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Transient in vivo thrombus deposition onto polymeric biomaterials: role of plasma fibronectin
Ihlenfeld, J. V., T. R. Mathis, et al. (1978), Trans Am Soc Artif Intern Organs 24: 727-35.

Transition of mechanical property of porous alginate scaffold with cells during culture period
Sakai, S., H. Masuhara, et al. (2005), J Biosci Bioeng 100(1): 127-9.
Abstract: The rupture forces of porous alginate scaffolds seeded with hepatocytes or fibroblast-like cells increased during 3 d of culture and then decreased. The phenomenon was independent of the number of viable cells within the scaffolds, but dependent on protein adsorption to the alginate as well as a reduction in the degree of crosslinks of the calcium-alginate gel.

Transitory oxidative stress in L929 fibroblasts cultured on poly(epsilon-caprolactone) films
Serrano, M. C., R. Pagani, et al. (2005), Biomaterials 26(29): 5827-34.
Abstract: Poly(epsilon-caprolactone) (PCL) is considered as a potential substrate for wide medical applications. In previous studies we carried out the in vitro biocompatibility assessment of PCL films using L929 mouse fibroblasts, obtaining good cell behaviour but a transitory stimulation of mitochondrial activity and cell retraction. Reactive oxygen species (ROS), mainly formed in mitochondria, can impair the function of several cellular components and produce cell oxidative stress by changing the normal red-ox status of the major cell antioxidants as glutathione. The aim of this study was to measure intracellular ROS production and glutathione content of L929 fibroblasts cultured on PCL films. Cell size, internal complexity, cell cycle and lactate dehydrogenase release were also evaluated. The films were treated with NaOH before culture to improve the cell-polymer interaction. PCL induces a transitory but significant oxidative stress in L929 fibroblasts. The treatment of PCL films with NaOH reduces this effect. PCL also induces transitory changes on cell size and complexity. Nevertheless, after 7 days in culture, cells reach control levels for all the studied parameters. Neither cell cycle nor membrane integrity appears affected by this oxidative stress respect to control cells at any culture time. These results underline the cytocompatibility of PCL films and, therefore, its potential utility as a suitable scaffold in tissue engineering.

Translocation of double-strand DNA through a silicon oxide nanopore
Storm, A. J., J. H. Chen, et al. (2005), Phys Rev E Stat Nonlin Soft Matter Phys 71(5 Pt 1): 051903.
Abstract: We report double-strand DNA translocation experiments using silicon oxide nanopores with a diameter of about 10 nm. By monitoring the conductance of a voltage-biased pore, we detect molecules with a length ranging from 6557 to 48 500 base pairs. We find that the molecules can pass the pore both in a straight linear fashion and in a folded state. Experiments on circular DNA further support this picture. We sort the molecular events according to their folding state and estimate the folding position. As a proof-of-principle experiment, we show that a nanopore can be used to distinguish the lengths of DNA fragments present in a mixture. These experiments pave the way for quantitative analytical techniques with solid-state nanopores.

Transplant of mesenchymal stem cells and hydroxyapatite ceramics to treat severe osteochondral damage after septic arthritis of the knee
Adachi, N., M. Ochi, et al. (2005), J Rheumatol 32(8): 1615-8.
Abstract: We describe a 21-year-old man with a large osteochondral defect of the knee after septic arthritis, successfully treated by transplant of mesenchymal stem cells (MSC) from bone marrow and a new type of interconnected porous hydroxyapatite ceramic (IP-CHA). We confirmed successful cartilage-like tissue regeneration by a second arthroscopy. Biopsy of the repaired tissue revealed cartilage-like regeneration and bone formation. We were able to regenerate new bone and cartilage-like tissue in a one-stage operation, without sacrificing autologous bone or other tissue. This cultured MSC and IP-CHA hybrid material transplant represents a novel treatment for a severe osteochondral defect after septic arthritis.

Transplantation of bioencapsulated bone marrow stem cells improves hepatic regeneration and survival of 90% hepatectomized rats: a preliminary report
Liu, Z. C. and T. M. Chang (2005), Artif Cells Blood Substit Immobil Biotechnol 33(4): 405-10.
Abstract: We transplanted bioencapsulated bone marrow stem cells intraperitoneally into 90% hepatectomized rats and found that this increases both the rates of hepatic regeneration and survival of the animals. Bone marrow cells isolated from Wistar rats were bioencapsulated using alginate-polylysine-alginate method. These bioencapsulated bone marrow cells were transplanted intraperitoneally into 90% hepatectomized syngeneic wistar rats. Control groups included 90% hepatectomized group receiving intraperitoneal injection of either empty microcapsules or free bone marrow cells. Unlike the control groups, transplantation of bioencapsulated bone marrow cells improved the survival of 90% hepatectomized rats, with an efficacy similar to that of bioencapsulated hepatocytes or free hepatocytes. These results suggest that syngeneic bioencapsulated bone marrow stem cells can increase the survival rates of 90% hepatectomized rats. We also discuss the potential for a new alternative to hepatoctye transplantation for cellular therapy of acute liver failure. In particular, bone marrow stem cells can be obtained from the same patient with no immunorejection, whereas in hepatocyte transplant, immunosuppressant will be needed to prevent immunorejection of the donor hepatocytes.

Transplantation of chondrocytes seeded on collagen-based scaffold in cartilage defects in rabbits
De Franceschi, L., B. Grigolo, et al. (2005), J Biomed Mater Res A 75(3): 612-22.
Abstract: Recent success in tissue engineering by restoring cartilage defects by transplanting autologous chondrocyte cells on a three-dimensional scaffold has prompted the improvement of this therapeutic strategy. Here we describe a new approach investigating the healing of rabbit cartilage by means of autologous chondrocytes seeded on a biomaterial made of an equine collagen type I-based scaffold. Full-thickness defects were created bilaterally in the weight-bearing surface of the medial femoral condyle of both femora of New Zealand male rabbits. The wounds were then repaired by using both chondrocytes seeded on the biomaterial and biomaterial alone. Controls were similarly treated but received either no treatment or implants of the delivery substance. Histological examination of the reconstructed tissues at 1, 3, 6, and 12 months after transplantation showed that at 1 and 3 months there was no formation of reconstructed tissue in any of the groups evaluated; after 6 months there was evidence of a newly regenerated tissue with some fibrocartilaginous features only in the group treated with biomaterial-seeded cells, and at 12 months a more organized tissue was evident in the same group. With regards to the group transplanted with biomaterial alone and the untreated control group, there was no evidence of new tissue production. These results advocate the use of this collagen-based scaffold for further in vivo studies on large size animals and, finally, in human clinical trials for the treatment of knee cartilage defects. (c) 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005.

Transplantation of new autologous biomaterials into jaw cleft
Kawata, T., S. Kohno, et al. (2001), J Int Med Res 29(4): 287-91.
Abstract: This study compared bone-marrow grafting using chondroid or fibula bone grafts transplanted into simulated alveolar bone defects in mice. The osteogenic procedure was also investigated. As an experimental model of the maxillary alveolar bone cleft, suitable for testing bone-inductive materials, a surgical trephine with a low-speed dental engine was used to form critical-sized defects in the pre-maxillary bones of male mice. Distraction osteogenesis was performed using an external fixation device. The osteotomy site was surrounded by an external callus, consisting of hyaline cartilage, that contained a large quantity of chondroid bone. Transplanted bone within chondroid bone was characterized by bone formation and remodelling 30 days post-transplantation, and bone adhesion following chondroid bone grafting was better than adhesion following fibula grafting. The present findings are the first to demonstrate the potential of chondroid bone transplantation as a new therapeutic system of bone grafting, suitable for bone substitution in craniofacial bone defects.

Treating chronic total occlusions using subintimal tracking and reentry: the STAR technique
Colombo, A., G. W. Mikhail, et al. (2005), Catheter Cardiovasc Interv 64(4): 407-11; discussion 412.
Abstract: Successful recanalization of coronary total occlusions (CTOs) remains an area where improvements are needed. We propose an approach similar to the one utilized in treating some peripheral artery occlusions and aimed to create a subintimal dissection with distal reentry. A 0.014' hydrophilic wire with a J-configuration is utilized for this purpose. We applied this technique to CTO of native coronaries in 31 patients where previous attempts failed in 21 of them (67%). The right coronary artery (RCA) was the index vessel in 87% of patients. Recanalization of the vessel and of most of distal branches was achieved in 21 patients; patency of at least one major distal branch was achieved in 9 patients. Drug-eluting stents (DESs) were implanted in 53% of patients. Three patients had intraprocedural vessel perforation without consequences. Five patients (16%) had in-hospital non-Q-wave myocardial infarction. No other adverse events occurred at a mean follow-up of 5.1 +/- 3.7 months except for one noncardiac death. Angiographic follow-up was performed in 21 (67%) patients and 53% of them developed restenosis. Reintervention on the target vessel was performed in 11 patients (52%). Complete success with the procedure was originally obtained in 8 of the 10 patients who did not develop restenosis and in 8 of them DESs were originally implanted. This technique appears a promising approach to recanalize difficult total occlusions, particularly the ones localize on the RCA, which has the most important side branches located distally.

Treating keratoconus with intacs corneal ring segments
Hellstedt, T., J. Makela, et al. (2005), J Refract Surg 21(3): 236-46.
Abstract: PURPOSE: To assess the safety and efficacy of Intacs inserts for the treatment of mild to moderate keratoconus. METHODS: In a nonrandomized prospective clinical trial, 50 eyes of 37 patients with mild to moderate keratoconus were implanted with asymmetrical pairs of Intacs segments. Patients were interviewed and observed preoperatively and 24 hours, 1 week, 1, 3, 6, and 12 months postoperatively. Main outcome measures were uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), refraction, satisfaction with vision and trouble with vision, Visual Function-7 score, and surgically induced change in corneal astigmatism. RESULTS: Of the 50 operations performed, 92% were successful. Mean follow-up was 6.3 +/- 3.2 months. In 4 (8%) eyes, both Intacs segments were removed. In addition, 7 refractive adjustments in 7 eyes were performed successfully to improve visual and surgical outcome. Both BSCVA and UCVA improved throughout follow-up. Visual functioning index improved from 61.6 +/- 21.1 to 80.8 +/- 22.5, and the percentage of satisfaction with vision improved from 24.3% to 87.5% at 12 months. Vector analysis of astigmatism correction showed that the mean change in corneal astigmatism was 2.9 +/- 2.9 D at 6 months postoperatively. By selecting patients in whom astigmatism correction was best (index of success >0.5), an analysis was performed to determine individual factors important in successful surgery. Preoperatively these 11 (22%) eyes did not differ significantly from the remaining eyes and the only significant value was low K readings in the flat axis. CONCLUSIONS: Asymmetric Intacs placement improves BSCVA and UCVA and reduces astigmatism in patients with mild to moderate keratoconus. The procedure of Intacs placement is safe and effective. The change in astigmatism correction is unpredictable.

Treatment of a venous leg ulcer with a honey alginate dressing
van der Weyden, E. A. (2005), Br J Community Nurs Suppl: S21, S24, S26-7.
Abstract: The management of chronic wounds such as venous ulcers is a common and long-term issue with the aging population. Non-standard treatment that is both medically and financially effective needs to be identified. Honey has been used for its healing properties for centuries and has been used to successfully heal wounds including pressure-ulcers in our care facility. However, there is not much evidence for its use in treating venous ulcers. To this end, I trialed the use of a honey-impregnated alginate dressing on a man who had a long-standing history of venous ulcers on his leg with the aim of evaluating the effectiveness of honey as an alternative treatment to the current wound management therapies. The honey seemed to act as an effective antibacterial, anti-inflammatory and deodorizing dressing, with total healing of the ulcer achieved. This result, together with past successes with the use of honey alginate on ulcerated wounds, has led to this product becoming mainstream in the treatment of chronic wounds within our care facility.

Treatment of bacterial biofilms on polymeric biomaterials using antibiotics and ultrasound
Johnson, L. L., R. V. Peterson, et al. (1998), J Biomater Sci Polym Ed 9(11): 1177-85.
Abstract: New studies on the effect of frequency and duration of exposure upon the ultrasonic enhanced action of gentamicin against biofilms of Escherichia coli are presented in this paper. Ultrasound was applied at clinical levels which would not harm human tissue. The study on frequency indicated that lower frequencies produce higher levels of killing. The results of the timed experiment indicate that complete sterilization of a 14-h biofilm can be achieved after 6 h of exposure. These findings are significant because they show that biofilms can be reduced to zero reproductive ability as assessed by plate counting.

Treatment of distal radial fractures with grafting and K-wiring
Willcox, N., I. Kurta, et al. (2005), Acta Orthop Belg 71(1): 36-40.
Abstract: We present a series of 10 distal radius fractures treated with either bone substitute or xenograft, and Kapandji's technique (intra-focal threaded Kirschner wires which lever on the graft before penetrating the opposite diaphyseal cortex). The Kirschner wires are buried. Long-term follow-up (one to five years, mean 2.8 years) shows very little secondary displacement (up to 3 mm loss of radial height on the antero-posterior views and none on the sagittal views), excellent tolerability and integration of substitute and good function. The above operative technique has the advantage to allow immediate mobilisation of the wrist.

Treatment of experimental immune complex glomerulonephritis by sodium alginate
Mirshafiey, A., Z. Borzooy, et al. (2005), Vascul Pharmacol 43(1): 30-5.
Abstract: We have studied the therapeutic efficacy of the sodium alginate in experimental immune complex glomerulonephritis. Bovine serum albumin (BSA) nephritis was induced in rats by a subcutaneous immunization and daily intravenous administration of BSA. Sodium alginate at two different doses (25 and 50 mg/kg) was administered intraperitoneally at regular 72-h intervals for 6 weeks. Onset of treatment was day 42. Urinary protein was measured weekly and serum anti-BSA antibody was assessed by ELISA method at different intervals. Animals were euthanized at the 12th experimental week and blood samples and kidney specimens were obtained. BUN, serum creatinine and serum cholesterol and triglyceride were measured at the time of sacrifice. Kidney specimens were processed for light and immunofluorescent microscopic examination. The tolerability and inhibitory effect of LVA on matrix metalloproteinase 2 (MMP-2) were tested using WEHI-164 cell line and zymography method. Results of this experiment showed that treatment with sodium alginate could significantly reduce the urinary protein excretion and serum creatinine in treated rats vs. nontreated controls. Anti-BSA antibody titers were lower in treated rats than in controls at the 12th week post-immunization. There was no significant difference in the level of BUN and serum lipids between two groups. Whereas, glomerular hypercellularity, PMN infiltration and glomerular deposition of BSA were less intense in treated rats vs. controls. Moreover, in vitro examinations revealed that treatment with LVA, as a very safe agent could diminish MMP-2 activity. These results suggest that treatment with sodium alginate as a new immunosuppressive agent can reduce proteinuria, inhibit MMP-2 activity and suppress the antibody production as well as the development of glomerular lesions in a rat model of immune complex glomerulonephritis.

Treatment of fistulas-in-ano with fibrin sealant in combination with intra-adhesive antibiotics and/or surgical closure of the internal fistula opening
Singer, M., J. Cintron, et al. (2005), Dis Colon Rectum 48(4): 799-808.
Abstract: PURPOSE: The treatment of fistulas-in-ano with fibrin sealant injection has been moderately successful. Failures can be caused by persistent infection within the tract or early expulsion of the clot. In an attempt to improve the success rate, we examined three modifications of the sealant procedure: the addition of cefoxitin to the sealant, surgical closure of the primary opening, or both. METHODS: A prospective, randomized, clinical trial was performed in which patients were treated with Tisseel-VH fibrin sealant according to previously published procedures. In addition, patients were randomized to receive intra-adhesive cefoxitin, surgical closure of the primary opening, or both modifications. Cefoxitin, 100 mg, was added to the sealant for patients randomized to receive intra-adhesive antibiotics. For the appropriate patients, the primary fistula opening was closed with a 3-0 absorbable suture. If fistulas failed to heal, patients were offered a single retreatment with sealant. RESULTS: Twenty-four patients were treated in the cefoxitin arm, 25 in the closure arm, and 26 in the combined arm. Median duration of fistulas was 12 months. Patients were followed for a mean of 27 months postoperatively. There was no postoperative incontinence or complications related to the sealant itself. Initial healing rates were 21 percent in the cefoxitin arm, 40 percent in the closure arm, and 31 percent in the combined arm (P = 0.35). One of five patients in the cefoxitin arm, one of seven patients in the closure arm, and one of six patients in the combined arm were successfully retreated; final healing rates were 25, 44, and 35 percent respectively (P = 0.38). CONCLUSIONS: Treatment of fistula-in-ano with fibrin sealant with closure of the internal opening was somewhat more successful than sealant with cefoxitin or the combination, however this did not achieve statistical significance. None of the three modifications were more successful than historic controls at our institution treated with sealant alone. Therefore, the addition of intra-adhesive cefoxitin, closure of the internal opening, or both are not recommended modifications of the fibrin sealant procedure.

Treatment of human class II furcation defects using connective tissue grafts, bioabsorbable membrane, and resorbable hydroxylapatite: a comparative study
Belal, M. H., F. A. Al-Noamany, et al. (2005), J Int Acad Periodontol 7(4): 114-28.
Abstract: OBJECTIVE: To evaluate clinical outcomes and assess digital subtraction radiographic changes after using bioabsorbable membrane (polyglycolic acid/polylactic acid--PGA/PLA) or a connective tissue graft (CTG) as a barrier, with or without resorbable hydroxylapatite (HA Resorb) in the treatment of mandibular class II furcations. METHODS: Fifty furcations in twenty patients with chronic periodontitis were divided into five treatment groups: (I) PGA/PLA; (II) PGA/PLA and resorbable hydroxylapatite; (III) CTG; IV) CTG and resorbable hydroxylapatite; and (V) flap debridement alone (control). Vertical and horizontal probing depths, vertical probing attachment level, gingival recession and standardized periapical radiographs were obtained at baseline and at 3, 6 and 12 months post-operatively. At 12 months, the treated teeth were exposed by re-entry to verify clinical results. RESULTS: All experimental groups (I, II, III and IV) showed statistically significant improvement in the clinical parameters and bone density as compared to the control group. However, no statistically significant differences were observed among any of the experimental groups. Percentages of complete furcation closure and sites still defined as class II furcations were, respectively, as follows: 40% and 20-30% for groups II and IV; 20% and 40% for groups I and III; 0% and 80% for control. Groups II and IV showed significant radiographic changes in bone gain at both 6 and 12 months, while groups I and III showed significant changes only at 12 months. CONCLUSIONS: (1) Guided tissue regeneration (GTR) therapy with or without resorbable hydroxylapatite showed significantly favorable results clinically and radiographically compared to flap debridement alone. (2) GTR plus resorbable hydroxylapatite (groups II and IV) showed higher percentages of complete furcation closure and more bone gain than GTR alone (groups I and III). (3) CTG may be used as an alternative to PGA/PLA bioabsorbable membrane with comparable potential. (4) Digital subtraction radiography may give higher accuracy in assessing results of periodontal therapy.

Treatment of small defects adjacent to oral implants with various biomaterials
Becker, W. (2003), Periodontol 2000 33: 26-35.

Treatment of wide, shallow, and predominantly 1-wall intrabony defects with a bioabsorbable membrane: a randomized controlled clinical trial
Aimetti, M., F. Romano, et al. (2005), J Periodontol 76(8): 1354-61.
Abstract: BACKGROUND: The regenerative therapy of non-contained intrabony defects achieves better results when bioabsorbable membranes are combined with a filling material. The purpose of the present study was to analyze clinical and radiographic effectiveness of a space-making bioabsorbable membrane in the treatment of wide and shallow intrabony defects characterized by a relevant 1-wall component. METHODS: Eighteen pairs of angular bone defects were selected in 18 healthy, non-smoking patients (age range 30 to 66 years). Prior to the surgical phase, patients were enrolled in a strict periodontal program including oral hygiene instructions and scaling and root planing (presurgical full-mouth plaque score <10%). Using a split-mouth design, 18 sites were randomly assigned to receive guided tissue regeneration (GTR) using a bioabsorbable membrane (test group) and 18 to receive open flap debridement alone (control group). Clinical treatment outcome was evaluated 12 months postoperatively for changes in probing depth (PD), clinical attachment level (CAL), and position of gingival margin (REC) and radiographically for bone changes. Results: Open flap debridement and GTR yielded statistically significant (P<0.0001) PD reduction (2.39+/- 0.92 mm and 3.44+/- 0.78 mm), CAL gain (1.50+/- 0.99 mm and 2.89 +/- 0.90 mm), increased REC (-0.89 +/- 0.58 mm and -0.56 +/- 0.92 mm) and bone fill (1.05+/- 0.94 mm and 2.13+/- 1.21 mm) when 12-month data were compared to baseline. The differences between test and control groups were statistically significant for all parameters (P<0.007) except for REC (P=0.25). CONCLUSION: The use of this bioabsorbable membrane would seem to be effective in the treatment of intrabony defects with unfavorable architecture without the use of filling materials.

Treatment options following single-rooted tooth removal: a literature review and proposed hierarchy of treatment selection
Fugazzotto, P. A. (2005), J Periodontol 76(5): 821-31.
Abstract: BACKGROUND: Alveolar bone changes following tooth extraction have been well documented and have given rise to a number of treatment approaches. Included in these approaches are placement of various grafting materials, immediate implant placement, and a combination of both. METHODS: A review of all pertinent literature discussing regenerative therapy at the time of tooth extraction or immediate implant placement with or without concomitant regenerative therapy was carried out. RESULTS: A clinically-based hierarchy of treatment selection following extraction of single rooted teeth is proposed, based upon the available literature and clinical experience. The role of patient phenotype is considered. CONCLUSION: Utilization of the proposed hierarchy of treatment selection affords a logical framework within which to predictably treat a variety of patients.

Tricalcium phosphate and glutaraldehyde crosslinked gelatin incorporating bone morphogenetic protein--a viable scaffold for bone tissue engineering
Yang, S. H., C. K. Hsu, et al. (2005), J Biomed Mater Res B Appl Biomater 74(1): 468-75.
Abstract: Bone defects caused by various etiologies must be filled with suitable substances to promote bone repair. Autogenous iliac crest graft is most frequently used, but is often associated with morbidities. Several bone graft substitutes have been developed to provide osteoconductive matrices as well as to enhance osteoinductivity. A tricalcium phosphate and glutaraldehyde crosslinked gelatin (GTG) scaffold, incorporated with bone morphogenetic proteins (BMPs), was developed to provide an alternative mean of bone tissue engineering. This study investigated differences between GTG and BMP-4 immobilized GTG (GTG-BMP) scaffolds on neonatal rat calvaria osteoblast activities. The GTG scaffold possessed an average pore size of 200 microm and a porosity of 75%. HE staining revealed uniform cell distribution throughout the scaffold 24 h post cell seeding. Alkaline phosphatase (ALP) activity of the GTG samples increased initially and then stabilized at 3 weeks postseeding. ALP activity of the GTG-BMP samples was similar to that of the GTG samples in the second and third weeks, but it continued increasing and became significantly greater than that of the GTG samples by the fourth week. Gla-type osteocalcin (Gla-OC) activity of the GTG-BMP samples was initially lower, but also became significantly greater than that of the GTG samples by the fourth week. An HE stain revealed greater numbers of attached cells and a richer matrix deposits in the GTG-BMP samples. A von Kossa stain showed larger mineralizing nodules, in greater numbers, after 4 weeks of in vitro cultivation. These findings suggest that the GTG scaffold provides an excellent porous structure, conductive to greater cell attachment and osteoblast differentiation, and that utility can be significantly enhanced by the inclusion of BMPs. A GTG-BMP scaffold holds promise as a superior bioactive material for bone tissue engineering.

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