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PubMed2006

Collagen scaffolds reinforced with biomimetic composite nano-sized carbonate-substituted hydroxyapatite crystals and shaped by rapid prototyping to contain internal microchannels.

The next generation of tissue engineering scaffolds will be made to accommodate blood vessels and nutrient channels to support cell survival deep in the interior of the scaffolds. To this end, we have developed a method that incorporates microchannels to permit the flow of nutrient-rich media through collagen-based scaffolds. The scaffold matrix comprises nano-sized carbonate-substituted hydroxyapatite (HA) crystals internally precipitated in collagen fibers. The scaffold therefore mimics many of the features found in bone. A biomimetic precipitation technique is used whereby a collagen membrane separates reservoirs of calcium and phosphate solutions. The collision of calcium and phosphate ions diffusing from opposite directions results in the precipitation of mineral within the collagen membrane. Transmission electron microscopy analysis showed the dimension of the mineral crystals to be approximately 180 x 80 x 20 nm, indicating that the crystals reside in the intermicrofibril gaps. Electron diffraction indicated that the mineral was in the HA phase, and infrared spectroscopy confirmed type A carbonate substitution. The collagen-HA membrane is then used to make 3-dimensional (3D) scaffolds: the membrane is shredded and mixed in an aqueous-based collagen dispersion and processed using the critical point drying method. Adjusting the pH of the dispersion to 5.0 before mixing the composite component preserved the nano-sized carbonate-substituted HA crystals. Branching and interconnecting microchannels in the interior of the scaffolds are made with a sacrificial mold manufactured by using a 3D wax printer. The 3D wax printer has been modified to print the mold from biocompatible materials. Appropriately sized microchannels within collagen-HA scaffolds brings us closer to fulfilling the mass transport requirements for osteogenic cells living deep within the scaffold.

Absorbable Implants↗

PubMed1987

[Use of polytetrafluoroethylene (Gore-Tex E-PTFE Soft Tissue Patch) for suspension of former facial paralysis and as reconstructive tissue].

The insertion of autogenous fascia lata to suspend the paralyzed cheek and lips remains one of the most widely practiced procedures in correction of long term paralysis of the lower facial muscles. For 34 months we used thin layers (1 mm) of expanded polytetrafluoroethylene (E-PTFE Gore-Tex Soft Tissue Patch) to replace autogenous fascia lata, in 20 patients, with satisfactory results. 13 patients were treated by classical techniques of insertion-suspensions of the paralyzed side with a perioral loop and slings of PTFE suspended to the zygomatic arch and the infraorbital rim, by way of nasolabial angle or rhytidectomy incisions. In 7 patients, an eyelid suspension was performed with PTFE by Arion's technique, but by replacing the classical silicon thread by E-PTFE and transposing the medial part of the temporalis muscle on the external canthus, and fixing the lateral end of the sling to the muscle. This technique assures a good corneal coverage with healing of the previous ulceration and allows a voluntary occlusion of the eyelids. The PTFE soft tissue is notably successful as an implant. This biocompatible material shows excellent tissue tolerance, the porous microstructure encouraging tissue attachment and infiltration. E-PTFE holds its shape, resists to infection, and permits a notably reduction of the hospitalization because it avoids a second surgical site. We have experience of the material as a reconstructive substance in 6 cases of either bone or subcutaneous deficits, where no other satisfactory solution was available. Is these cases our follow-up is 18 months.

Biocompatible Materials↗

PubMed2005

Poly(dimethylsiloxane) thin films as biocompatible coatings for microfluidic devices: cell culture and flow studies with glial cells.

Oxygen plasma treatment of poly(dimethylsiloxane) (PDMS) thin films produced a hydrophilic surface that was biocompatible and resistant to biofouling in microfluidic studies. Thin film coatings of PDMS were previously developed to provide protection for semiconductor-based microoptical devices from rapid degradation by biofluids. However, the hydrophobic surface of native PDMS induced rapid clogging of microfluidic channels with glial cells. To evaluate the various issues of surface hydrophobicity and chemistry on material biocompatibility, we tested both native and oxidized PDMS (ox-PDMS) coatings as well as bare silicon and hydrophobic alkane and hydrophilic oligoethylene glycol silane monolayer coated under both cell culture and microfluidic studies. For the culture studies, the observed trend was that the hydrophilic surfaces supported cell adhesion and growth, whereas the hydrophobic ones were inhibitive. However, for the fluidic studies, a glass-silicon microfluidic device coated with the hydrophilic ox-PDMS had an unperturbed flow rate over 14 min of operation, whereas the uncoated device suffered a loss in rate of 12%, and the native PDMS coating showed a loss of nearly 40%. Possible protein modification of the surfaces from the culture medium also were examined with adsorbed films of albumin, collagen, and fibrinogen to evaluate their effect on cell adhesion.

Animals↗

PubMed1994

Chitosan-mediated stimulation of macrophage function.

According to the modern definition of biocompatibility, a biocompatible material need not be inert but be bioactive. A benign reactivity implies that the reactivity has to be appropriate for the intended use. Chitosan, a non-acetylated or partially deacetylated chitin (a linear homopolymer of beta (1-4)-linked N-acetylglucosamine) has been proposed as a biomaterial because of its apparent satisfactory biocompatibility. The present investigation demonstrates that chitosan has an in vitro stimulatory effect on both macrophage nitric oxide (NO) production and chemotaxis. The macrophage NO secretion is attributed to the N-acetylglucosamine unit of the chitosan molecule rather than to the glucosamine residue (28 and 15 microM NO respectively). Moreover, the immune stimulatory effect of chitosan was very specific since other glycosaminoglycans, such as N-acetyl-D-mannosamine and N-acetyl-D-galactosamine, had no effects on NO production (5 and 8 respectively). In vivo experiments strengthen this hypothesis. Transmission electron microscopy analysis identifies the presence of many leucocytes in the specimens after 14 d post-implantation, showing poor healing processes (i.e. fibroblast proliferation and collagen deposition) that characterize the tissue repair at this time in our animal model.

Acetylglucosamine↗

PubMed2004

A study of the relationship between mass and physical strength of keratin bars in vivo.

A study was undertaken of the changes in the mass and physical properties of keratin bars implanted subcutaneously in adult rats. A very gradual decrease occurred in vivo in the dry weight of the bars over the period of the study (up to 18 weeks). The elastic modulus of the bars decreased abruptly when present in vivo between 3 and 6 weeks. At the same time there was an increase in the number of cavitations and fissures at the surface of the bars, and an increase in a central internal region of the bars where there was a disorganisation in structure of the polymer. A biocompatible material showing such changes in vivo is likely to be suitable for a variety of medical and surgical applications in which it provides a framework for cell invasion.

Absorbable Implants↗

PubMed2000

In vivo biocompatibility of dextran-based hydrogels.

Dextran-based hydrogels were obtained by polymerization of aqueous solutions of methacrylated dextran (dex-MA) or lactate-hydroxyethyl methacrylate-derivatized dextran (dex-lactate-HEMA). Both nondegradable dex-MA and degradable dex-lactate-HEMA disk-shaped hydrogels, varying in initial water content and degree of substitution (DS, the number of methacrylate groups per 100 glucose units), were implanted subcutaneously in rats. The tissue reaction was evaluated over a period of 6 weeks. The initial foreign-body reaction to the dex-MA hydrogels was characterized by infiltration of granulocytes and macrophages and the formation of fibrin, and exudate, as well as new blood vessels. This reaction depended on the initial water content as well as on the DS of the hydrogel and decreased within 10 days. The mildest tissue response was observed for the gel with the highest water content and intermediate DS. At day 21 all dex-MA hydrogels were surrounded by a fibrous capsule and no toxic effects on the surrounding tissue were found. No signs of degradation were observed. The initial foreign-body reaction to the degradable dex-lactate-HEMA hydrogels was less severe compared with the dex-MA gels. In general, the size of the dex-lactate-HEMA hydrogels increased progressively with time and finally the gels completely dissolved. Degradation of the dex-lactate-HEMA hydrogels was associated with infiltration of macrophages and the formation of giant cells, both of which phagocytosed pieces of the hydrogel. A good correlation between the in vitro and the in vivo degradation time was found. This suggests that extra-cellular degradation is not caused by enzymes but depends only on hydrolysis of the ester and/or carbonate bonds present in the crosslinks of the hydrogels. After 21 days, the degradable hydrogels, as such, could not be retrieved, but accumulation of macrophages and giant cells was observed, both of which contained particles of the gels intracellularly. As for the dex-MA hydrogels, no toxic effects on the surrounding tissue were found. The results presented in this study demonstrate that dextran-based hydrogels can be considered as biocompatible materials, making these hydrogels attractive systems for drug delivery purposes.

Animals↗

PubMed1994

Incus interposition and ossiculoplasty with hydroxyapatite prostheses.

This article traces the evolution of transplant material in ossicular reconstruction of the middle ear. The first transplant consisted of the body and short process of the homograft incus. It was repositioned or wedged between the stapes head and the manubrium of the malleus. Further modification consisted of the sculpture of prostheses from homograft incudes; these were known as the notched incus with short or long process. By means of a notch in the short process, they were locked in place. The final phase is the use of hydroxyapatite as a biocompatible material from which similar prostheses may be precisely manufactured. These hydroxyapatite prostheses, known as the incus and incus-stapes replacement prosthesis, appear to be well tolerated and to produce excellent hearing results.

Biocompatible Materials↗

PubMed1999

An overview of tissue engineered bone.

Numerous important developments in tissue engineering of new bone during the last 10 years are reviewed. Early efforts to combine cells with biocompatible materials are described and applications of this technology are presented with particular focus on uses in orthopaedics and maxillofacial surgery. Basic principles of tissue engineering focusing on cell biology and materials science as used currently in the field are presented. Finally, future challenges are outlined from the perspective of integrating technologies from medicine, biology, and engineering in hopes of translating tissue engineering to clinical applications.

Animals↗

PubMed1998

Tissue engineering: the first decade and beyond.

This article reviews the important developments in the field of tissue engineering over the last 10 years. Research in the area of biomaterials is examined from the perspective of providing the foundation for the development of tissue engineering. Early efforts combining cells with biocompatible materials are described and applications of this technology presented, with particular focus on uses in orthopaedics and maxillofacial surgery. The basic principles of tissue engineering and state-of-the-art technology in cell biology and materials science as used currently in the field are presented. Finally, futures challenges are outlined from the perspective of integrating technologies from medicine, biology, and engineering, in hopes of translating tissue engineering to clinical applications.

Animals↗

PubMed1990

[Histopathologic study on the application of synthetic hydroxyapatite and alpha-tricalcium phosphate for vital pulpotomy].

Hydroxyapatite (HAp) and alpha-Tricalcium phosphate (alpha-TCP) are generally known as materials biocompatible to human tissue. In this study, the adaptation of HAp and alpha-TCP as a pulpotomy agent was studied histopathologically. In this study, HAp granules with a sintering temperature of 1,200 degrees C and sieved through a 37 micron sieve, and APATITE LINER TYPE I (Sankin CO.) as alpha-TCP were used. Calcium hydroxide served as a control. The physical properties of these experimental materials were evaluated and the reaction of pulp tissue to the materials was examined histolongically in dogs. alpha-TCP mixed with saline solution showed more homogeneous and higher viscosity than HAp mixed with saline solution. When alpha-TCP was applied on the site of exposure of a pulp following pulpotomy, the mechanically harmed pulp tissue was healed earlier than when HAp was applied. A hard tissue was formed earliest when calcium hydroxide was used, and then in the order of alpha-TCP and HAp. When HAp was applied, osteodentin was formed and when alpha-TCP was applied, dentin was formed on the site of exposure of a pulp following pulpotomy. When HAp or alpha-TCP was applied, the calcification in the initial stage was not observed. The calcification in initial stage was observed when calcium hydroxide was applied. These results suggest that alpha-TCP is useful as a pulpotomy agent.

Animals↗

PubMed2001

Islet immunoisolation: experience with biopolymers.

Incidence of Type I diabetes is increasing globally and has become a major health concern. There is enough evidence suggesting involvement of autoimmunity in destruction of insulin-producing islets of langerhans which leads to impaired glucose homeostasis. Islet transplantation is one of the approaches that received wide attention. Due to the autoimmune nature of the disease. strategies to protect transplanted islet graft from rejection are sought. Immunoisolation of islets inside semipermeable biocompatible materials is amongst them. Natural biopolymers have been used extensively as immunoisolation materials due to their satisfactory biocompatiblity and tissue tolerance. Here we attempt to address the need for islet immunoisolation and our experience in using natural biopolymers such as chitosan, cellulose and alginate for this application.

Alginates↗

PubMed2003

In vivo behavior of poly(1,3-trimethylene carbonate) and copolymers of 1,3-trimethylene carbonate with D,L-lactide or epsilon-caprolactone: Degradation and tissue response.

The degradation and the tissue response evoked by poly(1,3-trimethylene carbonate) [poly(TMC)] and copolymers of TMC with either 52 mol % D,L-lactide (DLLA) or 89 mol % epsilon-caprolactone (CL) were evaluated in vivo by subcutaneous implantation of polymer films in rats for periods up to one year. Poly(TMC) specimens were extensively degraded after 3 weeks and, as confirmed by histology, totally resorbed in less than a year. A fast linear decrease in thickness and mass without a change in molecular weight was observed. Initially an acute sterile inflammatory tissue reaction, caused by the implantation procedure, was observed, followed by a mild macrophage-mediated foreign body reaction that lasted during the resorption period of the polymer. It is concluded that in vivo, poly(TMC) is degraded via surface erosion involving cellular-mediated processes. The degradation of the copolymers was slower than that of poly(TMC), taking place via autocatalyzed bulk hydrolysis, preferentially of ester bonds. The TMC-DLLA copolymer degraded 20 times faster than the TMC-CL one. In both cases, the tissue reaction upon implantation resembled a sterile inflammatory reaction followed by a foreign body reaction that led to the polymer encapsulation. Significant mass loss was only observed for the TMC-DLLA copolymer, which underwent 96% mass loss in 1 year. When extensive mass loss started, a mild-to-moderate secondary foreign body reaction, related to clearance of the polymer fragments, was triggered. The results presented in this study demonstrate that poly(TMC) and both TMC copolymers are biodegradable and biocompatible materials, making these polymers attractive for the preparation of short- and long-term degradable devices for soft tissue engineering.

Animals↗

PubMed1991

A physical study of vibrating membranes in developing a middle ear prosthesis.

We present a prosthesis meant to replace the tympano-ossicular set as well as the measuring apparatus for developing and characterizing this prosthesis. Such biocompatible materials as silicone elastomer and Teflon are used. Effects due to aging and sterilization have been negligible. Comparisons with anatomic specimens have yielded good results. Furthermore, the first clinical trials with this prosthesis have been promising.

Biocompatible Materials↗

PubMed1995

Heparin bonding of bypass circuits reduces cytokine release during cardiopulmonary bypass.

BACKGROUND: Heparin bonding of the cardiopulmonary bypass (CPB) pump circuit decreases complement activation and fibrinolysis. It is not known whether inflammatory cytokines produced during CPB can also be modulated by the more biocompatible heparin-coated circuit. METHODS: This initial study evaluated the impact of heparin-bonded CPB circuits on production of the cytokines interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-a), IL-6, and IL-8 in adults undergoing complex cardiac operations with prolonged CPB. Twenty patients had blood samples drawn immediately before and at hourly intervals after the start of CPB using either a conventional oxygenator and circuit (n = 14) or a covalently bonded heparin oxygenator and circuit (n = 6). Levels of IL-1, TNF-a, IL-6, and IL-8 were measured in all serum samples using a "sandwich" enzyme-linked immunosorbent assay. RESULTS: The levels of IL-6 and IL-8 increased in a time-dependent fashion in both groups, but the response was significantly less over time in the heparin-bonded group (p < 0.05) for both IL-6 and IL-8. Levels of IL-1 and TNF-a were not significantly elevated with lengthening bypass interval in either group. CONCLUSIONS: These data indicate that the use of heparin-coated bypass pump circuits results in lower serum levels of the inflammatory cytokines IL-6 and IL-8 than standard circuits. Biocompatible materials that decrease the inflammatory response to CPB may ultimately reduce the morbidity associated with cardiac operations.

Adult↗

PubMed2002

Physicochemical principles of tissue material interactions.

Biocompatibility of a material has to be adapted to the specific properties of the locus of application that are the type of tissue and the composition of extracellular fluid or the blood being in contact with the surface. The biocompatibility is beyond that greatly influenced by the design of the medical device which has to be planned close to the material's properties and the function within the body. Physical chemical reactions at and physical properties of the surface which influence the adsorption behavior for biomacromolecules. Conformational or functional changes of f.i. proteins due to physical forces originating from the surface could be the communication messages to the immunological system. The immersion of a material into an aqueous electrolyte leads generally to a space charge layer on both sides of the interface forming the electrical double layer, physically described by the isoelectric point of the materials surface. A numerical example hints on the importance of the double layer structure for the 'communication' between an implant and the surrounding extracellular fluid including beside ions complex structured proteins as biomacromolecules. Biocompatibility depends on the physical structure of the material and physicochemical properties of the interface to the biosystem. The conductivity of the surface film control reactions across the interface with biomacromolecules of the biological environment. Conformational unchanged macromolecules are the prior condition for biocompatibility and controls the attachment and probably also the degree of attachment via adhesion proteins. Later on, when the cells develop tension through the cytoskeleton on these attachment sites, the strength of the integrin adhesion protein-matrix protein interaction might probably prove decisive in differentiation state of the cell. It has been proved by molecular biological methods that an undestroyed oxide layer of anatase on titanium through passivation leaves for instance albumin conformational unchanged.

Adsorption↗

PubMed1990

Surface physics methods and in vitro bone-biomaterial interface control.

After a brief review of the main characteristics of some spectroscopic and microscopic methods for surface and interface analysis, preliminary and prospective studies of biocompatible materials (hydroxyapatite, alumina) for implant coating purposes are presented. The results show that the use of complementary techniques allows information on the physical and chemical properties of the coatings both on a microscopic and on an atomic scale to be obtained.

Aluminum Oxide↗

PubMed1987

A model for sidewall adhesions in the rabbit: reduction by an absorbable barrier.

Despite use of surgical adjuvants, pelvic adhesions frequently develop following infertility surgery. Recently a resorbable biocompatible material, TC 7, has been designed to be used as a barrier to reduce adhesion formation. Reproducibly severe sidewall adhesions were only able to be created in one of six models tested. The model consisted of the following steps: excision of a full thickness 2 x 2-cm musculoperitoneal tissue mass, scraping of an adjacent 2-cm length of uterine horn, tamponading of all bleeding, and suturing (6-0 Vicryl) of normal tube and sidewall so as to directly approximate the traumatized tissues. Studies were conducted in 13 rabbits after creation of the bilateral sidewall and horn lesions, each serving as its own control. Choice of control and TC 7 sides was determined randomly. Adhesion formation was examined 2 weeks postoperatively. No residual material was noted at that time. Adhesion scores were the composite total of extent (0-4), type (0-4), and tenacity (0-3) of sidewall adhesions, and were significantly reduced on the TC 7 side as compared with the control side (mean 6.8 +/- 0.4 vs 9.0 +/- 0.3, median 6 vs 9, sign test P = 0.0032). No complications of use of the barrier were noted. It is concluded that use of TC 7, a resorbable biocompatible barrier, was able to significantly reduce postoperative adhesion formation on the rabbit sidewall.

Animals↗

PubMed1999

Subcutaneous inflammatory reaction to a synthetic auditory ossicle (Bioceram) in rats.

Cellular response and inflammatory reaction to synthetic auditory ossicle (Bioceram) made from aluminium oxide are investigated. Local inflammatory effects are important in wound healing and in determining biocompatibility of an implant, necessitating the study of biologic effects of implants, especially inflammation and fibrous capsule formation. Bioceram discs were implanted subcutaneously in the interscapular region of rats for various periods of time, ranging from 1 day to 300 days. Histological sections 6 microns thick were stained with haematoxylin and eosin. Cell types around the implants were examined quantitatively by light microscopy. Inflammatory cell reaction to Bioceram decreased rapidly within 14 days, similar to the reaction in control groups. From 30 days to 300 days after implantation, there was continuous reduction to very low levels for macrophages and lymphocytes, but fibrous connective tissue capsule around implants matured. Preliminary results suggest that Bioceram is a satisfactory biocompatible material for reconstructive surgery from the viewpoint of cellular response. We also briefly discuss the different tissue responses in light of our previous study on hydroxyapatite (Apaceram).

Aluminum Oxide↗