Ali Gürlek

Manufacture of porous biodegradable polymer conduits by an extrusion process for guided tissue regeneration

We have fabricated porous, biodegradable tubular conduits for guided tissue regeneration using a combined solvent casting and extrusion technique. The biodegradable polymers used in this study were poly(DL-lactic-co-glycolic acid) (PLGA) and poly(L-lactic acid) (PLLA). A polymer/salt composite was first prepared by a solvent casting process. After drying, the composite was extruded to form a tubular construct. The salt particles in the construct were then leached out leaving a conduit with an open-pore structure. PLGA was studied as a model polymer to analyze the effects of salt weight fraction, salt particle size, and processing temperature on porosity and pore size of the extruded conduits. The porosity and pore size were found to increase with increasing salt weight fraction. Increasing the salt particle size increased the pore diameter but did not affect the porosity. High extrusion temperatures decreased the pore diameter without altering the porosity. Greater decrease in molecular weight was observed for conduits manufactured at higher temperatures. The mechanical properties of both PLGA and PLLA conduits were tested after degradation in vitro for up to 8 weeks. The modulus and failure strength of PLLA conduits were approximately 10 times higher than those of PLGA conduits. Failure strain was similar for both conduits. After degradation for 8 weeks, the molecular weights of the PLGA and PLLA conduits decreased to 38% and 43% of the initial values, respectively. However, both conduits maintained their shape and did not collapse. The PLGA also remained amorphous throughout the time course, while the crystallinity of PLLA increased from 5.2% to 11.5%. The potential of seeding the conduits with cells for transplantation or with biodegradable polymer microparticles for drug delivery was also tested with dyed microspheres. These porous tubular structures hold great promise for the regeneration of tissues which require tubular scaffolds such as peripheral nerve, long bone, intestine, or blood vessel.

In vivo evaluation of poly(l-lactic acid) porous conduits for peripheral nerve regeneration

The present study provides in vivo trials of poly(L-lactic acid) (PLLA) as a porous biodegradable nerve conduit using a 10 mm sciatic nerve defect model in rats. The PLLA conduits, fabricated by an extrusion technique, had an inner diameter of 1.6 mm, an outer diameter of 3.2 mm, and a length of 12 mm. They were highly porous with an interconnected pore structure (of 83.5% porosity and 12.1 microm mean pore size). The conduits were interposed into the right sciatic nerve defect of Sprague Dawley rats using microsurgical techniques; nerve isografts served as controls. Walking track analysis was performed after conduit placement monthly through 16 weeks. At the conclusion of 6 and 16 weeks, sections from the isograft/conduit and distal nerve were harvested for histomorphometric analysis. The right gastrocnemius muscle was also harvested and its weight was determined. All conduits remained intact without breakage. Moreover, no conduit elongated during the 16 weeks of placement. Walking track analysis and gastrocnemius muscle weight demonstrated increasing regeneration over the 16 weeks in both the conduit and isograft control groups, with control values significantly greater. The nerve fiber density in the distal sciatic nerve for the PLLA conduits (0.16+/-0.07) was similar to that for the control isografts (0.19+/-0.05) at 16 weeks. The number of axons/mm2 in the distal sciatic nerve for the PLLA conduits was lower than that for the isografts (13 800+/-2500 vs. 10700+/-4700) at 16 weeks. The results for PLLA were significantly improved over those for 75:25 poly(DL-lactic-co-glycolic acid) of a previous study and suggest that PLLA porous conduits may serve as a scaffold for peripheral nerve regeneration.

Ectopic bone formation by marrow stromal osteoblast transplantation using poly(DL-lactic-co-glycolic acid) foams implanted into the rat mesentery

Porous biodegradable poly(DL-lactic-co-glycolic acid) foams were seeded with rat marrow stromal cells and implanted into the rat mesentery to investigate in vivo bone formation at an ectopic site. Cells were seeded at a density of 6.83 x 10(5) cells/cm2 onto polymer foams having pore sizes ranging from either 150 to 300 to 710 microns and cultured for 7 days in vitro prior to implantation. The polymer/cell constructs were harvested after 1, 7, 28, or 49 days in vivo and processed for histology and gel permeation chromatography. Visual observation of hematoxylin and eosin-stained sections and von Kossa-stained sections revealed the formation of mineralized bonelike tissue in the constructs within 7 days postimplantation. Ingrowth of vascular tissue was also found adjacent to the islands of bone, supplying the necessary metabolic requirements to the newly formed tissue. Mineralization and bone tissue formation were investigated by histomorphometry. The average penetration depth of mineralized tissue in the construct ranged from 190 +/- 50 microns for foams with 500-710-microns pores to 370 +/- 160 microns for foams with 150-300-microns pores after 49 days in vivo. The mineralized bone volume per surface area and total bone volume per surface area had maximal values of 0.28 +/- 0.21 mm (500-710-microns pore size, day 28) and 0.038 +/- 0.024 mm (150-300-microns, day 28), respectively. As much as 11% of the foam volume penetrated by bone tissue was filled with mineralized tissue. No significant trends over time were observed for any of the measured values (penetration depth, bone volume/surface area, or percent mineralized bone volume). These results suggest the feasibility of bone formation by osteoblast transplantation in an orthotopic site where not only bone formation from transplanted cells but also ingrowth from adjacent bone may occur.

Functional results of dental restoration with osseointegrated implants after mandible reconstruction.

&NA; We reviewed the cases of 20 cancer patients (mean age 47.4 years) in whom osseointegrated implants were used for dental restoration after mandibular reconstruction between January of 1988 and December of 1994. Seventyone implants were placed into bone flaps (n = 60) or native mandible (n = 11), an average of 3.55 per patient (range, 2 to 5). Successful integration occurred in 91.5 percent (65 of 71); there were five early failures and one late failure, with no significant difference between the number lost in microvascular flaps (5 of 60) and native mandible (1 of 11) (as determined by Fishers exact test). Functional evaluation included assessments of diet, speech, and cosmesis. Based on our review, we concluded that (1) implants enhance dental restoration in selected patients, and (2) microvascular bone flaps, including the fibula and iliac crest, are well suited for dental implant restoration.

Drug-induced vasodilation in an in vitro and in vivo study: the effects of nicardipine, papaverine, and lidocaine on the rabbit carotid artery.

&NA; Extreme arterial vasoconstriction (vasospasm) is a common problem encountered in microvascular surgery. An ideal pharmacologic tool able to counteract ischemia during microsurgery should be easy to apply and exert its action both locally and distally in the microcirculation of the flap. We have compared in vitro and in vivo vascular properties of nicardipine, papaverine, and lidocaine in the rabbit carotid artery. In vitro, rings from the rabbit carotid artery (n = 7) were bathed in Krebs‐Ringers solution and stretched progressively to an optimal tension of 3.7 to 4.2 g. The specimens were contracted with norepinephrine (1 &mgr;M), and a cumulative dose response curve was established. In vivo, microvascular anastomoses were performed bilaterally in the rabbit carotid artery in 35 animals using 9‐0 nylon suture and standard microsurgical techniques. During and after the anastomoses, nicardipine (0.1, 0.01 mg topical, or 0.1 mg/hour IV), papaverine (30 mg/cc topical), and lidocaine (2% with and without epinephrine) were applied (blinded) at the anastomotic site in five rabbits each. Heparinized sodium chloride was used as topical irrigation for control and to clean the anastomosis. Blood flow changes were monitored continuously with the transonic Doppler for 30 minutes after the procedure. The systemic blood pressure was also monitored in a group of pilot experiments. A documented decrease in blood flow was noted in all animals after the microvascular anastomosis. Nicardipine and papaverine evoked a concentrationdependent relaxation to precontracted rings to norepinephrine. Nicardipine was greater than papaverine in inducing relaxation. Lidocaine demonstrated a biphasic response with low concentrations potentiating contraction. Systemic nicardipine and papaverine significantly increased the blood flow in the rabbit carotid artery. Topical application of nicardipine and lidocaine did not significantly alter the blood flow; however, the application of nicardipine demonstrates a trend toward increased flow. Lidocaine with epinephrine significantly decreased the blood flow. No drug was found to alter the blood pressure of the animals. Our results demonstrate that nicardipine and papaverine seem to be pharmacologic tools able to increase the blood flow in anastomotic arteries. In contrast, the use of 2% lidocaine as a spasmolytic agent should be re‐evaluated, since this substance may act as a partial agonist. (Plast. Reconstr. Surg. 100: 1475, 1997.)

Effects of Different Corticosteroids on Edema and Ecchymosis in Open Rhinoplasty

A double-blind, randomized trial with placebo control was planned to evaluate the effects of corticosteroids (betamethasone, dexamethasone, methylprednisolone) in approximately equivalent doses (8 mg dexamethasone/day), and to compare their effects with that of tenoxicam, an antiinflammatory drug, on both the edema and ecchymosis in open rhinoplasty with osteotomies. For this study, 40 patients were divided randomly into five groups of 8 patients each, which received, respectively, betamethasone (group 1), dexamethasone (group 2), methylprednisolone (group 3), tenoxicam (group 4), and placebo (group 5). Open rhinoplasty with osteotomies was performed by the same surgeon with the patient under general anesthesia. Drugs were administered just before the induction of anesthesia and continued for 3 days. Only acetaminophen was used to control postoperative analgesia. Digital photographs of each patient were taken on postoperative days 1, 3, and 7. Scoring was performed separately for eyelid swelling and ecchymosis by three observers independently using a graded scale from 0 to 4. No statistically significant differences existed among the five groups in terms of age, sex, duration of surgery, amount of bleeding, and intravenous fluid administration during the surgery. On postoperative days 1, 3, and 7, no differences in the levels of ecchymosis or edema among the steroid groups, the tenoxicam group, and the control groups were observed. In conclusion, the authors observed no significant differences among the different kinds of steroids administered in equivalent doses (8 mg dexamethasone/day). Steroids used in these doses were not effective in preventing or reducing edema and ecchymosis after open rhinoplasty with osteotomies. Tenoxicam also was not effective. No complications caused by the use of steroids were observed during the 6-month follow-up period.

Protective effect of melatonin on random pattern skin flap necrosis in pinealectomized rat

Abstract: Random pattern skin flaps are still widely used in plastic surgery. However, necrosis in the distal portion resulting from ischemia is a serious problem, increasing the cost of treatment and hospitalization. Free oxygen radicals and increased neutrophil accumulation play an important role in tissue injury and may lead to partial or complete flap necrosis. To enhance skin flap viability, a variety of pharmacological agents have been intensively investigated. The aim of this study is to test the effects of melatonin, the chief secretory product of the pineal gland and a highly effective antioxidant, on random pattern skin flap survival in rats. Herein, to investigate the physiological and pharmacological role of melatonin on dorsal skin flap survival. Pharmacological (0.4, 4 and 40 mg/kg) levels of melatonin were given intraperitoneally (i.p.). For this, pinealectomized (Px) and sham operated (non‐Px) rats were used. The effects of melatonin on levels of malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH) and the activities of glutathione peroxidase (GSH‐Px) and superoxide dismutase (SOD) were measured in the skin flap. The ratio of skin flap necrosis was compared among the experimental groups by using planimetry. MDA and NO levels were found to be higher in Px than non‐Px rats; while GSH levels and GSH‐Px, and SOD activities were reduced. Melatonin administration to Px rats reduced MDA and NO levels and increased GSH, GSH‐Px, SOD levels. Melatonin also reduced the ratio of flap necrosis determined by using planimetry and supported through the photography. In conclusion, these results show that both physiological and pharmacological concentrations of melatonin improve skin flap viability.

Aesthetic Reconstruction of Large Scalp Defects by Sequential Tissue Expansion Without Interval

Tissue expansion is indicated in the reconstruction of various scalp defects when there is inadequate adjacent tissue to allow either primary closure of the defect or repair with a local flap. It is the most important armamentarium for aesthetic hair-bearing scalp reconstruction in cases of congenital or required defects. This technique was used sequentially without interval to achieve scalp reconstruction for 12 patients with a defect ranging from 30% to 75% of the scalp (average, 55%). For 12 patients, 32 expansion treatments were undertaken between September 1997 and January 2002. The 12 patients included 3 women, 4 men, and 5 children with a mean age of 20 years (range, 45 days to 36 years). All patients had more than one period of treatment. The most common conditions treated were burns (n = 7), trauma (n = 1), congenital naevi (n = 2), and male pattern baldness (n = 2). Reconstruction of 12 large scalp defects has been performed with a 3.1% rate of major complications. Results show that tissue expansion is a safe and efficient but time-consuming technique for aesthetic scalp reconstruction, especially in the case of “sideburn” scenario or large defects. There was no significant alteration in ratio of complications although tissue expansions were made sequentially.

Effects of high dose corticosteroids in open rhinoplasty

BACKGROUND Although some studies about the effects of steroids on surgical trauma in closed or combined (closed and open together) rhinoplasty have been reported in the literature, still more information is needed in order to enlighten rhinoplasty surgeons. The purpose of this study is to evaluate the anti-inflammatory activity of steroids administered in high doses to prevent and decrease periorbital ecchymosis and oedema in patients who underwent open rhinoplasty with osteotomies by the same surgeon. This is the first study in open rhinoplasty alone. METHODS The study was performed on 40 patients, under general anaesthesia. Patients were divided randomly into five groups (eight patients in each group); the groups comprised: a single 250 mg dose of methylprednisolone (Group I), a single 500 mg dose of methylprednisolone (Group II), four 250 mg doses of methylprednisolone (Group III), four 500 mg doses of methylprednisolone (Group IV) and placebo (Group V). Digital photographs were taken of each patient on the first, third and seventh postoperative days. Scorings of eyelid swelling and ecchymosis were evaluated separately using a graded scale from 0 to (+) 4 by three observers, independently. Additionally, blood samples were taken for the evaluations of C-reactive protein (CRP), white blood cell (WBC) and erythrocyte sedimentation rate (ESR) on the same days. RESULTS Clinically and statistically significant difference was observed in the decrease of both ecchymosis and oedema, between the placebo and high dose methylprednisolone groups, which is effective to prevent and to decrease both the ecchymosis and oedema in open rhinoplasty with osteotomies. CRP was the most sensitive acute phase reactant among CRP, ESR and WBC. No complication was observed due to steroid usage. CONCLUSIONS We can confidently say that high dose methylprednisolone is effective in preventing and reducing both the periorbital ecchymosis and oedema in open rhinoplasty with osteotomies and it can be used safely for this purpose.

The use of high-density porous polyethylene as a custom-made nasal spreader graft.

The concept and technique of using high-density porous polyethylene (HDPP), a nonresorbable synthetic material, for nasal spreader grafts, are presented. This material is thought to be particularly useful in revision (secondary or tertiary) rhinoplasty, in which internal valve collapse frequently is confronted and septal cartilage often is unavailable because it has been harvested for spreader or other grafts. Sold as a thin plain sheet (0.85 × 38 × 50 mm) that can be cut to an appropriate size for spreader grafts, HDPP is a ready-to-use material commercially available on the market. Because HDPP permits ingrowths of fibrous tissue inside and around, it is a nonabsorbable material that stabilizes the upper lateral cartilages in their new position and maintains the appropriate internal valve angle. The authors used this material for 15 patients undergoing secondary (n = 12) and tertiary (n = 3) rhinoplasty because of valvular collapse. During the mean follow-up period of 16 months (range, 8–30 months), neither complication nor recurrence of airway obstruction occurred.