed and attributed to a heterogeneous nucleation from diffusing calcium and phosphate ions. The morphology of the deposits both on the surface and inside the hydrogels was found to be similar, i.e. spherical aggregates with a diameter of less than one micron.

Blood vessel formation after soft-tissue implantation of hyaluronan-based hydrogel supplemented with copper ions

The possibility of ameliorating bone healing of implanted bone allografts is a field of great interest. Early vascular invasion is a key factor in bone allograft incorporation. It is well known that copper ions (Cu 2+) show a proangiogenic action favouring the development of new vessels. In this work a hyaluronan based 50% hydrogel (Hyal-50%) was enriched with (Cu 2+) and its proangiogenic activity was evaluated. Fifteen Sprague Dawley female rats were submitted to the subcutaneous implantation of Hyal-50%, freeze-dried bone allografts, Hyal-50%-Cu 2+, freeze-dried bone allografts plus Hyal-50% and freeze-dried bone allografts plus Hyal-50%-Cu 2+. One month later, histomorphometric analysis evidenced the presence of a fibrous-reactive capsule around all specimens showing significant differences among groups ( p<0.0005). The highest thickness of the fibrous capsule was found around the freeze-dried bone implants ( p<0.05); as well as the Hyal-50%-Cu 2+ plus freeze-dried bone (15.2%, p<0.05) and Hyal 50% plus freeze-dried bone (21.4%, p<0.0005) implants showed a significant higher thickness compared with Hyal 50% and Hyal-50%-Cu 2+. Statistical analysis showed a significant ( p<0.01) higher vascular density in Hyal- 50%-Cu 2+ and Hyal-50%-Cu 2+ plus freeze-dried bone group when compared to other groups. The present preliminary results suggest the advantages offered by the combined use of a well-known biocompatible and tissue healing promoting material (Hyal-50%) and a new technique that consists of stimulating tissue vascularization using Cu 2+ and that bone allograft incorporation may benefit from this technology.

Simple Methods for Staining Chitosan in Biotechnological Applications

Chitosan is a naturally abundant cationic polysacchaside with unique physicochemical properties resulting in its use in a vast array of biomedical applications, including wound repair, drug delivery, and tissue engineering. However, despite numerous and diverse studies investigating its use, there have been no detailed reports describing specific staining methods for cell culture and histopathological studies using chitosan based materials. Here, we describe methods for staining chitosan in both cell culture and within paraffin sections. Procedural models used included identifying chitosan within in vitro whole blood clots, and culture wells, and in vivo chitosan hydrogel implants in multiple anatomical sites. First, a staining process for identifying chitosan was optimized using 0.03% Cibacron Brilliant Red-3BA. A second sensitive and versatile method using 0.01% Fast Green in conjunction with the known Safranin-O Method was demonstrated and may prove to be a key advancement in the histological study of chitosan-based biotechnological products. The method described here is broadly applicable to histological in situ detection of chitosan scaffolds of multiple deacetylation level and of variable fabrication. (The J Histotechnol 27:31, 2004)Submitted: September 30, 2003; Accepted: December 10, 2003

Stimulation of in vivo angiogenesis by cytokine-loaded hyaluronic acid hydrogel implants

Crosslinked hyaluronic acid (HA) hydrogels were evaluated for their ability to elicit new microvessel growth in vivo when preloaded with one of two cytokines, vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF). HA film samples were surgically implanted in the ear pinnas of mice, and the ears retrieved 7 or 14 days post implantation. Histologic analysis showed that all groups receiving an implant demonstrated significantly more microvessel density than control ears undergoing surgery but receiving no implant ( p<0.01). Moreover, aqueous administration of either growth factor produced substantially more vessel growth than an HA implant with no cytokine. However, the most striking result obtained was a dramatic synergistic interaction between HA and VEGF. Presentation of VEGF in crosslinked HA generated vessel density of NI=6.7 at day 14, where NI is a neovascularization index defined below, more than twice the effect of the sum of HA alone ( NI=1.8) plus VEGF alone ( NI=1.3). This was twice the vessel density generated by co-addition of HA and bFGF ( NI=3.4, p<0.001). New therapeutic approaches for numerous pathologies could be notably enhanced by the localized, synergistic angiogenic response produced by release of VEGF from crosslinked HA films.

Controlled release by biodegradable hydrogels enhances the ectopic bone formation of bone morphogenetic protein

The objective of this study is to develop a carrier for the controlled release of bone morphogenetic protein-2 (BMP-2) suitable for enhancement of the bone regeneration activity. Hydrogels with different water contents were prepared through glutaraldehyde crosslinking of gelatin with an isoelectric point of 9.0 under varied reaction conditions. Following subcutaneous implantation of the gelatin hydrogels incorporating 125I-labeled BMP-2 into the back of mice, the in vivo retention period of BMP-2 prolonged with a decrease in the water content of hydrogels used, although every time period was much longer than that of BMP-2 solution injection. Ectopic bone formation studies demonstrated that the alkaline phosphatase (ALP) activity and osteocalcin content around the implanted site of BMP-2-incorporated gelatin hydrogels were significantly high compared with those around the injected site of BMP-2 solution. The values became maximum for the gelatin hydrogel incorporating BMP-2 with a middle period of BMP-2 retention, while bone formation was histologically observed around the hydrogel incorporating BMP-2. The ALP activity was significantly higher than that of the collagen sponge incorporating BMP-2. We concluded that the controlled release technology of BMP-2 for a certain time period was essential to induce the potential activity for bone formation.

In vivo bone and soft tissue response to injectable, biodegradable oligo(poly(ethylene glycol) fumarate) hydrogels

This study was designed to assess in vivo bone and soft tissue behavior of novel oligo(poly(ethylene glycol) fumarate) (OPF) hydrogels using a rabbit model. In vitro degradation of the OPF hydrogels was also investigated in order to compare with in vivo characteristics. Four groups of OPF hydrogel implants were synthesized by alternation of crosslinking density, poly(ethylene glycol) (PEG) block length of OPF, and cell-binding peptide content. The in vitro degradation rate of OPF hydrogels increased with decreasing crosslinking density of hydrogels, which was characterized by measuring weight loss and swelling ratio of hydrogels and medium pH change. Examination of histological sections of the subcutaneous and cranial implants showed that an uniform thin circumferential fibrous capsule was formed around the OPF hydrogel implants. Quantitative evaluation of the tissue response revealed that no statistical difference existed in capsule quality or thickness between implant groups, implantation sites or implantation times. At 4 weeks, there was a very limited number of inflammatory and multinuclear cells at the implant–fibrous capsule interface for all implants. However, at 12 weeks, OPF hydrogels with PEG block length of number average molecular weight 6090±90 showed extensive surface erosion and superficial fragmentation that was surrounded by a number of inflammatory cells, while OPF hydrogels with PEG block length of number average molecular weight 930±10 elicited minimal degradation. Constant fibrous capsule layers and number of inflammatory cells were observed regardless of the incorporation of cell-binding peptide and crosslinking density of OPF hydrogels with PEG block length of number average molecular weight 930±90. These results confirm that the degradation of implants can be controlled by tailoring the macromolecular structure of OPF hydrogels. Additionally, histological evaluation of implants proved that the OPF hydrogel is a promising material for biodegradable scaffolds in tissue engineering.

Long-term effects of polyacrylamide hydrogel on human breast tissue.

Polyacrylamide hydrogel is an atoxic, stable, nonresorbable sterile watery gel consisting of approximately 2.5% cross-linked polyacrylamide and nonpyrogenic water. Polyacrylamide hydrogel is widely used in ophthalmic operations, drug treatment, food packaging products, and water purification. In the former Soviet Union, polyacrylamide hydrogel has been used in plastic and aesthetic surgery for more than 10 years, and Kiev City Hospital treats approximately 300 women a year for breast augmentation using the polyacrylamide hydrogel Interfall (Contura SA, Montreux, Switzerland). Capsule shrinkage following these injections has never been observed. The authors examined breast tissue samples from a total of 27 women who had polyacrylamide hydrogel injected at Kiev City Hospital up to 8 years and 10 months earlier. Age at operation, duration of polyacrylamide hydrogel implantation, history of possible side effects to the gel injection, other intercurrent diseases, the reason for present open breast operation, and breast palpation findings before operation were in each case compared with the histological findings on samples taken from breast tissue bordering the gel. The gel presented itself as a dark violet, homogenous mass with a rounded or ragged outline in large or medium-size deposits and as elongated strands, which mimicked the extracellular matrix, in small deposits. Histological findings of the breast tissue bordering the gel showed three different patterns: large collections of gel gave rise to a thick, soft-looking cellular membrane of macrophages and foreign-body giant cells; medium-size deposits were surrounded by just a thin layer of macrophages; and small deposits were not associated with any reaction in the surrounding tissue. Projections of the cellular soft membrane, known as granulomas, were seen in six patients. The granulomas were composed of macrophages, foreign-body giant cells, lymphocytes, and blood cells. A thin layer of fibrous connective tissue was occasionally present around the foreign-body membrane, but the thick fibrous capsule, which has been described in connection with silicone implants, was completely absent. The gel changes could be correlated to neither time since gel injection nor a history of recent injury or inflammation. It is concluded that the polyacrylamide hydrogel Interfall, which has been used in the former Soviet Union, is stable over time, nondegradable, confined to the breast, and diffusion and migration resistant. When the hydrogel is injected in medium-size or large quantities a cellular foreign-body reaction occurs, but in small amounts it is capable of splitting up individual connective tissue fibers and fat cells, substituting for the extracellular connective tissue matrix without eliciting any foreign-body reaction. As far as these data are concerned, polyacrylamide hydrogel is well tolerated by the breast and does not give rise to severe fibrosis, pain, or capsule shrinkage. However, to determine safety with more certainty, a larger sample size would be necessary.

In situ accelerated degradation of polyoxyethylene/poly(ε-caprolactone) multiblock copolymer by moderate thermal treatment

Alternating amphiphilic multiblock copolymers, consisting of polyoxyethylene (POE) and poly(ε-caprolactone) (PCL) of various lengths, were synthesized by a polycondensation reaction between dicarboxylated PEG and dihydroxyl PCL. The polymer formed a physical hydrogel by PCL crystallization. For in vitro hydrolysis in phosphate-buffered saline solution, the change of molecular weight depended on the composing block length of POE. The polymer with longer POE showed a faster decline in molecular weight. The mass remaining at the end of two weeks at 25°C was more than 95 wt%. However, when the swollen hydrogels were exposed to temperatures slightly above PCL melting point for 30 min, the degradation rate was accelerated and the mass remaining dropped to less than 10 wt% in one week. In vivo degradation after hydrogel implantation, the polymer degraded as under in vitro. However, the implant irradiated with infrared (IR) accelerated its degradation similar to a treatment with elevated temperature.

Influence of local complications on capsule formation around model implants in a rat model.

We studied the capsule formation around various filled breast implants and other related changes in distant organs (e.g., liver, spleen, lymph nodes) in a rat model 3 and 6 months after implantation. Model implants, one per rat, (filled with saline, n = 19; silicone, n = 14; cohesive silicone, n = 17; and hydrogel, n = 19) were implanted subcutaneous in the lower back of rats. The animals were sacrificed regularly after 3 and 6 months of implantation or when wound defects occurred. The capsules and organs were examined histologically, and immunohistology of the capsules was performed. A monoclonal antibody specific for AIF-1 (allograft inflammatory factor 1) was used to detect activated macrophages. Wound defects occurred most frequently after implantation of saline and hydrogel implants. Increased capsule thickness was associated with increased grade of inflammation, fibrosis, and the type of implant filling. There was a significant positive correlation between capsule thickness, presence of chronic inflammation, and AIF-1-positive macrophages (p < 0.0001), indicating that inflammation plays an important role in capsule formation. Remarkably, saline and silicone implants (in absence of local complications) cause only a blande slight fibrosis in capsules after 6 months of implantation, whereas capsules around cohesive silicone implants exhibited a more severe fibrosis with an increased capsule thickness. Most importantly, hydrogel seems to be most potent to induce an inflammatory infiltrate with AIF-1 expressing macrophages at the implantation site, independent of implantation time, and capsules also produced a significant increase in thickness after 6 months.

Dégonflement des prothèses mammaires pré-remplies de sérum physiologique ou d’hydrogel. Résultats et analyse d’une série de 650 patientes opérées

Subject : The main mechanical side effect of saline or hydrogel filled implants is deflation. The aim of this study was to analyse the prosthetic deflation rate in the last 7 years in the plastic surgery unit of Toulouse. Patients and methods : We tracked 650 patients operated on between july 1993 and july 2000 (representing 1117 primary implants) which we separated in two groups: the first group contained patients in need of breast reconstruction; the second group contained all the patients with implants placed for aesthetic or breast asymetry reasons. For each of the two groups we determined the number and the type of implants, as well as the rate and the mean delay after which deflation occurred. Results : During this period, we’ve determined that : • rate of deflation of group 1 (reconstruction) is highest than group 2 (aesthetic), despite sort of implant ; • rates of deflation of pre-filled hydrogel implants are highest than rates of deflation of pre-filled saline implants. Discussion : Only a few series concerning implants deflation have been described in the litterature. We can find a large difference in results which vary from 2 to 76%. We were surprised by the result of our series with a rate of deflation up to 15% with a medium follow-up 5 years in both groups and a mean delay before the fourth year. Deflation’s factors are numerous: type of sterilisation, rippling, texture, valve’s incompetence, prosthetic patch, guarantee controle and iatrogenic causes. Because the silicone gel implants (the one uncomplicated by deflation) were taken off the french market, the saline implants tried to supplant them but without satisfactory results. Conclusions : With the unacceptable rate deflation of implants in our study, the return in the french market of silicone gel implants seems us an acceptable alternative.

Promoted growth of murine hair follicles through controlled release of basic fibroblast growth factor.

This study is an investigation to evaluate how the controlled release of basic fibroblast growth factor (bFGF) affects the hair follicle growth of mice in different hair cycle stages: second anagen and second telogen. bFGF was incorporated into biodegradable gelatin hydrogels for its controlled release. After subcutaneous implantation of gelatin hydrogels incorporating 0, 0.7, 7, and 70 microg of bFGF or injection of 0 and 70 microg of free bFGF into the backs of mice, hair follicle growth was evaluated photometrically and histologically on the basis of three parameters: skin color of the reverse side of the implanted or injected site, skin thickness, and area occupied by hair follicle tissue. For mice in second anagen, the darkness of the reverse side of skin implanted with gelatin hydrogel incorporating 7 microg of bFGF was significantly higher than that of skin injected with 70 microg of bFGF 10 days after bFGF application. Implantation of gelatin hydrogel incorporating bFGF enabled the hair follicles to increase the area occupied in skin tissue to a significantly greater extent than in other groups, whereas no effect on skin thickness was observed. bFGF-free, empty gelatin hydrogels did not affect hair follicle growth. Moreover, hair shaft length was significantly elongated by gelatin hydrogel incorporating 7 microg of bFGF, in marked contrast to other agents. The skin of telogen mice receiving gelatin hydrogel incorporating 7 microg of bFGF did not show any change in darkness of reverse skin side or skin thickness, but a significant increase in the size of hair follicles 10 days later. These results indicate that the controlled release of bFGF positively affects the hair growth cycle of mice.

Development of hydrogel implants for urinary incontinence treatment

Hydrogel implants for urinary incontinence treatment based on HEMA supplemented with 10% methacrylic acid have been developed. The swelling properties of implants were tested in vitro and in vivo after implantation to laboratory mice. Biocompatibility has been determined by incubation of implants in tissue culture, by histological examination of adjacent tissues after subcutaneous application of implants to laboratory mouse in a long-term experiment, and by flow cytometry examination of blood cells. The swelling of hydrogel implants was completed in 6–24 h. There was no effect on in vitro growth of cells incubated with implants. In mice, implants were well tolerated without any sign of inflammatory reaction. The material allows an elastic compression of urethra compensating a damaged sphincter after trans-urethral sub-mucosal implantation of hydrogel cylinders.