Previously, ciprofloxacin-releasing polylactide/polyglycolide 80/20 (SR-PLGA) screws have proven to be biocompatible with sufficient strength. However, there has been no information about the local concentrations of ciprofloxacin in bone tissue after their implantation. To measure bone concentrations of ciprofloxacin, two screws were implanted in each rabbit, one on either side of the sagittal suture (n = 28 rabbits). Follow-up periods were 2, 4, 8, 16, 24, 52 and 78 weeks. From each rabbit, bone blocks containing one screw were retrieved and used to measure drug concentration. Ciprofloxacin concentration at 2 weeks follow-up was 4.4 ± 4.2 μg/g, 14.1 ± 2.7 μg/g at 4 weeks and 7.6 ± 4.5 μg/g at 8 weeks. Measured concentrations were very low at 16 weeks (mean 0.09 ± 0.04 μg/g) and 24 weeks (mean 0.04 ± 0.02 μg/g). Surprisingly, the concentration was higher again at 1 year (mean 1.3 ± 1.0 μg/g). At 1.5 years, concentration had decreased again (mean 0.8 ± 0.6 μg/g). The drug concentration in bone tissue was higher than minimal inhibitory concentration of ciprofloxacin (Staphylococcus aureus 0.1–1.0 μg/g) at 2, 4, and 8 weeks. Ciprofloxacin-releasing SR-PLGA 80/20 screws could be used clinically for osteofixation and infection treatment in cranial bone.

Transplantation of autologous fat as pedicle or transposition flaps has been a classical method in plastic surgery for tissue reconstruction. The injection of fat for soft tissue reconstruction is also an old innovation. This approach has some significant drawbacks such as resorption of the fat transplant. To regenerate additional and self-regenerating adipose tissue for reconstructive purposes, a thorough understanding of adipose tissue (mesodermal stem cells, adipoblasts, pre-adipocytes, mature, lipid-synthesizing, and lipid-storing white or brown adipocytes) on cellular and molecular levels is required. Several transcription factors that play a central role in the control of adipogenesis have been identified; Among these are the CCAAT/enhancer binding protein gene family and peroxisome proliferator-activated receptor-gamma. Hormones and growth factors, such as insulin and insulin-like growth factor (IGF), transfer external signals to differentiating adipocytes. In an attempt to improve the quality of tissue-engineered fat by culture-expanded adipocytes, various pre-adipocyte and stem cell culture conditions and expansion methods have been developed. In the presence of fetal calf serum, spontaneous differentiation of pre-adipocytes into fat cell clusters occurs to some degree. This in vitro differentiation can be enhanced by addition of inducing agents such as dexamethasone, isobutylmethylxantine, and insulin into the culture medium. Recent work has shown the multipotency of pre-adipocytes, which are fibroblast-like precursors of adipocytes. With use of specific culture conditions, human adipose tissue-derived stem cells can be induced to express markers of adipocyte, osteoblast, and myocyte cell lineages. The multipotent characteristics of adipose tissue-derived stem cells, as well as their abundance and accessibility in the human body, make them a potential cell source for tissue engineering applications.

Transplantation of autologous fat as pedicle or transposition flaps has been a classical method in plastic surgery for tissue reconstruction. The injection of fat for soft tissue reconstruction is also an old innovation. This approach has some significant drawbacks such as resorption of the fat transplant. To regenerate additional and self-regenerating adipose tissue for reconstructive purposes, a thorough understanding of adipose tissue (mesodermal stem cells, adipoblasts, pre-adipocytes, mature, lipid-synthesizing, and lipid-storing white or brown adipocytes) on cellular and molecular levels is required. Several transcription factors that play a central role in the control of adipogenesis have been identified. Among these are the CCAAT/enhancer binding protein gene family and peroxisome proliferator-activated receptor-gamma. Hormones and growth factors, such as insulin and insulin-like growth factor (IGF), transfer external signals to differentiating adipocytes. In an attempt to improve the quality of tissue-engineered fat by culture-expanded adipocytes, various pre-adipocyte and stem cell culture conditions and expansion methods have been developed. In the presence of fetal calf serum, spontaneous differentiation of pre-adipocytes into fat cell clusters occurs to some degree. This in vitro differentiation can be enhanced by addition of inducing agents such as dexamethasone, isobutylmethylxantine, and insulin into the culture medium. Recent work has shown the multipotency of pre-adipocytes, which are fibroblast-like precursors of adipocytes. With use of specific culture conditions, human adipose tissue-derived stem cells can be induced to express markers of adipocyte, osteoblast, and myocyte cell lineages. The multipotent characteristics of adipose tissue-derived stem cells, as well as their abundance and accessibility in the human body, make them a potential cell source for tissue engineering applications.

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 1½ 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.

Poly-L/D-lactide (PLDLA) 96/4 fibrous implants have been introduced to engineer functional fibrous constructions in situ. The current study was undertaken to evaluate the guidance of the fibrous tissue formation and the tissue reaction of porous PLDLA 96/4 scaffolds implanted in subcutaneous tissue. Three various PLDLA 96/4 knitted-mesh scaffolds (Loose, Ordinary, and Dense) were implanted subcutaneously in 32 rats, and followed-up from 3 days until 48 weeks postsurgery. Histological examination showed that PLDLA 96/4 scaffolds provided a structurally supporting element for 48 weeks. They were filled with fibrous tissue by 3 weeks. During the follow-up, loose connective tissue was organized into dense connective tissue with thick collagen bundles. At 48 weeks, no statistically significant difference was found in the amount of loose or dense connective tissue between the scaffold groups of various porosities, although the tendency for higher amounts of loose connective tissue was seen in the Loose type scaffolds. PLDLA filament diameters were 121 mum at 2 weeks, 119 mum at 24 weeks and 116 mum at 48 weeks (P = 0.03 between 2 and 48 weeks). Porous PLDLA scaffold induced fibrous tissue formation in situ. This can be exploited in engineering fibrous tissue constructs in vivo for tissue support or replacement purposes.

PURPOSE:To analyze histologically tissue reactions to bioabsorbable PLA96 in rabbit eyes. METHODS:Scleral buckling operations were carried out in 48 rabbits. Two materials were used: bioabsorbable PLA96 (polylactide 96/4; L/D molar ratio 96/4) and silicone sponge. One eye of each rabbit was operated on and the other eye served as a nonoperated control. After follow-up times of 1, 3, 5, and 12 months, the rabbits were killed and the eyes enucleated for histology. RESULTS:All rabbits recovered well. Histologically, tissue reactions were very localized; implant fragments were not seen within the sclera. The amounts of fibrous tissue and inflammatory cells (mainly macrophages) inside the implant area increased over time. One rabbit from the silicone group was killed 4 months postoperatively owing to refusal to eat. In the PLA96 group, acute or chronic infections occurred in four rabbits. The bioabsorbable implant was macroscopically easily detectable at 12 months postoperatively. CONCLUSIONS:The PLA96 material used for scleral buckling in rabbits showed good biocompatibility. The material did not undergo biodegradation during the follow-up period of 12 months. PLA96 implants were associated with thicker fibrous tissue encapsulation and more inflammatory cells compared with silicone sponge implants.

PURPOSE:To measure the amount and duration of indentation depth achieved with biodegradable poly-L/D-lactide 96/4 (PLA96) and silicone sponge implants. METHODS:Thirty rabbits underwent a scleral buckling procedure. A PLA96 buckling implant was used in 15 rabbits and a silicone sponge buckling implant was in 15 rabbits. A circumferential scleral buckling implant was sutured episclerally on the left eye of each rabbit, just temporal to the superior rectus muscle and 7 mm posterior to the limbus. Computed tomography was performed at 1 week, 3 months, and 5 months after surgery. RESULTS:The PLA96 buckling implant (implant diameter, 3-3.5 mm) used in this study created lower indentation than the silicone sponge implant (implant diameter, 4 mm). The indentation created by the PLA96 implant decreased over time compared with that created by the silicone implant. There were no complications related to either kind of implant. CONCLUSION:Both the silicone sponge implant and the PLA96 implant caused indentation that decreased in a comparable manner over the follow-up period (5 months).

A self-reinforced bioabsorbable poly-L-lactide/polyglycolide (SR-PLGA) 80/20 screw 2.0 mm in diameter was implanted transphyseally across the distal growth plate of the right femur in 24 immature rabbits. Radiologic evaluation revealed a mean shortening of 3.1 mm at 3 weeks, 11.1 mm at 6 weeks, 9.3 mm at 24 weeks, 9.0 mm at 48 weeks, and 12.6 mm at 72 weeks compared with the intact contralateral femur. In 13 control rabbits, drilling without screw placement did not cause any statistically significant femoral shortening. Therefore, the transphyseal SR-PLGA 80/20 screw caused growth retardation for 6 weeks postoperatively, after which the normal growth tendency was recovered until the growth plate was closed. The duration of temporary growth retardation correlated with that of strength retention of the SR-PLGA 80/20 copolymer. These findings suggest that SR-PLGA 80/20 screws can be applied in transphyseal bone fixation. The use of bioabsorbable screws for temporary epiphysiodesis seems attractive but requires further study.

Bioabsorbable osteofixation devices were developed to avoid problems associated with metals. Bioabsorbable devices are mostly made of the polymers polylactide, polyglycolide, and their copolymers [polyglycolide-co-polylactide and P(L/DL)LA]. Using the technique of self-reinforcement of bioabsorbable materials, it is possible to manufacture osteofixation devices with ultra high strength. Self-reinforced polyglycolide-co-polylactide 80/20 was selected to make devices (Biosorb PDX) for this study because of its favorable degradation characteristics. The aim of this study was to evaluate the efficacy of using self-reinforced polyglycolide-co-polylactide 80/20 (Biosorb) plates and screws in the fixation of osteotomies in craniomaxillofacial surgery. In a prospective study, 165 patients (161 children and 4 adults) were operated on in four European Union centers (Paris, Innsbruck, London, and Oulu) from May 1, 1998 to January 31, 2002. Indications included correction of dyssynostotic deformities (n = 159), reconstruction of bone defects after trauma (n = 2), tumor removal (n = 2), and treatment of encephalocele (n = 2). Plates used were 0.8, 1, or 1.2 mm thick, and screws had an outer (thread) diameter of 1.5 or 2 mm and a length of 4, 6, or 8 mm. Tacks had an outer diameter of 1.5 or 2 mm and a length of 4 or 6 mm. During surgery, the devices were easy to handle and apply and provided stable fixation apart from 2 cases. Postoperative complications occurred in 12 cases (7.3%), comprising infection (n = 6), bone resorption (n = 4), diabetes insipidus (n = 1), delayed skin wound healing/skin slough (n = 2), and liquorrhea (n = 1). Accordingly, self-reinforced polyglycolide-co-polylactide 80/20 (Biosorb) plates and screws can be used safely and with a favorable outcome in corrective cranioplasties, especially in infants and young children.

The aim of this study was to investigate the rate of disappearance of noradrenaline in arterial grafts after their transplanation. Arterial grafts were harvested from AO/Ks:OC strain rats. In each rat, a graft was harvested from the femoral artery and transplanted into the common carotid artery. A contralateral unoperated femoral artery served as control. High‐performance liquid chromatography (HPLC) with electrochemical detection was used to determine the noradrenaline content in grafts and controls. Immediately after grafting, the noradrenaline content was 76% of control value, at 6 h 130% of control value, and at 48 h 4% of control value. The drop in graft noradrenaline content (from 0–48 h) was statistically significant (P = 0.005). The difference between 0‐h, 12‐h, and 24‐h groups was statistically insignificant. Compared to control specimens, grafts contained less noradrenaline after 12 h, and it disappeared almost completely from femoral arterial grafts in rats within 48 h. © 2004 Wiley‐Liss, Inc.

Rat carotid bodies were studied electron microscopically after short-term severe hypovolaemia, which is known to induce a marked chemoreceptor activation in the carotid body. Altogether 84 nerve-endings in the hypovolaemic rats' carotid bodies and 91 nerve-endings in the control carotid bodies were investigated. An increased accumulation of the glomus cell granular vesicles near the synaptic specializations of the nerve-endings was observed after hypovolaemia. Moreover, a statistically significant increase in the contacts between the nerve-ending synaptic specializations and the glomus cell granular vesicles was observed after hypovolaemia. A suggestion was made that the glomus cells might act as modulating, probably inhibitory, interneurones, whose catecholamines are responsible for the inhibition.