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Preparation of porous biodegradable poly(lactide-co-glycolide)/ hyaluronic acid blend scaffolds: characterization, in vitro cells culture and degradation behaviors.

A series of poly(lactide-co-glycolide) (PLGA)/ hyaluronic acid (HA) blend with different HA composition were used to fabricate scaffolds successfully. The pores of the three dimensional scaffold were prepared by particle leaching and freeze drying. The pore size was about 50-200 microm and the porosity was about 85%. The characterizations of the scaffold, such as mechanical properties, hydrophilicity and surface morphologies were determined. Mouse 3T3 fibroblast was directly seeded on the scaffolds. The cell adhesion efficiency, cell morphology observed by scanning electron microscopy (SEM) and the degradation behavior of the blend scaffold were evaluated. In summary, the results show that the adhesion efficiency of cells on the PLGA/HA blend scaffold is higher than that on the PLGA scaffold. Moreover, the incorporation of HA in PLGA not only helps to increase the cell affinity but also tends to lead the water and nutrient into the scaffold easily.

3T3 Cells↗

Material and knot properties of braided polyester (Ticron) and bioabsorbable poly-L/D-lactide (PLDLA) 96/4 sutures.

The purpose of the present study was to investigate in vitro the biomechanical material and knot properties and histomorphometrical knot properties of 3-0 braided polyester suture (Ticron) and bioabsorbable poly-L/D-lactide (PLDLA) 96/4 suture. In Ticron five throws are needed to form a secure knot, and the 1 = 1 = 1 = 1 = 1 and the 2 = 1 = 1 = 1 configurations are recommended. For PLDLA several granny and square knots formed a secure knot, but the 1 = 1 and 1 = 1 = 1 knots were the best. These PLDLA knots had lower yield force and strain at yield point, but higher stiffness than the recommended Ticron knots. The ultimate force values did not differ, but PLDLA knots had significantly higher strain at ultimate point. In the histomorphometrical analysis of the recommended knots, the PLDLA knots had a significantly smaller knot surface area than the Ticron knots. According to these results, PLDLA suture proved to be suitable for flexor tendon repair.

Absorbable Implants↗

The effects of types of degradable polymers on porcine chondrocyte adhesion, proliferation and gene expression.

Understanding how a specific biomaterial may influence chondrocyte adhesion, proliferation and gene expression is important in cartilage tissue engineering. In this study several biodegradable polymers that are commonly used in tissue engineering were evaluated with respect to their influence on chondrocyte attachment, proliferation and gene expression. Primary cultures of porcine chondrocytes were performed in films made of poly-L-lactic acid (PLLA), poly-D,L-lactic acid (PDLLA), poly-(lactide-co-glycolide) (PLGA), or polycaprolactone (PCL). Chondrocytes adhered to PDLLA or PLGA after 1-day incubation better than to PLLA or PCL. After 7 or 14 day culture, the cell numbers on PDLLA or PLGA was still higher than PLLA or PCL. The results suggested that cell attachment and growth might depend on degradation rate of biodegradable polymers. Along with the fact that PDLLA or PLGA supported expression of chondrocyte specific genes more than PLLA or PCL, the former two materials seemed to be more suitable for cartilage tissue engineering than the latter ones. Besides, we found that chondrocyte phenotype prior to seeding was important in the expression of ECM proteins.

Absorbable Implants↗

Regeneration of the rat spinal cord after thoracic segmentectomy: restoration of the anatomical integrity of the spinal cord.

Segmentectomy of the spinal cord (SC) was performed in 28 rats at the level of the tenth thoracic vertebra. Scar formation at the operation site was studied, along with the completeness of the anatomical integrity of the SC, in control animals (group 1) and after filling of the defect with the neural matrix Spherogel (group 2) and with Spherogel containing embryonic nerve cells (group 3). The defect in the SC in animals of the control group was filled with fibrin masses by 1-2 weeks, while connective tissues scars were already formed by this time in rats of experimental groups 2 and 3. By 10-11 weeks, these animals showed partial recovery of movement in the three lower limb joints. The scar tissue and adjacent zones of the SC showed large quantities of regenerating fine myelinated nerve fibers. These were clearly evident in the zones of the cranial and caudal margins, to the extent of the appearance of typical SC tissue. In preparations obtained from control animals, fine myelinated fibers were noted in the immediate vicinity of SC substance, while nerve fibers were few in number in scar tissue and the cellular bands of the transitional zone.

Absorbable Implants↗

Fibrin glue and bioabsorbable felt patch for intraoperative intractable air leaks.

OBJECTIVE: We worked to devise a new way to prevent postoperative persistent air leaks in high-risk pulmonary surgery patients. METHODS: From November 1993 to June 2002, 60 patients with difficult to control intraoperative pulmonary air leakage were treated using bioabsorbable polyglycolide felt patches soaked in fibrin glue to cover the leakage site. RESULTS: After application, the felt patch adhered tightly to the lung surface without peeling off, enabling good leakage closure with only 2 ml of fibrin glue used. Air leakage was controlled successfully in 52 (86.7%) of the 60. Four of the 8 patients in whom this method failed to stop air leakage also developed mild pyothorax, with 2 requiring a second operation by video-assisted thoracic surgery. Leakage was eventually controlled in all patients, with no postoperative deaths relating to air leakage. CONCLUSIONS: Fibrin-glue-soaked bioabsorbable felt patches effectively seal intraoperative intractable air leaks. Felt patch use may increase the risk of postoperative infection. It should be considered for use on patients with fistulas that cannot be controlled by direct closure or otherwise intraoperatively and who may potentially develop uncontrollable air leakage postoperatively.

Absorbable Implants↗

Plastic surgical approaches for HIV-associated lipoatrophy.

Prolonged antiretroviral therapy, particularly with thymidine analogue-based regimens, may lead to generalized lipoatrophy. The facial changes associated with lipoatrophy are highly stigmatizing, affecting quality of life and decisions around therapy. Changes in antiretrovirals to thymindine-sparing regimens may lead to gradual fat recovery but, even over several years, may not result in impressive restoration of appearance. The need for a rapid and effective panacea for facial changes has led to investigation of a range of cosmetic treatments to enhance facial appearance. Surgical fillers, which may be either permanent or biodegradable, are the mainstay of cosmetic management. These treatments not only lead to improved physical appearance but also may reduce social anxiety and depression.

Absorbable Implants↗

In vitro degradation behavior of a novel bioresorbable composite material based on PLA and a soluble CaP glass.

Poly(alpha-hydroxy acids), and in particular polylactic acid (PLA), are nowadays amongst the most used bioabsorbable materials. However, this polymer may not meet some application requirements due to inadequate mechanical properties and or its degradation characteristics. A possible strategy to tackle this problem is the incorporation of an inorganic phase into the polymeric matrix. In this work a new fully biodegradable composite material made with PLA and calcium phosphate soluble glass particles has been developed. The behaviour of the PLA/glass composite has been analysed during its degradation in simulated physiological conditions by means of weight loss, molecular weight and thermal properties analysis and electron microscopy observation. The results showed that the incorporation of phosphate glass particles into the polymer significantly accelerated the degradation of the PLA and induced the formation of calcium phosphate precipitates at the composite surface.

Absorbable Implants↗

Effect of iron on the surface, degradation and ion release properties of phosphate-based glass fibres.

Phosphate-based glass fibres (PGF) have the unique characteristic of being completely soluble in an aqueous environment, releasing bioactive and biocompatible ions. They have been proposed as tissue engineering scaffolds for craniofacial skeletal muscle regeneration, where myoblasts are seeded directly onto the fibres. Studies have shown that these cells have a preference in their initial attachment to fibres of certain composition and size, which in turn control the rate of degradation. This study investigated the relationship between the surface properties, degradation properties and ion release (cationic and anionic species) by altering the chemical composition of the PGF. Iron oxide (Fe2O3) was incorporated into glasses containing P2O5 (50 mol%), CaO (30 mol%) and Na2O (20 mol%). Six glass compositions with Fe2O3 ranging from 0 to 5 mol% by replacing the equivalent Na2O mol% were investigated. Contact angle measurements showed that polar interactions occurring on the glass surfaces diminished with increasing Fe2O3 content. This behaviour was reflected in the estimated surface energies of the glasses, where the overall surface energy decreased with increasing Fe2O3 content due to the decrease in polar or acid/base component. The incorporation of up to 5 mol% Fe2O3 into PGF resulted in a significant reduction in the degradation rate (by two orders of magnitude), which can be related to the formation of more hydration resistant P-O-Fe bonds. However, the degradation rate increased with decreasing fibre diameter (comparing average diameters of 31.6 +/- 6.5 microm versus 13.1 +/- 1.3 microm) for a given mass of fibre, and this is related to the surface area to volume ratio. Taken together the results suggest that fibres with the larger diameters and containing 3-5 mol% Fe2O3 could initially be a more durable scaffold than ones with 1 or 2 mol% Fe2O3 for initial cell attachment.

Absorbable Implants↗

Biodegradable HA-PLA 3-D porous scaffolds: effect of nano-sized filler content on scaffold properties.

Scaffolds comprising poly(lactic acid) and nano-hydroxyapatite (HA) were prepared using the solvent-casting/salt-leaching technique. NaCl was used as the leaching agent. Nano-sized HA was synthesized by a hydrothermal method at 170 degrees C and autogenous pressure. High-resolution TEM imaging revealed that the HA particles were ellipsoidal-shaped with needle-like morphologies. The particles had an average size of approximately 25 nm in width and 150 nm in length with aspect ratios ranging from 6 to 8. As the HA content increased in the scaffold from 0 to 50 wt%, the compression modulus of the scaffolds increased from 4.72+/-1.2 to 9.87+/-1.8 MPa, while the yield strength from 0.29+/-0.03 to 0.44+/-0.01 MPa. Such polymeric scaffolds should be suitable materials for non-load sharing tissue-engineering applications.

Absorbable Implants↗

Dexamethasone loaded bioresorbable films used in medical support devices: structure, degradation, crystallinity and drug release.

Bioresorbable polymer films containing dexamethasone (DM) were prepared using a solution processing technique. Investigation of the films focused on cumulative DM release as affected by film morphology (drug location/dispersion in the film) and degradation processes. Two film structures were studied: A-type, a polymer film with large drug crystals located on the film's surface, and B-type, a polymer film with small drug particles and crystals distributed within the bulk. The effect of the polymer's degree of crystallinity on the drug release profile was also studied. Prototypical applications of these films are biodegradable medical support devices which combine mechanical support with drug release. In most of our studied systems the drug release profile from the film is determined mainly by both drug location/dispersion in the film and the polymer's weight loss rate. All release profiles from A-type films exhibited a burst effect of approximately 30%, accompanied by a second release phase at a constant rate, whereas the release profiles from B-type films were determined mainly by the degradation profile of the host polymer, and did not exhibit any burst effect. A high degree of crystallinity is important for the current application, since good mechanical properties are required. This contributes to slower drug release rates, mainly at relatively low weight losses, whereas at high weight losses, where a porous structure is created, the crystallinity almost does not affect the rate of drug release. The shape of the porous structure that develops with degradation also affects the drug release profile from the B-type films.

Absorbable Implants↗

Synthesis and characterization of novel biotinylated biodegradable poly(ethylene glycol)-b-poly(carbonate-lactic acid) copolymers.

Poly(ethylene glycol)-b-poly(5-benzyloxy-trimethylene carbonate-lactic acid) copolymers (PEG-b-P(BTMC-LA)) were synthesized by ring-opening polymerization of lactide and 5-benzyloxy trimethylene carbonate in the presence of mono-hydroxyl poly(ethylene glycol) with diethyl zinc as catalyst. They were further converted into deprotected copolymers with the pendant hydroxyl groups by hydrogenolysis in the presence of Pd(OH)2/C, and finally conjugated with biotin through the free hydroxyl groups. Gel permeation chromatography, Fourier transform infrared, differential scanning calorimetry and 1H nuclear magnetic resonance studies confirmed the copolymer structures and successful attachment of biotin to the copolymer.

Absorbable Implants↗

Collagen gel systems for sustained delivery and tissue engineering.

Collagen gels are flowable, suggesting the possibility of an easily injectable, biocompatible drug delivery matrix. Sustained release of therapeutic molecules from collagen matrices, however, is beset with difficulties. Fibrillar collagen gels have an effective pore size of several tens of nanometers, too large to control release by hindered diffusion. To control release, it is necessary to rely on binding of the active agent to collagen, either by covalent or non-covalent bonds, or on sequestering in a secondary matrix. Such steps rapidly increase the complexity of the system. Non-fibrillar collagen has a lower effective pore size (4-6 nm), but it dissolves rapidly in vivo (approximately 24 h). For tissue engineering applications, collagen gels are more attractive, since they can act as a "cage" to retain cells or as gene delivery complexes, which are larger than drugs and therapeutic proteins. The gels have limitations in terms of strength, but reinforcement with solid components and alignment during gelation and culture can improve performance.

Absorbable Implants↗

Atelocollagen for protein and gene delivery.

Recent progress in recombinant gene technology and cell culture technology has made it possible to use protein and polynucleotides as effective drugs. However, because of their short half-lives in the body and the necessity of delivering to target site, those substances do not always exhibit good potency as expected. Therefore, delivery systems of such drugs are important research subjects in the field of pharmacology, and to prolong the effect of these drugs, many studies are being conducted to control the release of proteins and polynucleotides from various carrier materials. Collagen is one of the most useful carrier materials for this purpose. In this article, we report on the controlled release of protein drugs using collagen, focusing on a new drug delivery system (DDS), the Minipellet, as our basic technology. Then we introduce our recent work about gene therapy using collagen-based DDS. Basic formulation study showed that collagen DDS protects DNA degradation from both chemical cleavage and enzymatic digestion. A single injection of collagen DDS containing plasmid DNA produced physiologically significant levels of gene-encoding proteins in the local site and systemic circulation of animals and resulted in prolonged biological effects. These results suggest that collagen DDS containing plasmid DNA may enhance the clinical potency of plasmid-based gene transfer, facilitating a more effective and long-term use of naked plasmid vectors for gene therapy. Also, variety kinds of application of collagen DDS for gene therapy using adenovirus vector, antisense DNA and DNA vaccine, will be discussed.

Absorbable Implants↗

Global regulatory registration requirements for collagen-based combination products: points to consider.

Collagen-based medical products provide an ideal and unique matrix for the delivery of drugs, biologics and other therapeutic agents. Collagen has a long history of safety and effectiveness. Collagen is biodegradable with minimal tissue reaction. Regulatory requirements for approval of collagen-based combination products are changing as more high technology combinations are developed. There are special considerations that need to be addressed for collagen products. Products of animal origin must meet specific requirements in regards to safety factors regarding Transmissable Spongiform Encephalopathies. Global regulatory registration requirements and special controls are presented.

Absorbable Implants↗

Collagen as a carrier for on-site delivery of antibacterial drugs.

Due to its biocompatibility and well-established safety profile, collagen represents a favourable matrix for on-site drug delivery. In this review, we summarize some of the recent developments and applications of collagen as a biomaterial in drug delivery systems for antibiotics, especially gentamicin. The main clinical and experimental applications covered include: treatment and prophylaxis of bone and soft tissue infections, wound healing, as well as ophthalmic and periodontal treatment. Advantages of local drug application and the rationale of use local drug delivery systems for adjuvant (ancillary) therapy are discussed. Recent efforts in the use of collagen and collagen-synthetic polymer composites for controlled drug delivery as well as collagen-based diffusion membranes for prolonged drug release have also been included in this review.

Absorbable Implants↗

Collagens--major component of the physiological cartilage matrix, major target of cartilage degeneration, major tool in cartilage repair.

Collagens serve important mechanical functions throughout the body and in particular in the connective tissues. Additionally, collagens exert important functions as cellular microenvironment and partly via binding and release of cellular growth mediators. In articular cartilage, fibrillar collagens are providing most of the biomechanical properties of the extracellular matrix essential for its functioning. The collagenous matrix is one main target of destructive processes in general degenerative joint disease and focal matrix lesions. The development of an adequate collagen framework represents the major aim of therapeutic cartilage repair. In this respect, collagenous matrices or collagen-imitating scaffolds are more and more emerging as highly suitable vehicles for cell and (growth) factor transport into cartilage lesion. Thus, collagens are not only major constituents of connective tissues in terms of integrity and function, they are also major targets of tissue destruction and regeneration and might become major tools to achieve tissue repair.

Absorbable Implants↗

Micro and nano-fabrication of biodegradable polymers for drug delivery.

This paper presents state-of-the-art micro and nano-fabrication techniques for biodegradable polymers. Replication molding, using a rigid or elastic master, can pattern structures on a polymer surface in a submicron resolution at a low cost. Layer-by-layer rapid prototyping methods are promising in producing controlled release units with complicated geometries, release mechanisms and the ability to control microstructure and composition. Special attention is paid to the fast, flexible, and non-invasive laser fabrication techniques that have great potential in the fabrication of biodegradable polymer drug delivery devices in both a laboratory and industry scale.

Absorbable Implants↗