Flexor tendon healing within the tendon sheath using bioabsorbable poly-L/D-lactide 96/4 suture. A histological in vivo study with rabbits.

The bioabsorbable poly-L/D-lactide (PLDLA) 96/4 suture has good biomechanical and knot properties, and sufficient tensile strength half-life for flexor tendon repair. In the present study, the biocompatibility of PLDLA suture was compared with that of coated braided polyester suture in the rabbit flexor digitorum profundus tendon repaired within the tendon sheath. Postoperative unrestricted active mobilization was allowed. The tendons were studied histologically after 1-, 3-, 6-, 12-, 26-, and 52-week follow-ups. No differences were found in the biocompatibility between the suture materials, with only scattered multinuclear giant cells near the sutures in both groups from 6 weeks onwards. At 52 weeks, most of the PLDLA material was absorbed and the histological structure of the tendon appeared normal, whereas in the polyester repairs the suture knots filled the repair site, causing bulking of the tendon surface, and the collagen alignment appeared disoriented. The results suggest that the PLDLA 96/4 is a suitable suture material for flexor tendon repair.

The effect of pH on the degradation of biodegradable poly(L-lactide-co-glycolide) 80/20 urethral stent material in vitro.

PURPOSE: To investigate in vitro whether pH ranging between 6 and 9 has an effect on the degradation of stent fibers made of poly(l-lactide-co-glycolide) (PLGA) 80/20. MATERIALS AND METHODS: The fibers were divided into three groups and immersed in sodium phosphate-buffered saline (Na-PBS) solution with three different pH values: 6, 7.4, and 9. The mechanical and thermal properties were studied, and scanning electron microscopy (SEM) images were taken at specific time points of hydrolysis. RESULTS: The tensile testing showed that the strength of the fibers decreased through hydrolysis and was lost at 8 weeks in all groups. The T(m) and T(g) of the PLGA fibers did not indicate any significant differences between the different groups. In SEM images taken at 4 weeks, there were no significant differences between the fibers immersed in Na-PBS solutions of different pH values. However, at 8 weeks the surface of the fiber immersed in saline with a pH of 6 seemed coarser than that of those immersed in neutral (pH 7.4) or alkaline (pH 9) Na-PBS. CONCLUSION: The studied pH values did not influence the degradation behavior of the PLGA 80/20 fibers. Therefore, rabbits can be used as model animals for human biodegradable urological devices even though the pH of their urine is different.

Bioabsorbable poly-L/D-lactide (PLDLA) 96/4 triple-stranded bound suture in the modified Kessler repair: an ex vivo static and cyclic tensile testing study in a porcine extensor tendon model.

Previously the biomechanical properties of the bioabsorbable poly-L: /D: -lactide (PLDLA) 96/4 suture were found suitable for flexor tendon repair. In this study, three PLDLA suture strands were bound together parallel to each other side-by-side to form a triple-stranded bound suture and the modified Kessler tendon repair was performed. The biomechanical properties of the PLDLA repair in porcine extensor tendons ex vivo were investigated with static and cyclic tensile testing. In both biomechanical tests, the strength of the PLDLA repair achieved the estimated forces needed to withstand active mobilization.

Pull-out strength of multifunctional bioabsorbable ciprofloxacin-releasing polylactide-polyglycolide 80/20 tacks: an experimental study allograft cranial bone.

In this study, the pull-out forces of recently developed multifunctional bioabsorbable self-reinforced ciprofloxacin-releasing polylactide/polyglycolide (SR-PLGA+AB) 80/20 tacks were compared with plain SR-PLGA 80/20 tacks in human cadaver parietal bones. Pieces of parietal bone (approximately 6 x 20 cm) were harvested from 5 human cadavers (all were male, 29-77 years old). Fifty plain SR-PLGA tacks (diameter, 2.0 mm; length, 6.0 mm) and 50 ciprofloxacin-releasing SR-PLGA tacks of similar dimensions were applied to drill holes using a special tack shooter without tapping the drill holes. The force needed to pull the tacks from human parietal cadaver bones was measured using a universal tensile-testing machine, by tack pull-out speed of 10 mm/min. Means and SDs were calculated and analyzed using Student's t-test (SPSS version 10.0 for Windows). The pull-out forces of the ciprofloxacin-releasing and plain tacks were 147.0 +/- 5.94 and 141.4 +/- 8.97 N respectively (P = 0.14, statistically insignificant difference between the 2 groups). The cause of failure in all cases was barb breakage. Ciprofloxacin-releasing SR-PLGA 80/20 tacks seem to have a similar holding power to cranial bone as plain SR-PLGA (80/20) tacks but have additional advantage of ciprofloxacin release.

Fiber-reinforced bioactive and bioabsorbable hybrid composites.

Bioabsorbable polymeric bone fracture fixation devices have been developed and used clinically in recent decades to replace metallic implants. An advantage of bioabsorbable polymeric devices is that these materials degrade in the body and the degradation products exit via metabolic routes. Additionally, the strength properties of the bioabsorbable polymeric devices decrease as the device degrades, which promotes bone regeneration (according to Wolff's law) as the remodeling bone tissue is progressively loaded. The most extensively studied bioabsorbable polymers are poly-alpha-hydroxy acids. The major limitation of the first generation of bioabsorbable materials and devices was their relatively low mechanical properties and brittle behavior. Therefore, several reinforcing techniques have been used to improve the mechanical properties. These include polymer chain orientation techniques and the use of fiber reinforcements. The latest innovation for bioactive and fiber-reinforced bioabsorbable composites is to use both bioactive and bioresorbable ceramic and bioabsorbable polymeric fiber reinforcement in the same composite structure. This solution of using bioactive and fiber-reinforced bioabsorbable hybrid composites is examined in this study.

A new biodegradable braided self-expandable PLGA prostatic stent: an experimental study in the rabbit.

PURPOSE: The biodegradable PLGA (a copolymer of L-lactide and glycolide) urethral stent with a spiral configuration has been used clinically for the prevention of postoperative urinary retention after different types of thermal therapy for benign prostatic hyperplasia. A new braiding pattern for this stent has recently been developed by our group. The aim here was to investigate the in situ degradation and biocompatibility of the new braided stent in the rabbit urethra. MATERIALS AND METHODS: PLGA stents with a one-over-one braiding pattern and steel stents served as controls that were inserted into the posterior urethras of 24 male rabbits using a special delivery instrument. The animals were sacrificed after 1 week, 1 month, 2 months, or 4 months, and light microscopy and histologic analyses were performed. RESULTS: The delivery instrument worked well and cystoscopy was not needed in the insertion process. The braided PLGA stents degraded smoothly in 1 to 2 months. The metallic stents induced more epithelial hyperplasia and epithelial changes than the biodegradable stents at all time points analyzed. These differences increased during follow-up. CONCLUSION: The degradation process was well controlled and the biodegradable stents were more biocompatible than the metallic stents. The new stent can be inserted into the posterior urethra without cystoscopic aid.

Sustained release of ciprofloxacin from an osteoconductive poly(DL)-lactide implant.

BACKGROUND AND PURPOSE: Antibiotic-releasing bioresorbable implants are used for local treatment of bone infections, but most drug delivery systems release antibiotic for too short a time. METHODS: We used pellets (0.9 x 1.0 mm) made of bioabsorbable poly(DL) lactic acid matrix, ciprofloxacin (7.3 +/- 0.4 wt%), and bioactive glass microspheres of 90-125 microm (29.3 +/- 0.2 wt%). The ciprofloxacin release and antibacterial activity was measured in elution tests in vitro and local tissue concentrations were measured in rabbits. RESULTS: In elution tests in vitro, the therapeutic level (> 2 microg/mL) of ciprofloxacin was achieved within 6 h of the start of the test, and it was maintained for up to 300 days. The antibacterial activity of the antibiotic released from sterilized composites was similar to that of the unprocessed ciprofloxacin. In vivo measurements showed high local tissue concentrations (16-86 micrg/g of bone tissue) for 3 months. Compared to previous experiments on two-component polymeric matrices (PLGA or PDLLA) with ciprofloxacin alone, adding bioactive glass microspheres into the composite resulted in morphological changes that facilitated fluid intrusion into the microstructure and quickened ciprofloxacin release. INTERPRETATION: This type of composition of implant may fulfill the requirements of bone infection therapy, for sustained local release of the selected antibiotic over several months.

Long-term bone tissue reaction to polyethylene oxide/polybutylene terephthalate copolymer (Polyactive) in metacarpophalangeal joint reconstruction.

The poly-L/D-lactide 96/4 joint scaffolds are used to engineer fibrous tissue joints in situ for the reconstruction of metacarpophalangeal joints. In this experimental study, a supplementary elastomeric stem made of Polyactive 1000PEO70PBT30 (a segmented block copolymer of polyethylene oxide and polybutylene terephtalate with 70/30 PEO/PBT ratio) was used to anchor the joint scaffold in the arthroplasty space. Eleven resected fifth metacarpophalangeal joints of minipig were reconstructed and evaluated radiologically and histologically for 3 years. Plain joint scaffold and Swanson silicone implant arthroplasties (11 of each) in metacarpophalangeal joints of minipig served as controls. Altogether fore limbs of eighteen minipigs were operated for the study. Deleterious tissue reaction with dramatic signs of osteolysis and inflammatory foreign-body reaction was observed around the Polyactive stems. The mean maximum diameter of the osteolytic stem cavity was statistically wider when compared to the mean maximum diameter of Swanson implant group during the first postoperative year. Numerous osteoclasts were found at the margins of the osteolytic areas. No direct bone contact could be seen. At 1 year osteoblastic regeneration and formation of new trabecular bone followed. Finally the foreign-body reaction settled, but the adjoining bones were at this stage highly sclerotic and composed of coarse trabeculae. In contrary to previous in vivo studies suggesting biocompatibility, osteoconductivity and capability to bond to bone, Polyactive 1000PEO70PBT30 stem in this setting caused massive osteolytic lesions and foreign-body reactions.

The use of biodegradable scaffold as an alternative to silicone implant arthroplasty for small joint reconstruction: an experimental study in minipigs.

Biodegradable poly-L/D-lactide (P(L/D)LA) 96/4 joint scaffold arthroplasty is a recently clinically introduced concept in the reconstruction of small joints, however its histology and function in vivo is unknown. In this experimental study on 11 minipigs the fifth metacarpophalangeal joints were reconstructed using a P(L/D)LA 96/4 joint scaffold or Swanson silicone implant. They were evaluated until 3 years. The P(L/D)LA 96/4 joint scaffold formed a porous interposition spacer, which maintained the arthroplasty space and induced fibrous tissue in-growth in situ. No differences were found in the range of motion or arthroplasty space width between the study groups. The P(L/D)LA 96/4 joint scaffold was initially filled with vascular, loose connective tissue. Along with degradation of the scaffold, the in-grown connective tissue matured and condensed turning into dense fibrous connective tissue. After 3 years, the P(L/D)LA 96/4 joint scaffold had almost completely degraded and been replaced by dense fibrous connective tissue. These findings indicate that P(L/D)LA 96/4 joint scaffold arthroplasty leads to the formation of a functional fibrous joint. The avoidance of permanent foreign material makes the biodegradable joint scaffold an attractive alternative for small joint arthroplasty.

Fixation of experimental osteotomies with bioabsorbable SR-polylactide-polyglycolide (80/20) polymeric rods.

Self-reinforced polylactide-polyglycolide (80/20) composite rods, 2 mm in diameter and 36 mm in length, were implanted into the dorsal subcutaneous tissue of 20 rabbits. Osteotomies of the distal femur were fixed with these rods (2x15 mm) in the rabbits. The follow-up times varied from 3 to 104 weeks. After sacrifice, three-point bending and shear tests and molecular weight measurements were performed for subcutaneously placed rods. Radiological, histological, microradiographic, oxytetracycline-fluorescence, and histomorphometrical studies of the osteotomized and intact control femora were performed. After 6 weeks the mechanical properties had decreased significantly, but osteotomies had healed uneventfully. The present investigation showed that the mechanical strength and fixation properties of SR-Polylactide-glycolide (80/20) rods are suitable for fixation of cancellous bone osteotomies in rabbits provided that the operative technique is correct. The present article is the first report on the application of these rods for fixation of cancellous bone osteotomies.

Tissue biocompatibility of new biodegradable drug-eluting stent materials.

Drug-eluting stents are a recent innovation for endovascular and endourethral purposes. The aim of this study was to assess the biocompatibility of new biodegradable drug-eluting stent materials in vivo. Rods made of SR-PLDLA (self-reinforced poly-96L,4D: -lactic acid) covered with P(50L/50D)LA and rods made of 96L/4D SR-PLA and covered with P(50L/50D)LA including indomethacin 3.3 microg/mm(2)or dexamethasone 1.5 microg/mm(2), were inserted into the dorsal muscles of 20 rabbits serving as test animals. Rods made of silicone and organotin-positive polyvinylchloride were used as negative and positive controls. The animals were sacrificed after 1 week, 1 month, 2 months or 4 months. Histological changes attributable to the operative trauma were seen in all specimens at 1 week and 1 month. At 2 months both dexamethasone and indomethacin induced less fibrosis than the plain SR-PLDLA covered with P(50L/50D)LA without drug. At 4 months dexamethasone induced both chronic inflammatory changes and foreign body reaction, whereas the reactions in the indomethacin and drug-free plain SR-PLDLA groups were insignificant. The new biodegradable drug-eluting stent materials are highly biocompatible. Drug-eluting biodegradable stents may offer a promising new treatment modality for vascular and urethral diseases. However, further studies are needed to demonstrate their feasibility and efficacy.

The strength of the 6-strand modified Kessler repair performed with triple-stranded or triple-stranded bound suture in a porcine extensor tendon model: an ex vivo study.

PURPOSE: To investigate the biomechanic influence of triple-stranded sutures and the spatial arrangement of the strands on the strength of the 6-strand Pennington modified Kessler repair. METHODS: In the present ex vivo study of pig extensor tendons 2 techniques were used: (1) triple-stranded suture (3 suture strands in the same needle) and (2) triple-stranded bound suture (3 suture strands in the same needle that were bound together, parallel to each other, side by side). The repairs were subjected to static tensile testing. RESULTS: The 6-strand modified Kessler repair performed with triple-stranded bound suture reached significantly higher yield force, ultimate force, and both partial and total 1-, 2-, and 3-mm gap forces compared with the repairs performed with triple-stranded suture. The stiffness and strain values at the yield point and at the ultimate point did not differ significantly. CONCLUSIONS: This experimental study introduces a way to improve the strength of the tendon repair. The triple-stranded bound suture significantly increased both the gap resistance and ultimate force of the 6-strand modified Kessler repair. We assume the improvements are due to increased holding capacity of the locking loops. The triple-stranded bound suture is easy to use and avoids several problems associated with traditional multistrand repairs. Further studies are needed before clinical use can be considered.

Studies of P(L/D)LA 96/4 non-woven scaffolds and fibres; properties, wettability and cell spreading before and after intrusive treatment methods.

Poly(L/D)lactide 96/4 fibres with diameters of 50 and 80 microm were produced. The smaller diameter fibres were carded and needle punched to form a non-woven mat. Fibres and non-woven mats were hydrolysed for a period of 20 weeks. Fibres and pressed non-woven discs were treated with low-temperature oxygen plasma and alkaline KOH hydrolysis and ethanol washing was used as a reference treatment. The non-wovens lost 50% of their tear strength after 8 weeks in vitro while the fibres still retained 65% tensile strength after 20 weeks. Hydrolysation time in KOH, treatment time and power settings of the oxygen plasma were all directly proportional to the mechanical properties of the fibres. Increasing time (and power) resulted in lower tensile properties. Rapid wetting of the scaffolds was achieved by oxygen plasma, KOH hydrolysation and ethanol washing. Cell culturing using fibroblast cell line was carried out for the treated and non-treated non-woven scaffolds. In terms of adhesion and the spreading of the cells into the scaffold, best results after 3-day culturing were obtained for the oxygen plasma treated scaffolds.

Bioabsorbable screw fixation for the treatment of ankle fractures.

BACKGROUND: Self-reinforced poly(L/dL)lactide 70:30 (SR-PLA70) retains its strength in bone for 24 weeks, whereas self-reinforced poly-L-lactide (SR-PLLA) retains its strength for over 36 weeks. In this prospective randomized study, bioabsorbable 4.5-mm SR-PLA70 screws were compared with SR-PLLA screws in the treatment of displaced ankle fractures in adults. METHODS: Sixty-two patients with ankle fractures needing operative treatment were randomized into two groups. Comminuted fractures needing plating were excluded. In total 54 of 62 patients were followed up for 1 year by clinical evaluation, radiographs, and Olerud-Molander score. RESULTS: The study groups differed significantly only in the mean duration of sick leave (SR-PLA70, 60 days; SR-PLLA, 65 days; P = 0.02). At the 1-year follow-up, syndesmotic ossification was more common in the SR-PLA70 group (5 versus 1 patient, not significant). Radiologically, the screw channel had not disappeared in any of the patients by the 1-year follow-up. CONCLUSIONS: Both implant types proved to have good biocompatibility. SR-PLA70 and SR-PLLA screws are suitable in selected cases for the fixation of ankle fractures, but the mechanical stability of the fixation has to be carefully monitored perioperatively.

Drainage and antireflux characteristics of a biodegradable self-reinforced, self-expanding X-ray-positive poly-L,D-lactide spiral partial ureteral stent: an experimental study.

PURPOSE: To evaluate the drainage and antireflux characteristics of a new self-expandable self-reinforced poly-L,D-lactide partial ureteral stent (SR-PLA 96) in an experimental model. MATERIALS AND METHODS: Twelve dogs were used as experimental animals. A low-midline laparotomy and cystotomy were performed on all animals. In group A (six animals), 50-mm long SR-PLA 96 ureteral stents with a double-helical spiral design were inserted into both ureters, leaving the lower ends 2 cm above the ureterovesical junction. In group B (six animals), both ureters were stented with traditional pigtail stents (C-Flex) Double-J; Cook Urological), which were removed 8 weeks after surgery. Renal function and ureteral patency were evaluated by dynamic kidney imaging and urography examinations at 6 and 12 weeks postoperatively. The degrees of vesicoureteral reflux at two levels of the ureters and at the level of the renal pelvis were evaluated by nuclear voiding cystograms at 6 weeks. RESULTS: The partial SR-PLA 96 stent design showed more favorable antireflux properties that the Double-J stent design. The degree of vesicoureteral reflux, reflected in an increase of nuclear enhancement at 6 weeks, was lower in the distal (7.9% +/- 14.7% v 63.2% +/- 17.3%; P < 0.05) and middle (6.1% +/- 8.1% v. 45.5% +/- 19.5%; P = 0.15) levels of the ureters as well as at the level of the renal pelvis (-3.4% +/- 3.6% v 6.2% +/- 3.9%; P = 0.65) than in the Double-J-stented ureters. No significant differences in renal function or ureteral patency were observed at 12 weeks after the Double-J stents had been removed and the SR-PLA 96 stents had fragmented. CONCLUSION: A self-expandable, self-reinforced SR-PLA 96 partial ureteral stent showed more favorable antireflux properties than a Double-J stent.

Release of diclofenac sodium from polylactide-co-glycolide 80/20 rods.

Due to inflammatory reactions complicating bioabsorbable devices, the aim of this study was to develop and characterize bioabsorbable implants with anti-inflammatory drug releasing properties. Polylactide-co- glycolide (PLGA) 80/20 was compounded with diclofenac sodium (DS) to produce rods. Thermal properties were analyzed using differential scanning calorimetry (DSC). Inherent viscosity (eta(inh)) was measured to evaluate the drug effect on the extrude polymer. Drug release measurements were performed using UV-spectrophotometer. Five parallel samples from each type of rods were examined, first at 6 hour intervals, then on daily basis, and later twice a week. DS was released in 110 days from thinner rods and in 150 days from thicker rods. Drug release comprised a starting peak, slow release phase, then a high release phase, and a burst release phase. DSC analysis showed that DS containing rods had crystallinity in their structure. In conclusions, it is feasible to combine PLGA 80/20 and DS by using melt extrusion. Released DS concentrations reached local therapeutic levels, but the release profile was complex and therapeutic levels were not reached all the time.

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.

Poly-L/D-lactide (PLDLA) 96/4 fibrous implants: histological evaluation in the subcutis of experimental design.

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.

Self-reinforced ciprofloxacin-releasing polylactide-co-glycolide 80/20 inhibits attachment and biofilm formation by Staphylococcus epidermidis: an in vitro study.

We have observed the efficiency of antibiotic-releasing polylactide-co-glycolide (PLGA) 80/20 in preventing Staphylococcus epidermidis attachment and biofilm formation in vitro. The aim of the present study was to evaluate the effect of self-reinforced (SR) implants with enhanced antibiotic release on bacterial attachment and biofilm formation rates, and also on growth inhibition of Staphylococcus epidermidis. Cylindrical SR-PLGA+AB specimens (length 30 mm, diameter 3 mm) were examined by scanning electron microscopy (SEM) for attachment of S. epidermidis ATCC 35989 on biomaterial surface and formation of biofilm, after incubating with bacterial suspension of ca. 10 cfu/mL for 1, 3, 7, 14 and 21 days. SR-PLGA and SR-PLGA+AB implants were tested on agar plates by measuring the inhibition distance around implants. On the surface of SR-PLGA+AB, at days 1, 3, 7, 14 and 21, the percentage of areas with not a single bacteria attached, was 88.6%, 71.1%, 73.7%, 73.7%, and 68.4%, respectively. On the areas where bacteria were detected, the number of bacterial cells remained low during whole study period, and no significant increase by time was seen. There was no biofilm observed on 97-99% of the examined areas during the whole study period on SR-PLGA+AB. In agar plates, the SR-PLGA+AB showed inhibition of bacterial growth, with (mean) 53.2 mm diameter of inhibition area with peeled implants and 50.5 mm with non-peeled implants. There was no inhibition seen around implants without ciprofloxacin. Bioabsorbable ciprofloxacin-releasing self-reinforced PLGA (SR-PLGA+AB) was superior to plain SR-PLGA in preventing bacterial attachment, biofilm formation, and also the growth of Staphylococcus epidermidis.

In vitro and in vivo testing of bioabsorbable antibiotic containing bone filler for osteomyelitis treatment.

The use of local antibiotics from a biodegradable implant is appealing concept for treatment of chronic osteomyelitis. Our aim was to develop a new drug delivery system based on controlled ciprofloxacin release from poly(D/L-lactide). Cylindrical composite pellets (1.0 x 0.9 mm) were manufactured from bioabsorbable poly(D/L-lactide) matrix and ciprofloxacin (7.4 wt %). In vitro studies were carried out to delineate the release profile of the antibiotic and to verify its antimicrobial activity by means of MIC testing. A long-term study in rabbits was performed to validate the release of ciprofloxacin from the composite in vivo. Therapeutic level of ciprofloxacin (>2 microg/mL) was maintained between 60 and 300 days and the concentration remained below the potentially detrimental level of 20 microg/mL in vitro. The released ciprofloxacin had retained its antimicrobial properties against common pathogens. In an exploratory long-term in vivo study with three rabbits, ciprofloxacin could not be detected from the serum after moderate filling (160 mg) of the tibia (follow-up 168 days), whereas after high dosing (a total dose of 1,000 mg in both tibias) ciprofloxacin was found temporarily at low serum concentrations (14-34 ng/mL) during the follow-up of 300 days. The bone concentrations of ciprofloxacin could be measured in all samples at 168 and 300 days. The tested copolylactide matrix seems to be a promising option in selection of resorbable carriers for sustained release of antibiotics, but the composite needs modifications to promote ciprofloxacin release during the first 60 days of implantation.