Histological, Histomorphometrical, and Biomechanical Studies of Bone-Implanted Medical Devices: Hard Resin Embedding.

The growing incidence of degenerative musculoskeletal disorders as well as lifestyle changes has led to an increase in the surgical procedures involving implanted medical devices in orthopedics. When studying implant/tissue interface in hard materials (i.e., metals or dense plastics) and/or in large bone segments, the hard plastic embedding of the intact undecalcified tissue envelope with the implant in situ is needed. The aim of this work is to describe the advances and the possibilities of high-temperature methyl methacrylate (MMA) embedding for the histological, histomorphometrical, and biomechanical assessment of bone-implanted medical devices. Unlike routine techniques, undecalcified bone processing histology, using high-temperature MMA, requires a complex and precise sample processing methodology and the availability of sophisticated equipment and software for both sample preparation and analyses. MMA embedding permits the evaluation of biological responses to the presence of implanted medical devices without implant removal, allowing simultaneous qualitative and quantitative histological evaluation, both static and dynamic histomorphometry, and biomechanical analyses not possible with tissue decalcification. MMA embedding, despite being a demanding procedure, is still preferred to other kinds of resin-based embedding because of its peculiar characteristics, which allow the study of samples of big dimensions also implanted with hard materials without reducing the sample or removing the material. Dynamic measurements are allowed together with biomechanical investigations at the bone-biomaterial interface, obtaining a comprehensive and precise evaluation of the safety and effectiveness of medical devices for orthopedic regenerative, reconstructive, and reparative surgery.

Link between estrogen deficiency osteoporosis and susceptibility to bone metastases: A way towards precision medicine in cancer patients.

Different fields of cancer management consider bone health to be of increasing clinical importance for patients: 1) presence of bone metastases in many solid tumors, 2) use of bone-targeted treatments in the reduction of bone metastasis, 3) effects of cancer treatment on reproductive hormones, critical for normal bone remodeling maintenance. Additionally, bone microenvironment is further complicated by the decline of ovarian sex steroid production and by the related increase in inflammatory factors linked to menopause, which result in accelerated bone loss and increased risk of osteoporosis (OP). Similarly, cancers and metastasis to bone showed a close relationship with sex hormones (particularly estrogen). Thus, these findings raise a question: Could pre-existing estrogen deficiency OP promote and/or influence cancer cell homing and tumor growth in bone? Although some preclinical and clinical evidence exists, it is mandatory to understand this aspect that would be relevant in the clinical theatre, where physicians need to understand the treatments available to reduce the risk of skeletal disease in cancer patients. This descriptive systematic review summarizes preclinical and clinical studies dealing with bimodal interactions between pre-existing estrogen deficiency OP and bone metastasis development and provides evidence supporting differences in tumor growth and colonization between healthy and OP status. Few studies evaluated the impact of estrogen deficiency OP on the susceptibility to bone metastases. Therefore, implementing biological knowledge, could help researchers and clinicians to have a better comprehension of the importance of pre- and post-menopausal bone microenvironment and its clinical implications for precision medicine in cancer patients.

A novel technique for decellularization of allogenic nerves and in vivo study of their use for peripheral nerve reconstruction.

Autografts represent the gold standard for peripheral nerve reconstruction but their limited availability, the discrepancy of nerve caliber, and long surgical times are drawbacks. Allografts have therefore become a valid alternative option. In particular, acellular nerve allografts (ANAs) rather than fresh allografts do not need immunosuppression and appear to be safe and effective based on recent studies. An innovative method was conceived to obtain ANAs, so as to speed up nerve decellularization, without compromising nerve architecture, and without breaking the asepsis chain. Several detergent-based techniques, integrated with sonication and mechanical stirring, were tested in vitro on rabbit nerves, to identify, by microscopy and immunohistochemistry, the most effective protocol in terms of cell lysis and cellular debris clearance, while maintaining nerve architecture. Furthermore, a pilot in vivo study was performed: ANAs were implanted into tibial nerve defects of three rabbits, and autografts, representing the gold standard, in other three animals. Twelve weeks postoperatively, rabbits were clinically evaluated and euthanasized; grafts were harvested and microscopically and histomorphometrically analyzed. The method proved to be effective in vitro: the treatment removed axons, myelin and cells, without altering nerve architecture. The in vivo study did not reveal any adverse effect: animals maintained normal weight and function of posterior limb during the entire experimental time. A mild fibrotic reaction was observed, macrophages and leukocytes were rare or absent; ANAs regenerated fascicles and bundles were comparable versus autografts. Based on these results, this decellularization protocol is encouraging and deserves deeper investigations with further preclinical and clinical studies. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2228-2240, 2017.

Past and present of interposition arthroplasties for joint repair with special tribute to the contribution by Vittorio Putti.

Several techniques have been proposed to restore the compromised function of a joint. These include the arthroplasty by placing various tissues or materials between the articular surfaces. An important contribution to the diffusion of arthroplasty techniques was made by Vittorio Putti, head of the Rizzoli Orthopedic Institute in Bologna from 1912 to 1940. Interposition arthroplasty is still used for some non-weight-bearing joints, such as wrist and elbow, and gives good results. This type of surgery has been further developed by the improvement in biomaterials, biomechanical studies and the regenerative medicine. This paper describes the development starting from a historical survey particularly focused on Putti's contribution and ending with the state of the art of regenerative medicine in the treatment of joint diseases. Level of evidence V.

Novel nanostructured scaffold for osteochondral regeneration: pilot study in horses.

The present in vivo preliminary experiment is aimed at testing mechanical and biological behaviour of a new nano-structured composite multilayer biomimetic scaffold for the treatment of chondral and osteochondral defects. The three-dimensional biomimetic scaffold (Fin-Ceramica Faenza S.p.A., Faenza-Italy) was obtained by nucleating collagen fibrils with hydroxyapatite nanoparticles, in two configurations, bi- and tri-layered, to reproduce, respectively, chondral and osteochondral anatomy. Chondral defects (lateral condyle) and deep osteochondral defects (medial condyle) were made in the distal epiphysis of the third metacarpal bone of both forelimbs of two adult horses and treated respectively with the chondral and osteochondral grafts. Both animals were euthanised six months follow up. The images obtained at the second look arthroscopy evaluation, performed two months after surgery, demonstrated good filling of the chondral and osteo-chondral defects without any inflammatory reaction around and inside the lesions. At the histological analysis the growth of trabecular bone in the osteochondral lesion was evident. Only in one case, the whole thickness of the osteochondral lesion was filled by fibrocartilaginous tissue. The formation of a tidemark line was evident at the interface with the newly formed bone. Newly formed fibrocartilaginous tissue was present in the area of the chondral defect. Initial alignment of the collagen fibres was recognisable with polarised light in both groups. The results of the present pilot study showed that this novel osteochondral and chondral scaffold may act as a suitable matrix to facilitate orderly regeneration of bone and hyaline-like cartilage.

In vitro culture of mesenchymal cells onto nanocrystalline hydroxyapatite-coated Ti13Nb13Zr alloy.

In this study we coated a new biocompatible, nanostructured titanium alloy, Ti13Nb13Zr, with a thin layer of hydroxyapatite nanocrystals and we investigated the response of human bone-marrow-derived mesenchymal cells. The coating was realized using a slightly supersaturated CaP solution, which provokes a fast deposition of nanocrystalline hydroxyapatite. A thin layer of deposition is appreciable on the etched Ti13Nb13Zr substrates after just 1.5 h soaking in the CaP solution, and it reaches a thickness of 1-2 mum after 3 h soaking. The coating seems thinner than that deposited on Ti6Al4V, which was examined for comparison, likely because of the different roughness profiles of the two etched alloys, and it is constituted of elongated HA nanocrystals, with a mean length of about 100 nm. Mesenchymal stem cells were seeded onto coated and uncoated Ti alloys and cultured for up to 35 days. Cell morphology, proliferation and differentiation were evaluated. The cells display good adhesion and proliferation on the uncoated substrates, whereas the presence of hydroxyapatite coating slightly reduces cell proliferation and induces differentiation of MSCs towards a phenotypic osteoblastic lineage, in agreement with the increase of the expression of osteopontin, osteonectin and collagen type I, evaluated by means of rt-PCR. Type I collagen expression is higher in Ti13Nb13Zr MSC culture compared to Ti6Al4V, standing for a more efficient extracellular matrix deposition.

Bioabsorbable scaffold for in situ bone regeneration.

A non-porous poly-DL-lactide tubular chamber filled by demineralised bone matrix (DBM) and bone marrow stromal cells (BMSC) in combination, was evaluated as a scaffold for guided bone regeneration (GBR) in an experimental model using the rabbit radius. The tubular chamber had an internal diameter of 4.7 mm, a wall thickness of 0.4 mm and a length of 18 mm. Autologous BMSC were obtained, under general anaesthesia from rabbit iliac crest and isolated by centrifugation technique. Allogenic DBM was obtained from cortico-cancellous bone of rabbits. In general anaesthesia, a 10-mm defect was bilaterally created in the radii of 10 rabbits. On the right side (experimental side) the defect was bridged with the chamber filled with both BMSC and DBM. On the left side (control side) the defect was treated by positioning DBM and BMSC between the two stumps. At an experimental time of 4 months histology and histomorphometry demonstrated that the presence of a tubular chamber significantly improved bone regrowth in the defect The mean thickness of newly-formed bone inside the chamber was about 56.7+/-3.74% of the normal radial cortex, in comparison with 46.7+/-10.7% when DBM and BMSC without the chamber were placed in the defect, P<0.05). These results confirmed the effectiveness of the chamber as a container for factors promoting bone regeneration.

In vivo study on the healing of bone defects treated with bone marrow stromal cells, platelet-rich plasma, and freeze-dried bone allografts, alone and in combination.

The repair of confined trabecular bone defects in rabbits treated by autologous bone marrow stromal cells (BMSC), platelet-rich plasma (PRP), freeze-dried bone allografts (FDBA) alone and in combination (BMSC + PRP; FDBA + BMSC; FDBA + PRP; FDBA + PRP + BMSC) was compared. A critical size defect was created in the distal part of the femurs of 48 adult rabbits. Histology and histomorphometry were used in the evaluation of healing at 2, 4, and 12 weeks after surgery. The healing rate (%) was calculated by measuring the residual bone defect area. Architecture of the newly formed bone was compared with that of bone at the same distal femur area of healthy rabbits. The defect healing rate was higher in PRP + BMSC, FDBA + PRP, FDBA + BMSC, and FDBA + PRP + BMSC treatments, while lower values were achieved with PRP treatment at all experimental times. The highest bone-healing rate at 2 weeks was achieved with FDBA + PRP + BMSC treatment, which resulted significantly different from PRP (p < 0.05) and BMSC (p < 0.05) treatments. At 4 weeks, the bone-healing rate increased except for PRP treatment. Finally, the bone-healing rate of FDBA + PRP, FDBA + BMSC, and FDBA + PRP + BMSC was significantly higher than that of PRP at 12 weeks (p < 0.05). At 12 weeks, significant differences still existed between PRP, BMSC, and FDBA groups and normal bone (p < 0.05). These results showed that the combination of FDBA, BMSC and PRP permitted an acceleration in bone healing and bone remodeling processes.

Prosthetic devices shaped as tubular chambers for the treatment of large diaphyseal defects by guided bone regeneration.

Guided tissue regeneration is based on the hypothesis that the different tissues have unequal abilities to penetrate a wounded area during the healing process. The use of a device acting as a chamber allows the growth of a particular tissue and prevents the ingrowth of other tissues which impair the healing process. At the same time the chamber protects and maintains in situ the intrinsic growth factors so that they may perform their specific activity. Guided tissue regeneration currently plays a well-recognized role mostly in dentistry and peripheral nerve surgery but interesting perspectives have also opened up in orthopedics. Considering the possibility of using guided bone regeneration in the repair of diaphyseal bone defects, this updated survey highlights some critical points and pathways related to the state-of-the-art of this promising procedure, focusing particularly on the properties of the material to make the tubular chamber, the use of osteopromotive factors and the most appropriate animal model to be used for the experimental evaluation.

The healing of confined critical size cancellous defects in the presence of silk fibroin hydrogel.

In vitro and in vivo behaviour of an injectable silk fibroin (SF) hydrogel was studied through osteoblast cultures and after implantation in critical-size defects of rabbit distal femurs. A commercial synthetic poly(D,L lactide-glycolide) copolymer was used as control material. In vitro biocompatibility was evaluated by measuring LDH release, cell proliferation (WST1), differentiation (ALP, OC), and synthetic activity (collagen I, TGF ss1, IL-6). Bone defect healing rate and quality of the newly formed bone inside the defects were determined in vivo by measuring trabecular bone volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), mineral apposition rate (MAR) and bone formation rate (BFR/B.Pm). In vitro tests indicated that both materials significantly increased cell proliferation in comparison with the negative control. A significant increase in the TGF-beta1 level was found for SF hydrogel in comparison with the control material and negative control. Both materials promoted bone healing when used to fill critical size defects in rabbit femurs. The new-formed bone of the SF hydrogel treated defects showed significantly higher BV/TV, Tb.Th, MAR and BFR/B.Pm and lower Tb.Sp values in comparison with the control gel. At 12 weeks the re-grown bone of the SF hydrogel-treated defects appeared more similar to normal bone than that of the control synthetic polymeric material-treated defects, except for the Tb.N value that differed significantly from that of normal bone (p<0.05). MAR and BFR/B.Pm presented significantly (p<0.05) higher values for SF hydrogel-treated defects in comparison with controls treated with a synthetic polymeric material, confirming that SF hydrogel accelerated remodelling processes.

Poly(2-hydroxyethyl methacrylate) biomimetic coating to improve osseointegration of a PMMA/HA/glass composite implant: in vivo mechanical and histomorphometric assessments.

Bone implants must simultaneously satisfy many requirements, even though the surface properties remain a crucial aspect in osseointegration success. Since a single material with a uniform structure cannot satisfy all of these requirements, composite materials specifically designed for orthopedic or dental implant application should be envisaged. Two poly(methylmethacrylate)/hydroxyapatite composites reinforced by E-glass fibres, uncoated (PMMA/HA/Glass) and poly(2-hydroxyethyl methacrylate) (PMMA/HA/Glass+pHEMA) coated by the biomimetic method, were mechanically (push-out test) and histomorphometrically (Affinity Index, AI) investigated in an in vivo rabbit model. Cylindrical implants (diameter 2 mm x 5 mm length) were inserted into rabbit femoral cortical (mid-diaphysis) and cancellous (distal epiphysis) bone, under general anesthesia. The highest values of push-out force and ultimate shear strength were observed for the PMMA/HA/Glass at 12 weeks, which significantly (p < 0.001) differed from those of PMMA/HA/Glass+pHEMA at the same experimental time and from those of PMMA/HA/Glass at 4 weeks. At both experimental times, significantly (p < 0.0005) lower values of AI were observed in the PMMA/HA/Glass+pHEMA versus PMMA/HA/Glass (distal femoral epiphysis: 4 weeks = 33%; 12 weeks = 19%; femoral diaphysis: 4 weeks = 15%; 12 weeks = 11%). The good mechanical and histomorphometric results obtained with PMMA/HA/Glass should be followed by further evaluation of bone remodeling processes and mechanical strength around loaded PMMA/HA/Glass implants at longer experimental times. Finally, the biomimetic method applied to pHEMA needs to be further investigated in order to improve the positive effect of SBF on pHEMA and to enhance the coating adhesion.

A new austenitic stainless steel with negligible nickel content: an in vitro and in vivo comparative investigation.

New nickel (Ni)-reduced stainless-steel metals have recently been developed to avoid sensitivity to Ni. In the present study, an austenitic Ni-reduced SSt named P558 (P558, Böhler, Milan, Italy) was studied in vitro on primary osteoblasts and in vivo after bone implantation in the sheep tibia, and was compared to ISO 5832-9 SSt (SSt) and Ti6Al4V. Cells were cultured directly on P558 and Ti6Al4V. Cells cultured on polystyrene were used as controls. Osteoblast proliferation, viability and synthetic activity were evaluated at 72 h by assaying WST1, alkaline phosphatase activity (ALP), nitric oxide, pro-collagen I (PICP), osteocalcin (OC), transforming growth factor-beta1 (TGFbeta-1) and interleukin-6 (IL-6) after 1.25(OH)2D3 stimulation. Under general anaesthesia, four sheep were submitted for bilateral tibial implantation of P558, SSt and Ti6Al4V rods. In vitro results demonstrated that the effect of P558 on osteoblast viability, PICP, TGF beta-1, tumor necrosis factor-alpha production did not significantly differ from that exerted by Ti6Al4V and controls. Furthermore, P558 enhanced osteoblast differentiation, as confirmed by ALP and OC levels, and reduced IL-6 production. At 26 weeks, the bone-to-implant contact was higher in P558 than in SSt (28%, p<0.005) and Ti6Al4V (4%, p<0.05), and was higher in Ti6Al4V than in SSt (22%, p<0.005). The tested materials did not affect bone microhardness in pre-existing host bone as evidenced by the measurements taken at 1000 microm from the bone-biomaterial interface (F=1.89, ns). At the bone-biomaterial interface the lowest HV value was found for SSt, whereas no differences in HV were observed between materials (F=1.55, ns). The current findings demonstrate P558 biocompatibility both in vitro and in vivo, and osteointegration processes are shown to be significantly improved by P558 as compared to the other materials tested.

In vitro behaviour of osteoblasts cultured on orthopaedic biomaterials with different surface roughness, uncoated and fluorohydroxyapatite-coated, relative to the in vivo osteointegration rate.

The effects of two surfaces with different roughness (Low Roughness, LR: Ra: 5.6-5.9 microm; High Roughness, HR: Ra: 21.5-22.5 microm), uncoated and fluorohydroxyapatite(FHA)-coated, were investigated in MG-63 osteoblasts. At 72 hours, cells proliferated on biomaterials more slowly than in the control group (p < 0.0001), the proliferation rate was higher on FHA-coated LR than uncoated HR (p = 0.037). Collagen-I production was positively affected by the LR surface (p = 0.001) as compared to controls, while it was significantly lower (p = 0.0001) in the HR surfaces. Compared to controls, LR and HR surfaces led to enhanced production of TGF-beta1, further improved by FHA (FHA-coated LR: p = 0.007; FHA-coated HR p < 0.0001 respectively). ALP, OC, IL-6 and TNF-alpha levels were not significantly different from the controls. Results suggest that collagen-I production could be useful in predicting the in vivo osteointegration rate of biocompatible biomaterials observed in previous studies.

Biomechanical and histomorphometric investigations on two morphologically differing titanium surfaces with and without fluorohydroxyapatite coating: an experimental study in sheep tibiae.

The influence of fluorohydroxyapatite (FHA) coating and surface roughness of Ti6Al4V implants on bone response was investigated. Uncoated and FHA-coated screws with lower (LR and LR+FHA; Ra: 5.7+/-0.2 microm) and higher (HR and HR+FHA; Ra: 21.8+/-0.9 microm) surface roughness, were inserted into the diaphyses of 8 sheep tibiae. Twelve weeks after implantation, extraction torque and bone-to-implant contact were evaluated. The smoothest surfaces showed an improved extraction torque and significant differences were observed between LR and HR (-24.6%, p<0.0005), LR and HR+FHA (-30.7%, p<0.0005), LR+FHA and HR (-17.4%, p<0.005), and LR+FHA and HR+FHA (-24.0%, p<0.005). The bone-to-implant contact data paralleled the biomechanical data: the smoother the surface, the greater the bone-to-implant contact. Significant (p<0.0005) decreases in bone-to-implant contact were observed between LR+FHA and HR (-24.2%), and between LR+FHA and HR+FHA (-29.2%). The current findings suggest that LR surfaces significantly improve the osteointegration rate of implanted cortical screws independently of the FHA coating.

X-ray micro-diffraction analysis of reconstructed bone at Zr prosthetic surface with sub-micrometre spatial resolution.

The purpose of the present investigation is to demonstrate the power of the x-ray micro-diffraction technique in biological studies. In particular the reported experiment concerns the study of the interface between a Zr prosthetic device implanted in a rat femur and the newly-formed bone, with a spatial resolution of 0.5 microm. The obtained results give interesting information on the Zr deformation and on the crystallographic phase, the grain size and the orientation of the new bone. Moreover the study reveals a marked difference in the structure of the reconstructed bone with respect to the native bone, which cannot be appreciated with other techniques.

Osteogenesis of large segmental radius defects enhanced by basic fibroblast growth factor activated bone marrow stromal cells grown on non-woven hyaluronic acid-based polymer scaffold.

Osteogenesis of large segmental radius defects in a rat model was studied by implanting a biodegradable non-woven hyaluronic acid-based polymer scaffold (Hyaff 11) alone or in combination with bone marrow stromal cells (BMSCs). These cells had been previously grown in vitro in mineralising medium either supplemented with basic fibroblast growth factor (bFGF) or unsupplemented. The healing of bone defects was evaluated at 40, 80, 160 and 200 days and the repair process investigated by radiographic, histomorphometric (assessment of new bone growth and lamellar bone) and histological analyses (toluidine blue and von Kossa staining). Mineralisation of bone defects occurred in the presence of the Hyaff 11 scaffold alone or when combined with BMSCs grown with or without bFGF, but each process had a different timing. In particular, bFGF significantly induced mineralisation from day 40, whereas 160 days were necessary for direct evidence that a similar process was developing under the other two conditions tested (scaffold alone or with BMSCs). Radiographic score, new bone growth and lamellar bone percentage were highly correlated. The present outcomes were further confirmed by toluidine blue and von Kossa staining. According to these in vivo findings, the Hyaff 11 scaffold is an appropriate carrier vehicle for the repair of bone defects; additionally, it can significantly accelerate bone mineralisation in combination with BMSCs and bFGF.

Tibial implants: biomechanical and histomorphometric studies of hydroxyapatite-coated and uncoated stainless steel and titanium screws in long-term ovariectomized sheep.

This study was designed to evaluate osteointegration of HA-coated and uncoated titanium and stainless steel screws in the cortical bone of long-term (24 months) ovariectomized sheep (OVX group), in comparison with Sham-aged sheep (control group). The screws were tested biomechanically (extraction torque) and histomorphometrically (affinity index: Al) 12 weeks after their implantation in tibial diaphyses. Tibial cortical bone parameters showed significant differences between the groups, showing a reduction of the selected parameters in the OVX group. ANOVA showed significant effects for both material and ovariectomy factors on obtained extraction torque (material: F=159.26, p < 0.0005; ovariectomy: F=20.04, p < 0.0005) and Al data (material: F=8.04, p < 0.001; ovariectomy: F=7, 17, p < 0.05). In both groups the extraction torque for coated screws of both materials was significantly higher than for uncoated screws, and uncoated titanium had a better extraction torque than uncoated stainless steel. In the OVX group, the HA-coated stainless steel and titanium Al data were significantly higher than uncoated Al data. In conclusion, the biomechanical and histomorphological results obtained suggest employing HA-coated screws in the presence of osteopenic cortical bone.

Laser technology in orthopedics: preliminary study on low power laser therapy to improve the bone-biomaterial interface.

Low Power Laser (LPL) seems to enhance the healing of bone defects and fractures. The effect of LPL in other orthopedic areas such as osteointegration of implanted prosthetic bone devices is still unclear. In the present study, 12 rabbits were used to evaluate whether Ga-Al-As (780 nm) LPL stimulation has positive effects on osteointegration. Hydroxyapatite (HA) cylindrical nails were drilled into both distal femurs of rabbits. From postoperative day 1 and for 5 consecutive days, the left femura of all rabbits were given LPL treatment (Laser Group-LG) with the following parameters: 300 Joule/cm2, 1 Watt, 300 Hertz, pulsating emission, 10 minutes. The right femura were sham-treated (Control Group-CG). At 4 and 8 weeks after implantation, histologic and histomorphometric investigations evaluated bone-biomaterial-contact. Histomorphometry showed a higher degree of osteointegration at the HA-bone interface in the LG Group at 4 (p < 0.0005) and 8 weeks (p < 0.001). These preliminary positive results seem to support the hypothesis that LPL treatment can be considered a good tool to enhance the bone-implant interface in orthopedic surgery.

Guided regeneration with resorbable conduits in experimental peripheral nerve injuries.

Guided tissue regeneration is a new approach in the reconstructive surgery of peripheral nerves. Artificial conduits can be constructed from biodegradable polymers. Lactic/caproic acid copolymers and polyphospazenes are biocompatible materials with a slow resorption rate. Conduits made from either poly-[1-lactide-co-6-caprolatone] or poly-[bis-(ethylalanate)-phosphazene] were assessed for use as guides for nerve regeneration in experimental animals. Under general anesthesia and by using a microsurgery technique both sciatic nerves were exposed in 2 groups of 9 Wistar rats. On the right side, a 10 mm segment of the nerve was removed, and the defect was then repaired using a conduit. On the left side, the same defect was bridged using as an autograft the nerve segment, which had been removed from the right sciatic nerve. Histological and electron microscopy investigations were performed after 30, 90 and 180 days and showed the gradual degradation of both types of conduits without any evidence of local toxicity. The regeneration of the nerve fibers in the lumen was not significantly different from that shown by the autologous grafts. Likewise, no differences were found at 180 days in the functional recovery of the nerve (evoked muscle action potential). Both conduits were found to be effective for guided nerve regeneration. Poly-[1-lactide-co-6-caprolactone] tubes were easier to insert, while polyphosphazene conduits allowed the use of neurite-promoting factors.