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Biomedical subjects

N Ashammakhi

Publications and source records attributed to N Ashammakhi.

At least 19 recordsLinked to original sources

Novel drug delivery systems in pain therapy.

Pain is an unpleasant sensory experience resulting from damage to bodily tissues. It is considered a significant public health problem because it affects 1/5 of the world population and causes loss of great amounts of money. Pain reflects a mixture of pathological, psychological and genetic conditions that need deep understanding to be efficiently treated. If under-treated, pain results in serious immune and metabolic problems. Pain management faces many problems that limit its control. For instance, efficiency of pain killers is limited, pain killers give rise to serious side effects and inability of drug administration methods to help in pain control. Technology can overcome some of these problems and the introduction of implantable controlled drug delivery systems (CDDS), manufactured from biodegradable materials, offers a solution. Implantable CDDS provide good level of pain control, as they continuously provide drug, reduce side effects and improve patients' compliance. Biodegradable type of implantable CDDS are polymer based devices that are fabricated to locally deliver drugs in a pre-designed manner. They are currently a focus of research in the field of pain therapy in order to explore their chance to offer an alternative to the conventional methods for drug delivery. This paper aims to highlight the dimensions of pain issue and to overview the basics of drug release from polymers used for CDDS in pain management. In addition, it discusses the recent advances in the technologically designed drug delivery systems in the field of pain medicine and their clinical applications. Future perspectives are also presented.

Analgesics↗

Autologous blood transfusion following total knee arthroplasty: is it always necessary?

A retrospective study of 85 patients undergoing primary total knee replacement (TKR), who also received autologous blood transfusion (ABT) to compensate for the perioperative blood loss. In our series 16.4% of the patients needed allogenic blood transfusion. Of the remaining 83.4% only 49.5% received autologous transfusion. Autologous transfusion was withheld in 34.1% of cases either because the blood volume was inadequate or because the collection time exceeded the recommended time limit. The mean haemoglobin (Hb) level with or without autologous transfusion was 10 g, raising the question of the necessity of using autologous transfusion in primary total TKR.

Arthroplasty, Replacement, Knee↗

Innovation in multifunctional bioabsorbable osteoconductive drug-releasing hard tissue fixation devices.

We review in this paper the work performed by our group to develop multifunctional bioabsorbable ciprofloxacin releasing bone implants. Poly lactide-co-glycolide (PLGA 80/20 and polylactide (P(L/DL)LA 70/30) were used. Ciprofloxacin (CF) and bioactive glass (BaG) 13-93 were added. The mixture was then extruded and self-reinforced. CF release, mechanical strength, and the effect on S. epidermidis attachment and biofilm formation were evaluated. In rabbits, tissue reactions were assessed. Pull out strength was evaluated in cadaver bones. CF was released over 44 weeks (P(L/DL)LA) and 23-26 weeks (PLGA). Initial shear strength of the CF screws was 152 MPa (P(L/DL)LA) and 172 MPa (PLGA). Strength was retained for 12 weeks (P(L/DL)LA) and 9 weeks (PLGA). Histologically, CF releasing implants did not show much difference from control plain PLGA screws except for increased giant cells. CF miniscrews had lower pullout strength than the controls, but CF tacks had better values than controls. BaG led to a drop in pullout strength properties. Bacterial growth, attachment and biofilm formation on CF implants was significantly reduced when compared to controls. Accordingly, bioabsorbable multifunctional implants with appropriate CF release, mechanical, and biocompatibility properties are possible to develop and are considered appropriate to apply clinically.

Absorbable Implants↗

Histomorphometric analysis of poly-L/D-lactide 96/4 sutures in the gastrocnemius tendon of rabbits.

BACKGROUND: Common Achilles tendon ruptures are not usually fixed by bioabsorbable sutures due to limitations in their strength retention properties. Modern technology has made it possible to develop bioabsorbable sutures with prolonged strength retention. AIMS: To evaluate histologically tissue reactions of poly-L/D-lactide (PLDLA) sutures implanted in Achilles tendon of rabbits. MATERIAL AND METHODS: Fifteen rabbits were evaluated at 2, 6 and 12 weeks postoperatively, with five rabbits in each follow-up group. PLDLA monofilament sutures were implanted into the medial gastrocnemius tendon. Polyglyconate monofilament sutures with similar diameter (Maxon 4-0, Cyanamid of Great Britain Ltd., Gosport, UK) were implanted in the contralateral gastrocnemius tendon. The histology was studied in hard-resin embedded samples. The thickness of the formed fibrous tissue capsule was determined histomorphometrically. RESULTS: PLDLA led to formation of significantly thinner fibrous tissue capsule than Maxon sutures of the same diameter. Median thickness (PLDLA vs. Maxon) at two weeks was 5.26 vs.13.22 microm, at six weeks 11.66 vs. 80.97 microm, and at 12 weeks 10.63 vs. 17.59 microm (p<0.01). CONCLUSIONS: During the 12 week follow-up period, PLDLA sutures implanted intratendineously formed thinner fibrous capsule than Maxon sutures of the same diameter. The suture materials were not totally absorbed by 12 weeks.

Animals↗

A novel bioabsorbable composite membrane of Polyactive 70/30 and bioactive glass number 13--93 in repair of experimental maxillary alveolar cleft defects.

A novel bioabsorbable composite membrane of polyethylene oxide terephthalate and polybutylene terephthalate copolymer (Polyactive 70/30) combined with bioactive glass No. 13--93 was tested in the repair of experimental maxillary alveolar cleft defects. In this pilot study, the possible ability of the membrane to promote bone formation by guided tissue regeneration was investigated. Standard alveolar defects were made bilaterally in the maxilla of 12 growing rabbits and were filled with autogenous bone grafts. The test defect was covered with the composite membrane and the other defect was left uncovered to serve as a control. The follow-up time was 10 weeks. Radiological, histological, and histomorphometric evaluations were performed. Radiologically, no statistically significant differences between test and control defects at 10 weeks were found. Histologically, the membrane enhanced osteogenic activity locally at the membrane-bone interface. Swelling of the membrane was observed. Histomorphometrically, no significant promotion of bone formation by the membrane was observed. The composite membrane was found to be biocompatible and surgically easy to use, but its osteopromotive effect was limited in this experimental cleft model. Further studies are necessary to assess its suitability for reconstructive surgical applications.

Alveolar Process↗

Tyrosine derived polycarbonate membrane is useful for guided bone regeneration in rabbit mandibular defects.

Standardized bilateral through-and-through defects (12x6 mm) were created extraorally in the mandibular angle of 18 New Zealand White rabbits. Animals were divided in to three groups (n=6) according to the intended healing time. On the left side, defects were covered with a poly(desaminotyrosyl-tyrosine-ethyl ester carbonate) (PDTE carbonate) membrane wrapped around the inferior border of the mandible and fixed with bioabsorbable sutures. On the right side, the defects were filled with a mesh made of bioactive glass 13-93 and 3 wt% chitosan. The defects were covered with the same membranes. Periosteal flap was sutured over the membrane. Radiographically, bone ingrowth was seen in all specimens at 12 weeks postoperatively. At 24 weeks, completely ossified area remained approximately at the same level as at 12 weeks, but the non-ossified area decreased to almost zero. However, the bioactive glass mesh did not improve the results. Nevertheless, enveloping the defect with PDTE carbonate membrane seemed to play a crucial role in new bone formation. Based on these results, we conclude that tyrosine polycarbonate is a promising new material for guided bone regeneration.

Animals↗

Effect of human platelet supernatant on proliferation and matrix synthesis of human articular chondrocytes in monolayer and three-dimensional alginate cultures.

Articular cartilage is rich in collagen type II fibres and proteoglycans and is characterized by low cell density. Chondrocytes have specific nutritional requirements and therefore cannot be expanded in vitro without the risk of generating fibroblastoid cells expressing type I collagen. Therefore, various growth conditions were tested for cartilage tissue engineering. Human platelets are a rich source of many growth factors including transforming growth factor-beta and platelet-derived growth factor. To investigate the effect of human platelet supernatant (hPS) on chondrocyte proliferation and differentiation, human articular biopsies obtained from three healthy donors. Chondrocytes were isolated and expanded separately in monolayer cultures and seeded in alginate beads in the presence and absence of hPS of 1% or 10% v/v concentration. Transcript levels of genes encoding chondrogenic factors were determined by quantitative reverse transcriptase-polymerase chain reaction. The deposition of types I and II collagen as well as proteoglycan was detected by indirect immunocytochemistry. Addition of hPS activated chondrocyte proliferation in monolayer cultures but induced a dedifferentiation of chondrocytes towards a fibroblast-like phenotype. The expression levels of mRNAs encoding type II collagen, aggrecan and bone morphogenetic protein-2 were reduced in all samples tested. Seeding chondrocytes in alginate beads in the presence of hPS generated a cell population capable of type II collagen expression, even though hPS induced considerable type I collagen expression as well. Differences (1% vs. 10% group, 1% vs. control, 10% vs. control) in the quantitative gene expression of types I and II collagen or of aggrecan were statistically significant (p<0.001). We conclude that addition of hPS may accelerate chondrocyte expansion but can lead to their dedifferentiation.

Adult↗

Recurrent aphthous ulcers today: a review of the growing knowledge.

Recurrent aphthous ulcers represent a very common but poorly understood mucosal disorder. They occur in men and women of all ages, races and geographic regions. It is estimated that at least 1 in 5 individuals has at least once been afflicted with aphthous ulcers. The condition is classified as minor, major, and herpetiform on the basis of ulcer size and number. Attacks may be precipitated by local trauma, stress, food intake, drugs, hormonal changes and vitamin and trace element deficiencies. Local and systemic conditions, and genetic, immunological and microbial factors all may play a role in the pathogenesis of recurrent aphthous ulceration (RAU). However, to date, no principal cause has been discovered. Since the aetiology is unknown, diagnosis is entirely based on history and clinical criteria and no laboratory procedures exist to confirm the diagnosis. Although RAU may be a marker of an underlying systemic illness such as coeliac disease, or may present as one of the features of Behcet's disease, in most cases no additional body systems are affected, and patients remain otherwise fit and well. Different aetiologies and mechanisms might be operative in the aetiopathogenesis of aphthous ulceration, but pain, recurrence, self-limitation of the condition, and destruction of the epithelium seem to be the ultimate outcomes. There is no curative therapy to prevent the recurrence of ulcers, and all available treatment modalities can only reduce the frequency or severity of the lesions.

Adolescent↗

Management of Gartland's type III supracondylar fractures of the humerus in children: the role audit and practice guidelines.

In 1995, we audited the outcome following Gartland's type III supracondylar fractures of the humerus in children. Closed reduction under anaesthesia (MUA) and cast immobilisation was the treatment of choice, with the treatment changed whenever displacement occurred. The result of the audit showed that 86% of cases were treated with this method. The rate of re-operation was 45.6%. Cubitus varus deformity developed in 50% of cases. Guidelines were introduced in order to abandon the use of MUA and cast immobilisation for type III fractures. The guidelines recommended treating these fractures with rigid fixation using Kirchner (K) wires. A re-audit was conducted in the year 2000 to study the impact of introducing the guidelines. The rate of compliance was 64%. The re-audit showed a significant drop in the rate of re-operations from 45.6 to 17.7% (P = 0.0043), and a significant drop in the incidence of cubitus varus from 50 to 6.6% ( P < 0.0001). The results of the re-audit suggest that practice guidelines can have a major impact on clinical practice.

Bone Wires↗

Use of bioabsorbable osteofixation devices in the hand.

Bioabsorbable internal fixation by means of pins, tacks, screws and miniplates offers an alternative to metallic osteofixation for the stabilization of small bone fractures, osteotomies, ligament injuries and fusions in the hand. The advantages of using them include avoidance of metallic-implant-related long-term complications and a secondary removal operation. Currently the most commonly used devices are made of poly L-lactide (PLLA) and copolymers of polylactides (P(L/DL)LA) and polyglycolide (PLGA). In areas of mechanical stress, the use of ultra-high-strength self-reinforced devices is recommended. Biomechanical studies on fresh frozen bones have shown that the fixation rigidity achieved with self-reinforced devices approaches that of metallic osteofixation methods. The reliability of modern implants has been confirmed in several experimental and clinical studies.

Absorbable Implants↗

Treatment of pectus excavatum with bioabsorbable polylactide plates: Preliminary results.

BACKGROUND/PURPOSE: Pectus excavatum usually is corrected by thoracoplasty using metal plates. Recently bioabsorbabe polylactide plates have been developed. The aim of this study was to compare outcome after use of metal and bioasorbable plates in thoracoplasty performed for correction of pectus excavatum. METHODS: Eighty-three children (<16 years old) underwent thoracoplasty (Sulamaa's technique). In 75 patients, metallic plates, and in 8 patients, self-reinforced poly-L-lactide (SR-PLLA) plates, were used. Seven patients in the SR-PLLA group and 13 patients in the metal plate group were assessed 0.5 to 13 years postoperatively. RESULTS: The mean operating time was 121 minutes in the metal plate group, and 87 minutes in the SR-PLLA plate group. In the metal plate group, complications were pain caused by instability of the metal plates (n = 17), wound infection (n = 3), recurrence of deformity (n = 3), postoperative pain (n = 3), pneumothorax (n = 1), and nonspecific postoperative fever (n = 1). Thirteen patients underwent reoperation to refix the position of the metallic plates. In the SR-PLLA group, one case of pneumothorax occurred, and plate fragment palpability caused local pain in one patient. Cosmetic results and lung function values were similar. CONCLUSION: Our preliminary results show that bioabsorbable plates are a useful option in the treatment of pectus excavatum in children.

Absorbable Implants↗

Comparison of strength properties of poly-L/D-lactide (PLDLA) 96/4 and polyglyconate (Maxon) sutures: in vitro, in the subcutis, and in the achilles tendon of rabbits.

Achilles tendon rupture is a common injury. Absorbable sutures are not commonly used because of their limited strength properties. Recently, sutures with prolonged strength retention properties have been developed. The aim of the study is to test the mechanical properties of recently developed poly-L/D-lactide (PLDLA) sutures in comparison with polyglyconate (Maxon) sutures. PLDLA (0.2 mm thick) and Maxon (4.0) sutures were studied in vitro by immersion in a buffered saline solution (pH 7.4). Tensile strength tests were done on sutures retrieved after 1-26 weeks. In vivo, they were implanted in the subcutis of 32 rabbits. Tensile strength tests were done on sutures retrieved after 1-6 weeks. The sutures were also used to repair the Achilles tendon in rabbits. Maximum force before breaking and percentage elongation of tendons were determined. Although PLDLA had a lower initial tensile strength than Maxon, PLDLA showed more prolonged tensile strength retention than Maxon. Tendons repaired with PLDLA, however, had a lower strength than Maxon-repaired tendons at six weeks (insignificant difference). PLDLA has more prolonged tensile strength properties compared with Maxon. Thus, PLDLA offers an alternative to Maxon in repair of the Achilles tendon.

Absorbable Implants↗

[Reconstruction of the lower urinary tract. Developments at the beginning of a new century].

Gastrointestinal segments are currently by far the most popular method to create a bladder substitute. Attempts have been made to further reduce the morbidity and burden for patients by using minimal invasive techniques for both cystectomy and urinary diversion. However, laparoscopy for acceptable forms of urinary diversion is time consuming and costly. A neobladder "off the shelf" would be a better solution. Tissue engineering is an exciting new field which enables the cultivation and expansion of individual bladder cells obtained by transurethral biopsy, the attachment of these cells to a support matrix, and their reimplantation into the body. Advances both in biomaterials as well as in the cultivation and expansion of bladder cells are described. Promising routine clinical applications of tissue engineering may still need several years. Free neurovascular muscle transfer to the bladder demonstrated both experimentally and clinically to be a suitable treatment modality in patients with bladder acontractility. This may therefore be the next logical step towards an improved bladder substitute by combining well vascularized flaps with urothelial cell seeding. Thus a combination of commonly used flap techniques and tissue engineering may soon be possible.

Forecasting↗

Developments in craniomaxillofacial surgery: use of self-reinforced bioabsorbable osteofixation devices.

Because of the problems associated with the conventional osteofixation devices used in craniomaxillofacial surgery, absorbable devices present an appealing alternative. Devices made of the polymers polylactide, polyglycolide, and their copolymers (PLGA and P[L/DL]LA) are currently the most commonly used. Ultrahigh-strength implants can be manufactured from these polymers with the self-reinforcing technique. Over the authors' almost two decades of study, both in experimental and clinical settings, self-reinforced devices have proved to be biocompatible, easy to handle, and mechanically strong, even for the fixation of femoral neck fractures. In craniomaxillofacial surgery, the authors have used self-reinforced devices for over 8 years without complications. Because of the more favored degradation characteristics, currently the copolymeric self-reinforced devices (P[L/DL]LA, Biosorb FX and PLGA, Biosorb PDX; Elite Performance Technologies, Solana Beach, Calif.) represent the advancing front in the application of absorbable devices in craniomaxillofacial surgery. The authors' share their experience and their studies of self-reinforced devices, which possess the highest strength and ductility of all bioabsorbable products.

Absorbable Implants↗

A new technique for correction of trigonocephaly in an infant: application of an absorbable endocranial plate.

We report on a new method of cranial bone osteofixation using absorbable material, which is applied endocranially to avoid the application of a thick, cosmetically inferior system epicranially in the frontal area. This is especially important in the correction of deformity in trigonocephaly cases. A 9-month-old boy presented with a prominent trigonocephalic deformity. Cranioplasty was performed, in which a supraorbital bar (bandeau) was removed, reinforced with a self-reinforced polylactide (SR-PLA) plate and reshaped to correct the deformity. The plate was applied on the inner side of the bony bar, with its ends fixed epicranially to the temporal bones by means of SR-PLA miniscrews. 3-D CT scans and rapid prototypes were used to evaluate the results. Stable and secure fixation was obtained, and the cosmetic result appeared excellent. No complications occurred during the postoperative period of 1 year. Hence, stabilisation of cranial bone can be achieved endocranially using an absorbable plate and screws, with an encouraging cosmetic result. The method is thought to be reliable.

Biocompatible Materials↗

Bioabsorbable scaffolds for guided bone regeneration and generation.

Several different bioabsorbable scaffolds designed and manufactured for guided bone regeneration and generation have been developed. In order to enhance the bioactivity and potential osteoconductivity of the scaffolds, different bioabsorbable polymers, composites of polymer and bioactive glass, and textured surface structures of the manufactured devices and composites were investigated in in vitro studies and experimental animal models. Solid, self-reinforced polyglycolide (SR-PGA) rods and self-reinforced poly L-lactide (SR-PLLA) rods were successfully used as scaffolds for bone formation in muscle by free tibial periosteal grafts in animal experiments. In an experimental maxillary cleft model, a bioabsorbable composite membrane of epsilon-caprolactone and L-lactic acid 50/50 copolymer (PCL/LLA) film and mesh and poly 96L,4D-lactide (PLA96) mesh were found to be suitable materials for guiding bone regeneration in the cleft defect area. The idea of solid layer and porous layer combined together was also transferred to stiff composite of poly 70L,30DL-lactide (PLA70) plate and PLA96 mesh which structure is introduced. The osteoconductivity of several different biodegradable composites of polymers and bioactive glass (BG) was shown by apatite formation in vitro. Three composites studied were self-reinforced composite of PLA70 and bioactive glass (SR-(PLA70 + BG)), SR-PLA70 plate coated with BG spheres, and Polyactive with BG.

Animals↗