Salmon fibrinogen and chitosan scaffold for tissue engineering: in vitro and in vivo evaluation

3D fibrous scaffolds have received much recent attention in regenerative medicine. Use of fibrous scaffolds has shown promising results in tissue engineering and wound healing. Here we report the development and properties of a novel fibrous scaffold that is useful for promoting wound healing. A scaffold made of salmon fibrinogen and chitosan is produced by electrospinning, resulting in a biocompatible material mimicking the structure of the native extracellular matrix (ECM) with suitable biochemical and mechanical properties. The scaffold is produced without the need for enzymes, in particular thrombin, but is fully compatible with their addition if needed. Human dermal fibroblasts cultured on this scaffold showed progressive proliferation for 14 days. Split-thickness experimental skin wounds treated and untreated were compared in a 10-day follow-up period. Wound healing was more effective using the fibrinogen-chitosan scaffold than in untreated wounds. This scaffold could be applicable in various medical purposes including surgery, tissue regeneration, burns, traumatic injuries, and 3D cell culture platforms.

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Large-Scale Fabrication of Robust Artificial Skins from a Biodegradable Sealant-Loaded Nanofiber Scaffold to Skin Tissue via Microfluidic Blow-Spinning

Given that many people suffer from large-area skin damage, skin regeneration is a matter of high concern. Here, an available method is developed for the formation of large-area robust skins through three stages: fabrication of a biodegradable sealant-loaded nanofiber scaffold (SNS), skin tissue reconstruction, and skin regeneration. First, a microfluidic blow-spinning strategy is proposed to fabricate a large-scale nanofiber scaffold with an area of 140 cm × 40 cm, composed of fibrinogen-loaded polycaprolactone/silk fibroin (PCL/SF) ultrafine core–shell nanofibers with mean diameter of 65 nm. Then, the SNS forms, where the gelling reaction of fibrin sealant occurs in situ between thrombin and fibrinogen on PCL/SF nanofiber surface, to promote the migration and proliferation of fibroblasts, accelerating skin regeneration. Through an in vivo study, it is shown that the SNS can rapidly repair acute tissue damage such as vascular bleeding and hepatic hemorrhage, and also promote angiogenesis, large-area abdominal wall defect repair, and wound tissue regeneration for medical problems in the world. Besides, it avoids the risk of immune rejection and secondary surgery in clinical applications. This strategy offers a facile route to regenerate large-scale robust skin, which shows great potential in abdominal wall defect repair.     

Tissue spinal cord response in rats after implants of polypyrrole and polyethylene glycol obtained by plasma

Most of the biomaterials used nowadays for the reconstruction of the spinal cord (SC) tissue after an injury, tested in animals, have obtained modest results. This work presents a study about the compatibility of two novel, non-biodegradable, semi-conductive materials, obtained by plasma polymerization: iodine-doped pyrrole (PPy/I) and pyrrole-polyethylene glycol (PPy/PEG). Both polymers, separately, were implanted in the SC tissue of rats after a transection. Prior to implantation, the elemental composition and the physico-chemical properties of polymers were studied by electron scanning microscopy, IR Spectroscopy and thermogravimetric analysis. We used adult female Long Evans rats, subjected to SC transection. Animals were randomized to be allocated in one of the treatment groups and were killed four weeks after the lesion for histology study. Results showed that both implants were integrated to the SC tissue, as inflammatory and gliotic responses, similar to those observed in the control group, and rejection of the implant, were not evident. Moreover, the immediate effect of PPy/I or PPy/PEG in the injured SC prevented secondary tissue destruction, as compared to non-implanted control animals. In conclusion, implants of semi-conductive polymers were well-tolerated and integrated favorably to SC tissue after transection     

Interleukin-6 collection through long-term implanted microdialysis sampling probes in rat subcutaneous space

Microdialysis sampling is a method that has promise for collection of important signaling proteins such as cytokines that are involved in every aspect of the immune response. The objective of this study was to determine the role of membrane and tissue alterations on the reduction of interleukin-6 (IL-6) relative recovery of microdialysis probes implanted for 3 and 7 days versus probes implanted on day 0 (acute implant or control probe). Lipopolysaccharide (LPS), a bacterial endotoxin, was used to elicit IL-6 production in the animals. Within the same animal, the recovery of IL-6 through control probes implanted the day of sample collection was compared to the 3- or 7-day implanted probes. Two hours post-LPS administration, the IL-6 concentrations obtained from either the 3-day or 7-day implanted probe were reduced by more than 8-fold when compared to the control probe. The IL-6 concentrations obtained for the 3-day versus control probes 2-h post-LPS injection were 730 +/- 310 and 6440 +/- 1550 pg/mL (mean +/- SD, n = 3), respectively. For the 7-day implant, the IL-6 concentration in the dialysis probe obtained at 2-h post-LPS injection was 990 +/- 590 versus 5520 +/- 1430 pg/mL (mean +/- SD, n = 3) for the control. In vitro recovery experiments and scanning electron microscopy images combined with the in vivo data suggest that the decreased IL-6 content in the dialysate was caused principally by tissue alterations or tissue encapsulation rather than membrane blockage with biological components (membrane biofouling).     

A Comparative Study of the In Vitro and In Vivo Release of Dexamethasone from a Spray-On Bandage and Timed Release Aerosol

The formulation of several dexamethasone topical delayed release aerosol preparations was studied. Ethylcellulose and tributyl citrate were the film-forming agent and plasticizer, respectively, for the spray-on bandage formulation. The aerosol timed release preparation contained dexamethasone microcapsules suspended in a fluorocarbon aerosol propellant by isopropyl myristate and fumed silica. Both preparations were evaluated using an in vitro method which measured the release of dexamethasone hourly for eight hours. In vitro studies showed that each of the formulations delayed the release of dexamethasone. In the in vivo tests aerosols were sprayed on the unabraded back area of rabbits and the increased 17 - hydroxycorticosteriod urine levels at 24, 48, and 72 hours indicated dexamethasone absorption. In vivo studies indicated that absorption did not occur with the timed release preparation containing dexamethasone microcapsules. However, dexamethasone from the spray-on bandage preparation was absorbed over 72 hours. A commercially marketed topical dexamethasone cream was used for comparison in evaluating the two experimental formulations; however, in vivo studies showed that no absorption occurred with this preparation.

In recent years, a great deal of work has been directed towards the application of medicated polymeric films or tissue adhesives onto the skin to treat minor dermatological problems or serious skin wounds. Among the factors to be considered are: incorporation of a specific active ingredient, the mode of application and the dosage form. Lange and Fang (1,2) developed spray-on bandages using water soluble resins and water as the solvent. Fischl (3) evaluated the effectiveness of a cyanoacrylate monomer in closing skin incisions without affecting wound healing. Bhaskar and Cutright (4) showed that butyl cyanoacrylate could be successfully used as a surface dressing while reducing the degree of inflammation. Sciarra and Gidwani (5,6) reported on the release of gentian violet from selected polymer and plasticizer combinations and established various polymer-plasticizer combinations which could be applied as an aerosol spray. Other studies (7,8) have shown that ethylcellulose and a thermoplastic polyamide resin have potential use in spray-on bandage formulations.

The results indicated that the anti-infectives were released from the films and the spray-on bandages reduced the degree of infection about the wound.

The process of microencapsulation has been applied to various industrial and medical uses. Microcapsules can be prepared so that the encapsulated material will be released slowly. There are various methods of microencapsulation including coacervation, phase separation, interfacial polymerization, an electrostatic method, and vacuum metalization and they have been successfully used with selected drugs (9-13).

The purpose of this study was to develop and evaluate different aerosol formulations containing a therapeutic agent which can be slowly released. In vitro and in Vivo systems were used to evaluate the release and absorption of the drug in the test animals.     

Tissue reactions to bioabsorbable ciprofloxacin-releasing polylactide-polyglycolide 80/20 screws in rabbits’ cranial bone

The aim of this study was to assess tissue reactions to bioabsorbable self-reinforced ciprofloxacin-releasing polylactide/polyglycolide (SR-PLGA) 80/20 screws in rabbits' cranial bone. Two screws were implanted in each rabbit, one screw on either side of the sagittal suture (n = 28 rabbits). Animals were sacrificed after 2, 4, 8, 16, 24, 54 and 72 weeks, four animals per group. On histological examination the number of macrophages, giant cells, active osteoblasts and fibrous tissue layers were assessed and degradation of the screws was evaluated. At 2 weeks, the highest number of macrophages and giant cells were seen near the heads of the screws. After 4 and 8 weeks, the number of giant cells decreased but that of macrophages decreased from 16 weeks and on. Screws were surrounded by fibrous tissue capsule that progressively was growing in thickness by time. Active osteoblasts were seen around the shaft of the screws with the highest number seen at 4 weeks postoperatively. At 16 weeks, compact fragmentation of the screw heads was seen with macrophages seen inside the screw matrices. After 24 weeks, no polarization of the screws was seen. After one year, PLGA screws had been replaced by adipose tissue, fibrous tissue and "foamy macrophages" which had PLGA particles inside them. After 1(1/2) years, the amount of biomaterial remaining had decreased remarkably. The particles of biomaterial were inside "foamy macrophages." Ciprofloxacin-releasing SR-PLGA 80/20 screws elicited a mild inflammatory reaction but did not interfere with osteoblast activity. No complications were seen when implanted in cranial bone of rabbit.     

Enhanced mesenchymal stromal cell recruitment via natural killer cells by incorporation of inflammatory signals in biomaterials

An exacerbated inflammatory response questions biomaterial biocompatibility, but on the other hand, inflammation has a central role in the regulation of tissue regeneration. Therefore, it may be argued that an ‘ideal’ inflammatory response is crucial to achieve efficient tissue repair/regeneration. Natural killer (NK) cells, being one of the first populations arriving at an injury site, can have an important role in regulating bone repair/regeneration, particularly through interactions with mesenchymal stem/stromal cells (MSCs). Here, we studied how biomaterials designed to incorporate inflammatory signals affected NK cell behaviour and NK cell–MSC interactions. Adsorption of the pro-inflammatory molecule fibrinogen (Fg) to chitosan films led to a 1.5-fold increase in adhesion of peripheral blood human NK cells, without an increase in cytokine secretion. Most importantly, it was found that NK cells are capable of stimulating a threefold increase in human bone marrow MSC invasion, a key event taking place in tissue repair, but did not affect the expression of the differentiation marker alkaline phosphatase (ALP). Of significant importance, this NK cell-mediated MSC recruitment was modulated by Fg adsorption. Designing novel biomaterials leading to rational modulation of the inflammatory response is proposed as an alternative to current bone regeneration strategies.     

Development and preparation of a low-immunogenicity porcine dermal scaffold and its biocompatibility assessment

Acellular dermal matrix (ADM) has been widely used in repair and reconstruction of tissue defect. Therapeutic effect of porcine ADM (PADM) is inferior to that of human ADM (HADM). Relatively high immunogenicity and the resulting strong inflammatory response are major issue in application of PADM. We therefore treated reticular layer PADM (Rl-PADM) with matrix metalloproteinase-7 (MMP-7) and obtained a low-immunogenicity porcine dermal scaffold (LIPDS). Highly immunogenic components, tissue structure, cytocompatibility, and postgrafting histological changes of LIPDS were further investigated. Compared with Rl-PADM, LIPDS showed that the epithelial root sheath, cell debris, laminin, and type IV collagen were almost entirely removed, the structure remained normal, and the interfibrous space was relatively enlarged. Cytocompatibility of LIPDS was similar to that of HADM but superior to Rl-PADM. With regard to the extent of tissue ingrowth in terms of host fibroblasts infiltration and vascularization, LIPDS exhibited clear advantages over Rl-PADM after they had been subcutaneously transplanted in a rat model. In addition, no excessive inflammatory response was observed in LIPDS group up to 28 days postgraft, and the morphosis of collagenous fibers kept essentially normal. However, there were stronger inflammatory response and obvious collagen spallation in Rl-PADM group. The processes of integration and remodeling after the LIPDS grafting were similar to those of a normal wound healing response. The LIPDS graft was vascularized at a relatively high speed. Thus, as an implantable scaffold material, LIPDS is a superior template for guiding tissue regeneration and remodeling.     

Bone tissue formation in sheep muscles induced by a biphasic calcium phosphate ceramic and fibrin glue composite

Some biomaterials are able to induce ectopic bone formation in muscles of large animals. The osteoinductive potential of macro- micro-porous biphasic calcium phosphate (MBCP) ceramic granules with fibrin glue was evaluated by intramuscular implantation for 6 months in six adult female sheep. The MBCP granules were 1–2 mm in size and were composed of hydroxyapatite (HA) and beta-tricalcium phosphate (β-TCP) in a 60/40 ratio. The fibrin glue was composed of fibrinogen, thrombin and other biological factors. After 6 months of implantation in the dorsal muscles of sheep, the explants were rigid. Histology, back-scattered electron microscopy and micro-computed tomography of the implants indicated that approximately 12% of mineralized bone had formed in between the MBCP granules. The ectopic bone appeared well-mineralized with mature osteocytes and Haversian structures. In addition, the number and thickness of bone trabeculae formed in between the MBCP particles were similar to those measured in trabecular bone in sheep. The overall results therefore confirmed the formation of well-mineralized ectopic bone tissue after intramuscular implantation of MBCP/fibrin glue composites. These bone substitutes exhibiting osteoinductive properties could be used for the reconstruction of large bone defects.     

Characterisation of environmentally exposed cement-based stabilised/solidified industrial waste

A metal-plating waste filter cake treated by stabilisation/solidification (S/S) using ordinary Portland cement (OPC) and pulverised fuel ash (PFA) has been characterised after exposure to the environment in SE England for approximately 10 years. The surface region ( approximately 5cm) was severely degraded, extensively carbonated and had reduced acid neutralisation capacity (ANC) compared to bulk samples. Large 'plate-like' deposits of predominantly calcium hydroxide with a calcium carbonate upper layer were found close to, but below the surface of the exposed S/S waste. Calcium zinc hydroxide (Ca(Zn(OH)(3))(2).2H(2)O) was the major crystalline phase found in the S/S waste in the region below the calcium hydroxide plates (10-15cm). Samples taken from the bulk of the environmentally exposed S/S waste, at a depth of approximately 0.5m, were more amorphous, contained no readily identifiable crystalline phases and had negligible strength but retained high acid neutralisation capacity. Metal analysis of homogenised samples taken from different depths into the S/S waste indicated a reduction in the concentration of heavy metals, such as Zn, Fe and Cr, in the top 5cm of the S/S waste and an increase in concentration of these metals in bulk samples. The majority of crystalline mineral phases detected in the 28-day samples were not identified in the 10-year-old samples.     

Microalgae-Based Biohybrid Microrobot for Accelerated Diabetic Wound Healing

A variety of wound healing platforms have been proposed to alleviate the hypoxic condition and/or to modulate the immune responses for the treatment of chronic wounds in diabetes. However, these platforms with the passive diffusion of therapeutic agents through the blood clot result in the relatively low delivery efficiency into the deep wound site. Here, a microalgae-based biohybrid microrobot for accelerated diabetic wound healing is developed. The biohybrid microrobot autonomously moves at velocity of 33.3 µm s⁻¹ and generates oxygen for the alleviation of hypoxic condition. In addition, the microrobot efficiently bound with inflammatory chemokines of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) for modulating the immune responses. The enhanced penetration of microrobot is corroborated by measuring fibrin clots in biomimetic wound using microfluidic devices and the enhanced retention of microrobot is confirmed in the real wounded mouse skin tissue. After deposition on the chronic wound in diabetic mice without wound dressing, the wounds treated with microrobots are completely healed after 9 days with the significant decrease of inflammatory cytokines below 31% of the control level and the upregulated angiogenesis above 20 times of CD31⁺ cells. These results confirm the feasibility of microrobots as a next-generation platform for diabetic wound healing.     

Examining porous bio-active glass as a potential osteo-odonto-keratoprosthetic skirt material

Bio-active glass has been developed for use as a bone substitute with strong osteo-inductive capacity and the ability to form strong bonds with soft and hard tissue. The ability of this material to enhance tissue in-growth suggests its potential use as a substitute for the dental laminate of an osteo-odonto-keratoprosthesis. A preliminary in vitro investigation of porous bio-active glass as an OOKP skirt material was carried out. Porous glass structures were manufactured from bio-active glasses 1-98 and 28-04 containing varying oxide formulation (1-98, 28-04) and particle size range (250–315 μm for 1-98 and 28-04a, 315–500 μm for 28-04b). Dissolution of the porous glass structure and its effect on pH was measured. Structural 2D and 3D analysis of porous structures were performed. Cell culture experiments were carried out to study keratocyte adhesion and the inflammatory response induced by the porous glass materials. The dissolution results suggested that the porous structure made out of 1-98 dissolves faster than the structures made from glass 28-04. pH experiments showed that the dissolution of the porous glass increased the pH of the surrounding solution. The cell culture results showed that keratocytes adhered onto the surface of each of the porous glass structures, but cell adhesion and spreading was greatest for the 98a bio-glass. Cytokine production by all porous glass samples was similar to that of the negative control indicating that the glasses do not induce a cytokine driven inflammatory response. Cell culture results support the potential use of synthetic porous bio-glass as an OOKP skirt material in terms of limited inflammatory potential and capacity to induce and support tissue ingrowth.     

Influencing biophysical properties of fibrin with buffer solutions

Fibrin has been proposed as cell scaffold for numerous tissue engineering applications. While most of the studies have focused on fibrinogen and thrombin, other components of fibrin can also affect its properties. The present study aimed to evaluate the effects of buffer solution composition on fibrin biophysical properties. Fibrin scaffolds were synthesized with different calcium, chloride, and factor XIII (FXIII) final concentrations. Light transmission was determined as a relative, semi-quantitative estimator of fiber structure differences, and two compositions, resulting in translucent and opaque gels, were tested for mechanical and biological properties. Gels were seeded with mouse mesenchymal cells, C3H10T1/2, or bovine bone marrow-derived mesenchymal stromal cells and cultured up to 10 or 24 days, before cell number, morphology and distribution were evaluated. Calcium increased gel opacity (i.e., fiber thickness), while chloride and FXIII decreased it. Opaque gels displayed a fluid-like viscous behavior while translucent gels showed improved elastic properties. Both compositions supported survival of both cell types with opaque gels leading to better proliferation, but significant scaffold shrinkage after 17 days of culture. These results demonstrated that calcium, chloride, and FXIII modulate the biophysical properties of fibrin, and can be used to adjust mechanical and biological properties for tissue engineering applications.     

Analysis of rat plasma proteins desorbed from gold and methyl- and hydroxyl-terminated alkane thiols on gold surfaces

It is believed that adsorbed blood or plasma components, such as water, peptides, carbohydrates and proteins, determine key events in the concomitant inflammatory tissue response close to implants. The aim of the present study was to develop a procedure for the collection and analysis of minor amounts of proteins bound to solid metal implant surfaces. The combination of a sodium dodecyl sulfate washing method coupled with a polyacylamide gel electrophoretic protein separation technique (SDS–PAGE), Western blot and image analysis enabled the desorption, identification and semiquantification of specific proteins. The analyzed proteins were albumin, immunoglobulin G, fibrinogen and fibronectin. Concentration procedures of proteins were not required with this method despite the small area of the test surfaces. The plasma proteins were adsorbed to pure gold and hydroxylated and methylated gold surfaces, which elicit different tissue responses in vivo and plasma protein adsorption patterns in vitro. The image analysis revealed that the pure gold surfaces adsorbed the largest amount of total and specific proteins. This is in accordance with previous ellipsometry/antibody experiments in vitro. Further, the principles described for the protein analysis can be applied on implant surfaces ex vivo. ©©2000 Kluwer Academic Publishers     

Geomagnetic imprinting predicts spatio-temporal variation in homing migration of pink and sockeye salmon

Animals navigate using a variety of sensory cues, but how each is weighted during different phases of movement (e.g. dispersal, foraging, homing) is controversial. Here, we examine the geomagnetic and olfactory imprinting hypotheses of natal homing with datasets that recorded variation in the migratory routes of sockeye (Oncorhynchus nerka) and pink (Oncorhynchus gorbuscha) salmon returning from the Pacific Ocean to the Fraser River, British Columbia. Drift of the magnetic field (i.e. geomagnetic imprinting) uniquely accounted for 23.2% and 44.0% of the variation in migration routes for sockeye and pink salmon, respectively. Ocean circulation (i.e. olfactory imprinting) predicted 6.1% and 0.1% of the variation in sockeye and pink migration routes, respectively. Sea surface temperature (a variable influencing salmon distribution but not navigation, directly) accounted for 13.0% of the variation in sockeye migration but was unrelated to pink migration. These findings suggest that geomagnetic navigation plays an important role in long-distance homing in salmon and that consideration of navigation mechanisms can aid in the management of migratory fishes by better predicting movement patterns. Finally, given the diversity of animals that use the Earth''s magnetic field for navigation, geomagnetic drift may provide a unifying explanation for spatio-temporal variation in the movement patterns of many species.     

Development of salmon milt DNA/salmon collagen composite for wound dressing

This study aims to develop a novel wound dressing comprising salmon milt DNA (sDNA) and salmon collagen (SC). The sDNA/SC composites were prepared by incubating a mixture of an acidic SC solution, an sDNA solution, and a collagen fibrillogenesis inducing buffer (pH 6.8) containing a crosslinking agent (water-soluble carbodiimide) for gelation, and a subsequent ventilation-drying process to give sDNA/SC films. The conjugation between sDNA and SC were confirmed by sDNA-elution assay and fluorescence microscopy. The sDNA/SC films with various doses of sDNA (sDNA/SC weight ratios of 1:5, 1:10, and 1:20) were used for in vitro cell cultures to evaluate their growth potentials of normal human dermal fibroblasts (NHDF) and normal human epidermal keratinocytes (NHEK). It was found that NHDF proliferation was increased by sDNA conjugation, whereas NHEK proliferation was dose-dependently inhibited. In light of the in vitro results, the appropriate dose of sDNA for in vivo study was determined to be the ratio of 1:10. For the implantation in full-thickness skin defects in rat dorsal region, the sDNA/SC films were reinforced by incorporating them on a porous SC sponge, because the sDNA/SC films exhibited early contraction and inadequate morphologic stability when implanted in vivo. The regenerated tissue in the sDNA/SC sponge group showed similar morphology to native dermis, while the SC sponge group without sDNA showed epithelial overgrowth, indicating that additional sDNA could reduce epidermal overgrowth. Furthermore, blood capillary formation was significantly enhanced in the sDNA/SC sponge group when compared to the SC sponge group. In conclusion, the results suggest that the sDNA/SC composite could be a potential wound dressing for clinical applications.     

Microbubble-enhanced cavitation for noninvasive ultrasound surgery

Experiments were conducted to explore the potential of stabilized microbubbles for aiding tissue ablation during ultrasound therapy. Surgically exteriorized canine kidneys were irradiated in situ using single exposures of focused ultrasound. In each experiment, tip to eight separate exposures were placed in the left kidney. The right kidney was then similarly exposed, but while an ultrasound contrast agent was continually infused. Kidneys were sectioned and examined for gross observable tissue damage. Tissue damage was produced more frequently, by lower intensity and shorter duration exposures, in kidneys irradiated with the contrast agent present. Using 250-ms exposures, the minimum intensity that produced damage was lower in kidneys with microbubbles than those without (controls) in 10 of 11 (91%) animals. In a separate study using /spl sim/3200 W/cm/sup 2/ exposures, the minimum duration that produced damage was shorter after microbubbles were introduced in 11 of 12 (92%) animals. With microbubbles, gross observable tissue damage was produced with exposure intensity /spl ges//spl sim/800 W/cm/sup 2/ and exposure duration /spl ges/10 /spl mu/s. The overall intensity and duration tissue damage thresholds were reduced by /spl sim/2/spl times/ and /spl sim/100/spl times/, respectively. Results indicate that acoustic cavitation is a primary damage mechanism. Lowering in vivo tissue damage thresholds with stabilized microbubbles acting as cavitation nuclei may make acoustic cavitation a more predictable, and thus practical, mechanism for noninvasive ultrasound surgery.     

In vivo biocompatibility of radiation induced acrylamide and acrylamide/maleic acid hydrogels

In vitro swelling and in vivo biocompatibility of radiation induced acrylamide (AAm) and acrylamide/maleic acid (AAm/MA) hydrogels were investigated. The swelling kinetics of AAm and AAm/MA hydrogels of are investigated in distilled water, human serum and some simulated physiological fluids such as phosphate buffer at pH 7.4, glycine-HCl buffer at pH 1.1, physiological saline solution and, some swelling and diffusion parameters have been calculated. AAm and AAm/MA hydrogels were subcutaneously implanted in rats for up to 10 weeks and the tissue response to these implants was studied. Histological analysis indicated that tissue reaction at the implant site progressed from an initial acute inflammatory response characterized. No necrosis, tumorigenesis or infection was observed at the implant site up to 10 week. In vivo studies indicated that the radiation induced acrylamide and acrylamide/maleic acid hydrogels were found to be well-tolerated, non-toxic and highly biocompatible.