Percutaneous Cementoplasty for the Pelvis in Bone Metastasis: 12-Year Experience.

BACKGROUND: In advanced cancer patients, pelvic bone metastasis often causes pain and gait disturbance. The use of percutaneous bone cement [polymethylmethacrylate (PMMA)] injection for pain management and strengthening in pelvic bone metastasis has rarely been reported. To evaluate this method, we aimed to determine surgical outcomes and complications over a long-term follow-up period using a large patient group. PATIENTS AND METHODS: We retrospectively collected data from 178 patients who underwent percutaneous cementoplasty for pelvic metastatic lesions, 201 in total. Surgical outcomes evaluated included pain reduction and improvement of ambulation. Mortality within 1 month after procedure and pulmonary embolism caused by thrombus, fat, tumor emboli, or bone cement were investigated as surgical complications. For long-term survivors, pain relapse and mechanical failure were analyzed. The mean follow-up period was 12.6 months, and there were 159 fatalities at last follow-up. RESULTS: The mean regional pain numerical rating scale scores decreased from 6.1 preoperatively to 2.4 1 month after procedure (p < 0.01). Gait function was maintained, worsened, and uncheckable in 68%, 24%, and 8% of patients, respectively, 1 month after procedure. Of long-term survivors followed up for > 12 months (n = 53), there were no significant changes in serial plain radiographs, and regional pain aggravation was observed in 9%. Pulmonary cement embolism and bone cement implantation syndrome was observed in 11% and 10%, respectively. However, all patients with these complications were asymptomatic. CONCLUSIONS: Percutaneous cement injection into the pelvis is a feasible and safe palliative surgical option for patients with advanced malignancy in terms of pain reduction and maintenance of ambulatory function under regional anesthesia.

Preliminary results: use of multi-hole injection nails for intramedullary nailing with simultaneous bone cement injection in long-bone metastasis.

OBJECTIVE: For symptomatic metastasis of the long bones, intramedullary nailing has been the most accepted fixation method. Intramedullary nailing has effective control of pain, perioperative bleeding, and local tumor progression by augmentation with bone cement around the nail. Here, we report the preliminary results of a new surgical implant that allows for simultaneous injection of bone cement while inserting a percutaneous, flexible intramedullary nail. MATERIALS AND METHODS: We performed palliative surgeries for long-bone metastasis using a multi-hole injection nail (MIN) with multiple side holes in the distal one third. When the nail tip entered the metastatic cancer lesion, the bone cement injection was started, and continued until the nail was completely seated. Ten patients with advanced cancer underwent palliative surgery using the new implant with simultaneous bone cement injection for humeral (n = 4), femoral (n = 4), and tibial (n = 2) metastases. RESULTS: The mean operative time was 42 min (range, 36-52 min). The mean length of the injection nail was 23.0 cm (range, 18.0-33.0 cm), and the mean volume of cement was 28.0 ml (range, 14.0-40.0 ml). Marked pain palliation (p < 0.001) and functional recovery (p = 0.01) were verified. The mean Musculoskeletal Tumor Society (MSTS) functional score improved significantly from 12.5 at 6 weeks preoperatively, to 24.9 postoperatively. No acute postoperative complications, including cement embolism, occurred. CONCLUSION: This minimally invasive surgical method with MIN could be useful for stabilization of long-bone metastases in patients with advanced cancer.

Joint-preserving palliative surgery using self-locking screws of intramedullary nail and percutaneous cementoplasty for proximal humeral metastasis in the advanced cancer patients.

BACKGROUND: We introduced a palliative joint-preserving surgery using proximal self-locking screws of intramedullary (IM) nail and percutaneous cementoplasty (PC) in patients with proximal humeral metastases, including the head and neck, and evaluated the outcome of the surgical method. METHODS: Twenty-three patients (mean age = 63.0 ± 11.8 years, M:F = 14:9) had IM nailing with a self-locking screw system and PC for the treatment of humeral head and neck metastases. Usually, three proximal locking screws were inserted after IM nailing, and 20.9 ± 8.0 ml of polymethylmethacrylate (PMMA) bone cement was injected in the perimetal osteolytic area. RESULTS: Regional anesthesia with interscalene block was performed in 87.0% (20/23), and the duration of surgery (from anesthesia to awakening) was approximately 40-55 min. Red blood cell was not transfused intra- and/or postoperatively in 65.2% (15/23). The localized preoperative pain (visual analog scale (VAS), 8.2 ± 3.1) was gradually decreased at postoperative 1 week (VAS, 4.9 ± 2.1) and at 6 weeks (VAS, 2.9 ± 2.1) (P < 0.001). Among nine patients who underwent F-18-FDG PET/CT, the proximal humeral metastasis around PC showed improved, stable, and aggravated states in five (55.6%), three (33.3%), and one patient (11.1%), respectively. Meanwhile, 88.8% (8/9) of patients showed aggravation at the naive bone metastasis area. CONCLUSION: The selection of the self-locking screw type of the IM nail and PC was helpful in preventing fixation failure for joint-preserving palliative surgery in the proximal humeral metastasis.

Percutaneous Cementoplasty For Acetabulum In Patients With Bone Metastasis.

The purpose of this study is to demonstrate the surgical technique and to show the results of percutaneous cementoplasty (PC) for acetabular metastases using lateral approach under regional anesthesia. Forty-two cases underwent PC for acetabular metastases. The PC was performed using spinal anesthesia, lateral approach and fluoroscopic guidance. We assessed visual analogue scale (VAS) and revised musculoskeletal tumor society (MSTS) rating system and maximum standardized uptake value (SUVmax) of the acetabular lesion using F-18-FDG PET/CT before and after the PC. The mean injected volume of polymethylmethacrylamide to the pelvis was 21±11.8 ml. The mean of regional VAS (6.2±1.1 vs. 3.1±2.7, p<0.001), MSTS (10.3±3.9 vs. 18.3±3.2, p<0.001) and local SUVmax (8.6±5.2 vs. 5.7±3.6 , p = 0.012) on PET/CT showed significant reductions after surgery. Twenty-three patients (55%) died of disease at mean 11.8±4.8 months after surgery. PC using lateral approach and regional anesthesia could be a simple and safe surgical method for relieving pain and maintaining skeletal stability against acetabular metastasis.

Protein coverage on polymer nanolayers leading to mesenchymal stem cell patterning.

Interactions of gelatin and albumin with a photo-reactive diphenylamino-s-triazine bridged p-phenylene vinylene polymer (DTOPV) were examined by using surface plasmon resonance (SPR) spectroscopy to explore the effect of the polymer structure on protein coverage of DTOPV nanofilms. The SPR data revealed a significant increase of gelatin adsorption on UV-DTOPV nanofilms, while the adsorption of albumin was decreased by UV exposure in the time frame of the experiment. We also found that the selective adsorption of these proteins was highly dependent on the protein concentration; the highest selectivity of protein adsorption was obtained at the lowest concentration (3.5 µg ml(-1)), while no selective adsorption was confirmed at high concentrations (350 and 1000 µg ml(-1)). The selective attachment of mesenchymal stem cells (MSCs) was directly correlated with the selective adsorption of these proteins onto DTOPV nanofilms. The MSCs attachment onto UV-DTOPV films was promoted with only small mass coverage of gelatin, which led to MSC patterning onto the patterned DTOPV nanofilms successfully. The role of cell adhesion proteins that we found in this study will be a clue to elucidate the complex response of biomolecules on functional polymer nanolayers, and contribute to build up biocompatible surfaces on various advanced materials for the sake of cell engineering and medical implants.

MRI-guided navigation surgery with temporary implantable bone markers in limb salvage for sarcoma.

BACKGROUND: Technical errors during navigation-assisted bone tumor resection may occur by: (1) incorrect registration of images and corresponding anatomic points of bone sent to the navigation system; and (2) incorrect fusion of two or more images that have been transported to the navigation system. QUESTIONS/PURPOSES: We investigated new methods of navigation surgery to minimize technical errors during the registration and image fusion processes and specifically asked whether a navigated cannula probe would reduce unnecessary soft tissue dissection, and allow percutaneous registration and implantation of a reference base tracker in the margin of bone to be resected. METHODS: We performed direct MRI-guided navigation surgery without image fusion on a patient with osteosarcoma using absorbable pins as temporary implanted bone markers that prevent artifacts on MR images. RESULTS: Direct MRI-guided navigation surgery was possible using bone markers. A navigated cannula probe allowed percutaneous registration and a navigated blade-shaped probe provided a real-time check on the narrow osteotomy gap. The surgical procedure was facilitated by implantation of a reference base tracker on the margin of bone to be resected. CONCLUSIONS: Our modified technique of MRI-guided navigation surgery for patients with a malignant bone tumor may reduce processing errors by increased accuracy and be helpful for joint preserving surgery.

Stroma-free mass production of clinical-grade red blood cells (RBCs) by using poloxamer 188 as an RBC survival enhancer.

BACKGROUND: In vitro generation of red blood cells (RBCs) is an important alternative to donor RBCs. It was impossible, however, to generate a large quantity of RBCs due to necessity of supporting stromal cells or xenogeneic or human serum for in vitro culture, which had restrictions in safety, supplies, and expenses. In addition, the low viability of erythroblasts during terminal maturation in vitro required highly efficient production protocols. Here, we present a protocol for mass production of clinical-grade RBCs from cord blood (CB) CD34+ cells in stroma-free culture by using poloxamer 188 (P188), a polymer known to be cytoprotective against hydrodynamic stress. STUDY DESIGN AND METHODS: Umbilical CB CD34+ cells were cultured for 21 days in medium containing several cytokines, and roughly fibrin-eliminated CB derived plasma was added from Day 13. To enhance the final RBC production, P188 was added from Day 13 and the cell count and viability were compared with controls lacking P188. RESULTS: Erythroid expansion between Day 17 and Day 21 was significantly higher in cultures treated with P188, with a mean of 1.5 times and maximum of 3.6 times higher expansion than in controls lacking P188. The enhanced survival resulted from increased stability of the RBC membrane and decreased fragility. The erythroid cells were enucleated up to 95% and demonstrated hematologic variables similar to those of reticulocytes. CONCLUSION: This RBC production protocol is a simple stroma- and serum-free culture method ensuring enhanced viability of terminally mature erythroid cells and can be easily applicable to mass production of clinical-grade RBCs as well as erythropoiesis research.

Magnetic poly epsilon-caprolactone nanoparticles containing Fe3O4 and gemcitabine enhance anti-tumor effect in pancreatic cancer xenograft mouse model.

We prepared magnetic (Fe(3)O(4)) poly epsilon-caprolactone (PCL) nanoparticles (mean diameter 164 +/- 3 nm) containing an anticancer drug (gemcitabine) using emulsion-diffusion method in order to develop more efficient drug delivery for cancer treatment. Nanoparticles were smooth, well individualized and homogeneous in size. The values of magnetizations for the magnetic PCL nanoparticles were observed around 10.2 emu/g at 2000 Oe magnetic field intensity and showed super-paramagnetic property. In case of the drug, the drug loading contents was 18.6% and entrapment efficiency was 52.2%. The anti-tumor effects caused by these particles were examined using nude mice bearing subcutaneous human pancreatic adenocarcinoma cells (HPAC) in vivo. We divided that these mice were randomly assigned to one of five treatment groups for experimental contrast. The antitumor effect was showed with 15-fold higher dose when compared to free gemcitabine. From the result, the magnetic PCL nanoparticles may provide a therapeutic benefit by delivering drugs efficiently to magnetically targeted tumor tissues, thus achieving safe and successful anti-tumor effects with low toxicity.

Proximal Tibia Chondroblastoma Treated With Curettage and Bone Graft and Cement Use.

Chondroblastoma has a predilection for the epiphyses or apophyses of long tubular bones. Management of lesions in the proximal tibia is challenging because it is difficult to gain access to intraepiphyseal lesions for completion of curettage. From October 2007 to December 2011, 9 patients with de novo chondroblastoma of the proximal tibia underwent surgery at the authors' institution. All patients initially presented with pain, and 5 patients had limitation of range of motion of the ipsilateral knee. Four lesions abutted the tibial attachment sites of the cruciate ligaments. Surgical procedures included intralesional tumor curettage, additional burring, and packing of the defect with bone graft and/or bone cement. The extra-articular approach was used according to tumor location. The medial or lateral parapatellar approach was used when the tumor was located in the anterior two-thirds of the horizontal plane. When a lesion was located in the posterior third, the posteromedial or posterolateral approach was used as the lesion was cornered. Mean duration of follow-up was 47.2 months (range, 27-80 months). No local recurrence or pulmonary metastasis was noted at latest follow-up. Mean functional score was 29.3 points (range, 28-30 points). All patients fully recovered range of motion in the affected knee. No avulsion fracture or anteroposterior instability of the knee joint was detected. Results of the current study suggest that intralesion curettage followed by additional burring with an extra-articular approach is a successful treatment option for chondroblastoma of the proximal tibia.

Minimally invasive surgery for femoral neck fractures using bone cement infusible hollow-perforated screw in high-risk patients with advanced cancer.

OBJECTIVE: Pathologic or osteoporotic femoral neck fractures usually treated with joint replacement surgery rather than joint-preserving surgery because multiple screw fixation has a high risk for fixation failure and nonunion as well as the need for a postoperative protection period. However, joint-preserving surgery might be preferable in high-risk patients with short life expectancy due to advanced disease. Recently introduced hollow-perforated screws are devices for achieving percutaneous fixation by simultaneous injection to the weak bone area through its multiple side holes. We report our experience of surgical treatment of femoral neck fractures by controlled bone cement injection into the femoral head and neck through a modified hollow-perforated screw in patients with advanced cancer. METHODS: We modified the hollow perforated screw with variable placing of screw-side holes as fracture patterns. Polymethylmethacrylate (PMMA) bone cement was injected through the screw holes to control its injection into the selective areas of the femoral head and neck while avoiding the fracture sites. One or two of these were fixed percutaneously in 12 patients who have Garden stage I or II femoral neck fractures in the advanced state of advanced cancer. Seven patients had pathologic fracture by metastatic cancer, but 5 had osteoporotic fractures. RESULTS: Eleven patients died a mean of 4.1 months after surgery and 1 patient lived with ability to walk for 48 months. Sixteen modified hollow perforated-screws and 16 standard cannulated screws were used for fixation. The mean volume of cement injection was 13.8 ml. The complication developed in 4 patients: cement leakage to the hip joint in 2 patients, subtrochanteric fracture in 1 patient (5 months after surgery) and fixation failure in 1 patients (2 months after surgery). Nine patients could walk with or without a walking aid, and all others also could return to the prefracture-ambulation state with effective pain relief on the third postoperative day. CONCLUSION: This current surgical method could be useful in patients with short life expectancy because of quick pain relief, early return to ambulation, simple operative procedures and short hospital stay. The modified hollow perforated screw which has a diversity of side hole locations for the regulation of bone cement injection into the planned area seems useful for selective femoral neck fractures.

Increased production of bacterial cellulose by Acetobacter sp. V6 in synthetic media under shaking culture conditions.

Acetobacter strains are bacteria that can synthesize cellulose when grown in a complex medium containing glucose. The effect of the components of a synthetic medium on bacterial cellulose (BC) production by a newly isolated Acetobacter sp. V6 in shaking cultures was investigated. BC production was dependent on the presence of MgSO4 x 7H2O and cosubstrates such as ethanol and lactic acid in the medium. The optimal synthetic medium contained 1.5% glucose, 0.2% (NH4)2SO4, 0.3% KH2PO4, 0.3% Na2HPO4 x 12H2O, 0.08% MgSO4 x 7H2O, 0.0005% FeSO4 x 7H2O, 0.0003% H3BO3, 0.00005% nicotinamide, and 0.6% ethanol. A maximum BC concentration of 4.16 g/l was achieved after 8 days of cultivation at 200 rpm. The production of BC by Acetobacter sp. V6 was higher in synthetic medium than complex medium (Hestrin and Schramm medium) traditionally used for Acetobacter strains.

Palliative percutaneous stabilization of lower extremity for bone metastasis using flexible nails and bone cement.

OBJECTIVE: Percutaneous stabilization (PS; percutaneous flexible nailing and intramedullary bone cement injection) was performed at lower extremity long bones in patients with multiple bone metastases with short life expectancy to get mechanical stability and local tumor control. We evaluated the usefulness of PS by clinical status, F-18-FDG PET-CT and bone scintigraphy (BS). METHODS: Patients comprised 15 patients (total 20 sites) who had undergone PS for the metastatic bone tumors of lower extremity long bones (femur and tibia). After percutaneous flexible nailing, bone cement was injected (mean amount=15.5±6.4 ml). Patients' clinical status was evaluated by visual analog scale (VAS). Qualitative assessment of PET-CT and BS was categorized by improved, stable and aggravated states of PS lesion. Quantitative assessment of PET-CT was performed by maximum and mean standardized uptake value (SUVmax and SUVmean). RESULTS: PS was performed in all of the patients without complication, and showed significant pain improvement of VAS (7.2±0.2 vs. 2.8±0.3, P<0.001). PS lesion showed improved state in 65% (13/20) and stable state in 35% (7/20). However, naive bony metastatic lesion showed mostly aggravated state in 90% (19/20) in the same patients, which was significantly different compared with PS lesion (P<0.001). In PS lesion, SUVmax (10.1±6.9 vs. 7.1±5.2, P=0.008) and SUVmean (6.2±4.8 vs. 4.6±3.7, P=0.008) showed significantly decreased uptake after PS. CONCLUSION: By PS in lower extremity long bones, patients can reduce regional pain, and has the possibility of local tumor control. PS can be performed for lower extremity bone metastasis in poor general condition to perform conventional intramedullary nailing.

Noninvasive photodetachment of stem cells on tunable conductive polymer nano thin films: selective harvesting and preserved differentiation capacity.

Viable mesenchymal stem cells (MSCs) were efficiently and selectively harvested by near-infrared (NIR) light using the photothermal effect of a conductive polymer nano thin film. The poly(3,4-ethylenedioxy thiophene) (PEDOT)-coated cell culture surfaces were prepared via a simple and fast solution-casting polymerization (SCP) technique. The absorption of PEDOT thin films in the NIR region was effectively triggered cell harvesting upon exposure to an NIR source. By controlling the NIR absorption of the PEDOT film through electrochemical doping or growing PEDOT with different thin film thickness from 70 to 300 nm, the proliferation and harvesting of MSCs on the PEDOT surface were controlled quantitatively. This light-induced cell detachment method based on PEDOT films provides the temporal and spatial control of cell harvesting, as well as cell patterning. The harvested stem cells were found to be alive and well proliferated despite the use of temperature increase by NIR. More importantly, the harvested MSCs by this method preserved their intrinsic characteristics as well as multilineage differentiation capacities. This PEDOT surfaces could be used for repetitive culture and detachment of MSCs or for efficient selection or depletion of a specific subset from heterogeneous population during culture of various tissue-derived cells because there were no photodegradation and photobreakage in the PEDOT films by NIR exposure.

Micropatterns of double-layered nanofiber scaffolds with dual functions of cell patterning and metabolite detection.

This paper describes the development of multi-functional nanofiber scaffolds consisting of multiple layers of nanofiber scaffolds and nanofiber-incorporated poly(ethylene glycol) (PEG) hydrogels. As a proof-of-concept demonstration, we fabricated micropatterned polymeric nanofiber scaffolds that were capable of simultaneously generating cellular micropatterns within a biomimetic environment and detecting cellular metabolic products within well-defined microdomains. To achieve this goal, we designed nanofiber scaffolds with both vertical and lateral microdomains. Vertically heterogeneous structures that were responsible for multi-functionality were realized by preparing double-layered nanofiber scaffolds consisting of an antibody-immobilized bottom layer of nanofibers and an upper layer of bare polystyrene (PS) nanofibers by a two-step sequential electrospinning process. Photopatterning of poly(ethylene glycol) (PEG) hydrogel on the electrospun nanofibers produced laterally heterogeneous micropatterned nanofiber scaffolds made of hydrogel microwells filled with a nanofibrous region, which is capable of generating cell and protein micropatterns due to the different interactions that cells and proteins have with PEG hydrogels and nanofibers. When HepG2 cells were seeded into resultant nanofiber scaffolds, cells selectively adhered within the 200 µm × 200 µm PS fiber microdomain and formed 180.2 ± 6.7 µm spheroids after 5 days of culture in the upper layer. Furthermore, immobilized anti-albumin in the bottom layer detected albumin secreted by micropatterned HepG2 cells with higher sensitivity than flat PS substrates, demonstrating successful accomplishment of dual functions using micropatterned double-layered nanofiber scaffolds.

Minimally invasive surgery of humeral metastasis using flexible nails and cement in high-risk patients with advanced cancer.

This study was conducted to evaluate the preliminary outcome of palliative minimally invasive surgery for humeral metastasis in patients who have multiple advanced cancers with short life expectancy. Percutaneous Ender nailing and direct transcortical intramedullary cementing were performed on a total of 15 patients with metastatic disease of the humerus. The origins of the cancers were the lung (n=9), breast (n=3), colon (n=2) and liver (n=1). Each patient had multiple unresectable organic metastases and proved to be at high risk for anesthesia and bloody surgery. All procedures were performed under regional anesthesia and fluoroscopic guidance. The mean amount of intramedullary cement injection after Ender nailing was 13.4ml. The mean of the numeric rating scale (NRS) score for pain decreased from 9.6 points before surgery to 3.6 points after surgery (P<0.001). The mean of the Musculoskeletal Tumor Society (MSTS) functional score increased from 10.6 points before surgery to 19.9 points after surgery (P<0.001). Seven patients died within 7 months. There were no complications associated with cement leakage, fixation failure and surgical wound even in cases of early postoperative radiation or chemotherapy. Percutaneous flexible nailing along with intramedullary cementing could be a useful minimally invasive surgical method for the palliation of humeral metastasis in selective terminal cancer patients by providing immediate reliable fixation and effective pain relief.

Grafting using injectable calcium sulfate in bone tumor surgery: comparison with demineralized bone matrix-based grafting.

BACKGROUND: Injectable calcium sulfate is a clinically proven osteoconductive biomaterial, and it is an injectable, resorbable and semi-structural bone graft material. The purpose of this study was to validate the clinical outcomes of injectable calcium sulfate (ICS) grafts as compared with those of a demineralized bone matrix (DBM)-based graft for filling in contained bony defects created by tumor surgery. METHODS: Fifty-six patients (41 males and 15 females) with various bone tumors and who were surgically treated between September 2003 and October 2007 were included for this study. The patients were randomly allocated into two groups, and either an ICS graft (28 patients) or a DBM-based graft (28 patients) was implanted into each contained defect that was developed by the surgery. The radiographic outcomes were compared between the two groups and various clinical factors were included for the statistical analysis. RESULTS: When one case with early postoperative pathologic fracture in the DBM group was excluded, the overall success rates of the ICS and DBM grafting were 85.7% (24/28) and 88.9% (24/27) (p > 0.05), respectively. The average time to complete healing was 17.3 weeks in the ICS group and 14.9 weeks in the DBM group (p > 0.05). Additionally, the ICS was completely resorbed within 3 months, except for one case. CONCLUSIONS: Although the rate of resorption of ICS is a concern, the injectable calcium sulfate appears to be a comparable bone graft substitute for a DBM-based graft, with a lower cost, for the treatment of the bone defects created during surgery for various bone tumors.

Advanced c-myc antisense (AVI-4126)-eluting phosphorylcholine-coated stent implantation is associated with complete vascular healing and reduced neointimal formation in the porcine coronary restenosis model.

An advanced six-ring morpholino backbone c-myc antisense (AVI-4126) was shown to inhibit c-myc expression and intimal hyperplasia after local catheter delivery in a porcine balloon injury model. The purpose of this study was to investigate the effects of an AVI-4126-eluting phosphorylcholine-coated (PC) stent on c-myc expression restenosis and vascular healing after stent implantation in porcine coronary arteries. PC stents were loaded with AVI-4126 using soak trap. Nine pigs underwent AVI-4126 PC coronary stent implantation (two stents/animal). Two to six hours postprocedure, three pigs were sacrificed and stented segments were analyzed by Western blot for c-myc expression. In chronic experiments, six pigs (12 stent sites) were sacrificed at 28 days following intervention and vessels were perfusion-fixed. High-performance liquid chromatography analysis of plasma samples showed minimal presence of the antisense. Western blot analysis of the stented vessels demonstrated inhibition of c-myc expression at 2 and 6 hr after procedure. Quantitative histologic morphometry showed that the neointimal area was significantly reduced (by 40%) in the antisense-coated group compared with control (2.3 +/- 0.7 vs. 3.9 +/- 0.8 mm(2), respectively; P = 0.0077). Immunostaining and electron microscopy demonstrated complete endothelialization, without fibrin deposition, thrombosis, or necrosis in all implanted stents. In the porcine coronary model, an advanced c-myc-eluting PC stent blocked c-myc expression and significantly inhibited myointimal hyperplasia and allowed complete reendothelialization and healing response.