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PubMedDate not supplied

Adipose tissue engineering: the future of breast and soft tissue reconstruction following tumor resection.

Reconstructive surgeons have always been at the forefront of medical technology. The history of reconstructive surgery began with ablative surgery, which was followed by tissue and organ transplantation, leading to contemporary tissue reconstruction. The field of reconstructive surgery is poised at the next stage of its evolution, namely tissue regeneration. The field of tissue engineering has largely defined this evolutionary leap. One active area of investigation is the development of tissue engineering strategies for adipose tissue. Bioengineers, life scientists, and reconstructive surgeons are synergistically coupling expertise in areas such as cell culture technology, tissue transfer, cell differentiation, angiogenesis, computer modeling, and polymer chemistry to regenerate adipose tissue de novo for breast replacement and soft-tissue augmentation following tumor resection. This work presents the current state of the art in adipose tissue engineering, as well the clinically translatable strategies currently under development. Semin. Surg. Oncol. 19:302-311, 2000.

Adipose Tissue↗
PubMed2000

Skin grafting for venous leg ulcers.

BACKGROUND: Venous leg ulceration is a common, recurring, disabling condition affecting up to 1% of adults. Treatment is aimed at healing with simple dressings and compression bandages / stockings. Unfortunately in some cases this treatment is unsuccessful with ulcers remaining open for months or years. In order to stimulate healing, some clinicians use skin grafts. These skin grafts may be taken from the patients own uninjured skin (e.g. thigh), may be grown from the patient's skin cells into a dressing, (both known as autografts) or applied as a sheet of bioengineered skin grown from a donor cells (known as an allograft). Preserved skin from other animals, e.g. pigs, have also been used and these are known as xerografts. OBJECTIVES: To assess the effectiveness of skin grafts in the treatment of venous leg ulcers. SEARCH STRATEGY: We searched the Cochrane Wounds Groups specialised register (date of search October 1999), and reference lists of relevant articles. We hand searched relevant journals and conference proceedings, and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials evaluating skin grafts in the treatment of venous leg ulcers. There was no restriction on articles based on language or publication status. DATA COLLECTION AND ANALYSIS: Data extraction and assessment of study quality was undertaken by two reviewers independently. Trials with similar patients, comparisons, and outcomes were pooled. MAIN RESULTS: Seven RCTs of skin grafts for venous leg ulcers were identified. In 6 trials patients also received compression bandaging. Two trials (98 patients) evaluated split thickness autografts, three trials (92 patients) evaluated cultured keratinocyte allografts, one compared tissue engineered skin (artificial skin) with a dressing (309 patients) and one compared it with a split thickness skin graft (7 patients, 13 ulcers). The trials comparing artificial skin with a dressing reported a significantly higher proportion of ulcers healing with artificial skin. There was insufficient evidence from the remaining trials to determine whether other types of skin grafting increased the healing of venous ulcers. REVIEWER'S CONCLUSIONS: There is limited evidence that artificial skin used in conjunction with compression bandaging, increases the chance of healing a venous ulcer compared to compression alone. Further research is needed to assess whether other forms of skin grafts increase ulcer healing.

Adult↗
PubMed2005

Skin grafting for venous leg ulcers.

BACKGROUND: Venous leg ulceration is a common and disabling condition which often recurs. It affects up to one in 100 adults at some time. The usual treatments are simple dressings and compression bandages or stockings. Unfortunately, in some cases this treatment is unsuccessful, with ulcers remaining open for months or years. Sometimes skin grafts are used to stimulate healing. These skin grafts may be taken from the patient's own uninjured skin, may be grown from the patient's skin cells into a dressing (autografts), or applied as a sheet of bioengineered skin grown from donor cells (allograft). Preserved skin from other animals, such as pigs, has also been used; these grafts are known as xerografts. OBJECTIVES: To assess the effect of skin grafts for treating venous leg ulcers. SEARCH STRATEGY: We searched the Cochrane Wounds Group Specialised Register (June 2004) and the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2004). SELECTION CRITERIA: Randomised controlled trials (RCTs) of skin grafts in the treatment of venous leg ulcers. DATA COLLECTION AND ANALYSIS: Two reviewers independently undertook data extraction and assessment of study quality. MAIN RESULTS: Nine trials of skin grafts for venous leg ulcers were identified, involving 579 participants. The trials were generally of poor methodological quality. In eight trials participants also received compression bandaging. Two trials (98 participants) evaluated split thickness autografts (one against a dressing and one against a xerograft), four trials (119 participants) evaluated cultured keratinocyte grafts (3 allografts and 1 autograft) , two compared tissue engineered skin (bilayer artificial skin) with a dressing (345 participants), and one compared it with a split thickness skin graft (7 participants, 13 ulcers). The trials comparing bilayer artificial skin with a dressing reported a significantly higher proportion of ulcers healing with artificial skin. There was not enough evidence from the other trials to determine whether other types of skin grafting increased the healing of venous ulcers. AUTHORS' CONCLUSIONS: There is evidence that a bilayer artificial skin, used in conjunction with compression bandaging, increases the chance of healing a venous ulcer compared with compression and a simple dressing. Further research is needed to assess whether other forms of skin grafts increase ulcer healing.

Adult↗
PubMed2002

Adaption of a fragment analysis technique to an automated high-throughput multicapillary electrophoresis device for the precise qualitative and quantitative characterization of microbial communities.

The analysis of microbial communities is of increasing importance in life sciences and bioengineering. Traditional techniques of investigations like culture or cloning methods suffer from many disadvantages. They are unable to give a complete qualitative and quantitative view of the total amount of microorganisms themselves, their interactions among each other and with their environment. Obviously, the determination of static or dynamic balances among microorganisms is of fast growing interest. The generation of species specific and fluorescently labeled 16S ribosomal DNA (rDNA) fragments by the terminal restriction fragment length polymorphism (T-RFLP) technique is a suitable tool to overcome the problems other methods have. For the separation of these fragments polyacrylamide gel sequencers are preferred as compared to capillary sequencers using linear polymers until now because of their higher electrophoretic resolution and therefore sizing accuracy. But modern capillary sequencers, especially multicapillary sequencers, offer an advanced grade of automation and an increased throughput necessary for the investigation of complex communities in long-time studies. Therefore, we adapted a T-RFLP technique to an automated high-throughput multicapillary electrophoresis device (ABI 3100 Genetic Analysis) with regard to a precise qualitative and quantitative characterization of microbial communities.

Bacteria↗
PubMed2006

Heuristic problems in defining the three-dimensional arrangement of the ventricular myocytes.

There is lack of consensus concerning the three-dimensional arrangement of the myocytes within the ventricular muscle masses. Bioengineers are seeking to model the structure of the heart. Although the success of such models depends on the accuracy of the anatomic evidence, most of them have been based on concepts that are far from anatomical reality, which ignore many significant previous accounts of anatomy presented over the past 400 years. During the 19th century, Pettigrew emphasized that the heart was built on the basis of a modified blood vessel rather than in the form of skeletal muscles. This fact was reemphasized by Lev and Simkins as well as Grant in the 20th century, but the caveats listed by these authors have been ignored by proponents of two current concepts, which state either that the myocardium is arranged in the form of a "unique myocardial band," or that the walls of the ventricles are sequestrated in uniform fashion by laminar sheets of fibrous tissue extending from epicardium to endocardium. These two concepts are themselves incompatible and are further at variance with the majority of anatomic studies, which have emphasized the regional heterogeneity to be found in the three-dimensional packing of the myocytes within a supporting matrix of fibrous tissue. We reemphasize the significance of this three-dimensional muscular mesh, showing how the presence of intruding aggregates of myocytes extending in oblique transmural fashion also contends against the notion that all myocytes are orientated with their long axes parallel to the epicardial and enodcardial surfaces.

Animals↗
PubMedDate not supplied

Experimental hemarthrosis in the knee of the mature canine.

The knee joints of 14 skeletally mature mongrel dogs were subjected to a continuous hemarthrosis. Minimal morphologic changes of the articular cartilage did not occur until after 16 weeks. As early as 4 weeks, biochemical analyses showed a significant decrease in glycosaminoglycans (GAG) that became progressively more severe with time, whereas total collagen was not significantly altered until after 12 and 16 weeks. Bioengineering measurements of the experimental cartilage surfaces showed that the tissue becomes more deformable as well as less resistive to shear than the control at 8 weeks. These differences increased as the duration of hemarthrosis increased.

Animals↗
PubMed2006

A perspective of synthetic biology: assembling building blocks for novel functions.

Synthetic biology is a recently emerging field that applies engineering formalisms to design and construct new biological parts, devices, and systems for novel functions or life forms that do not exist in nature. Synthetic biology relies on and shares tools from genetic engineering, bioengineering, systems biology and many other engineering disciplines. It is also different from these subjects, in both insights and approach. Applications of synthetic biology have great potential for novel contributions to established fields and for offering opportunities to answer fundamentally new biological questions. This article does not aim at a thorough survey of the literature and detailing progress in all different directions. Instead, it is intended to communicate a way of thinking for synthetic biology in which basic functional elements are defined and assembled into living systems or biomaterials with new properties and behaviors. Four major application areas with a common theme are discussed and a procedure (or "protocol") for a standard synthetic biology work is suggested.

Biomimetics↗
PubMed2005

Stem cell-based composite tissue constructs for regenerative medicine.

A major task of contemporary medicine and dentistry is restoration of human tissues and organs lost to diseases and trauma. A decade-long intense effort in tissue engineering has provided the proof of concept for cell-based replacement of a number of individual tissues such as the skin, cartilage, and bone. Recent work in stem cell-based in vivo restoration of multiple tissue phenotypes by composite tissue constructs such as osteochondral and fibro-osseous grafts has demonstrated probable clues for bioengineered replacement of complex anatomical structures consisting of multiple cell lineages such as the synovial joint condyle, tendon-bone complex, bone-ligament junction, and the periodontium. Of greater significance is a tangible contribution by current attempts to restore the structure and function of multitissue structures using cell-based composite tissue constructs to the understanding of ultimate biological restoration of complex organs such as the kidney or liver. The present review focuses on recent advances in stem cell-based composite tissue constructs and attempts to outline challenges for the manipulation of stem cells in tailored biomaterials in alignment with approaches potentially utilizable in regenerative medicine of human tissues and organs.

Animals↗
PubMed2006

Bioprocess monitoring and computer control: key roots of the current PAT initiative.

This review article has been written for the journal, Biotechnology and Bioengineering, to commemorate the 70th birthday of Daniel I.C. Wang, who served as doctoral thesis advisor to each of the co-authors, but a decade apart. Key roots of the current PAT initiative in bioprocess monitoring and control are described, focusing on the impact of Danny Wang's research as a professor at MIT. The history of computer control and monitoring in biochemical processing has been used to identify the areas that have already benefited and those that are most likely to benefit in the future from PAT applications. Past applications have included the use of indirect estimation methods for cell density, expansion of on-line/at-line and on-line/in situ measurement techniques, and development of models and expert systems for control and optimization. Future applications are likely to encompass additional novel measurement technologies, measurements for multi-scale and disposable bioreactors, real time batch release, and more efficient data utilization to achieve process validation and continuous improvement goals. Dan Wang's substantial contributions in this arena have been one key factor in steering the PAT initiative towards realistic and attainable industrial applications.

Bioreactors↗
PubMed2007

Scale-up criteria of square tank surface aerator.

Oxygen transfer rate and the corresponding power requirement to operate the rotor are vital for design and scale-up of surface aerators. Present study develops simulation or scale-up criterion correlating the oxygen transfer coefficient and power number along with a parameter governing theoretical power per unit volume (X, which is defined as equal to F(4/3)R(1/3), where F and R are impellers' Froude and Reynolds number, respectively). Based on such scale-up criteria, design considerations are developed to save energy requirements while designing square tank surface aerators. It has been demonstrated that energy can be saved substantially if the aeration tanks are run at relatively higher input powers. It is also demonstrated that smaller sized tanks are more energy conservative and economical when compared to big sized tanks, while aerating the same volume of water, and at the same time by maintaining a constant input power in all the tanks irrespective of their size. An example illustrating how energy can be reduced while designing different sized aerators is given. The results presented have a wide application in biotechnology and bioengineering areas with a particular emphasis on the design of appropriate surface aeration systems.

Bioreactors↗
PubMed2006

Covalent microcontact printing of proteins for cell patterning.

We describe a straightforward approach to the covalent immobilization of cytophilic proteins by microcontact printing, which can be used to pattern cells on substrates. Cytophilic proteins are printed in micropatterns on reactive self-assembled monolayers by using imine chemistry. An aldehyde-terminated monolayer on glass or on gold was obtained by the reaction between an amino-terminated monolayer and terephthaldialdehyde. The aldehyde monolayer was employed as a substrate for the direct microcontact printing of bioengineered, collagen-like proteins by using an oxidized poly(dimethylsiloxane) (PDMS) stamp. After immobilization of the proteins into adhesive "islands", the remaining areas were blocked with amino-poly(ethylene glycol), which forms a layer that is resistant to cell adhesion. Human malignant carcinoma (HeLa) cells were seeded and incubated onto the patterned substrate. It was found that these cells adhere to and spread selectively on the protein islands, and avoid the poly(ethylene glycol) (PEG) zones. These findings illustrate the importance of microcontact printing as a method for positioning proteins at surfaces and demonstrate the scope of controlled surface chemistry to direct cell adhesion.

Aldehydes↗
PubMed2005

Regenerative and predictive medicine of cardiovascular disease: the 9th Leipziger Workshop and the 2nd International Workshop on slide based cytometry.

Slide-based cytometry (SBC) and related techniques offer unique tools to perform complex immunophenotyping, thereby enabling diagnostic procedures at very early disease stages. Multicolor or polychromatic analysis of cells by SBC is of special importance, not only as a cytomics technology platform but also for patients with low blood volume such as neonates. The exact knowledge of the location of each cell on the slide allows restaining and subsequent reanalysis of the specimen. These separate measurements of the same specimen can be fused to one data file (merging), thus increasing the information obtained per cell. Relocalization and optical evaluation of the cells, a feature typical of SBC, can be of integral importance for cytometric analysis. Due to this feature, artifacts can be excluded and morphology of measured cells can be documented. Predictive medicine aims at the detection of changes in patient's state before the manifestation of the disease or its complications. Such instances concern multiorgan failure in sepsis or noninfectious posttraumatic shock in intensive care patients or the pretherapeutic identification of high-risk patients undergoing cancer cytostatic therapy. Early anti-infectious or antishock therapy and curative chemotherapy in combination with stem cell transplantation may provide better chances of patients' survival at concomitant cost containment. Predictive medicine that guides early individualized decrease or cessation of therapy may lower or abrogate potential therapeutic side effects (individualized medicine). Regenerative medicine concerns patients who have diseased and injured organs and may be treated with transplanted organs. However, there is a severe shortage of donor organs that is worsening yearly given the aging population. Regenerative medicine and tissue engineering apply the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Neovascularization is promoted by bone marrow-derived endothelial progenitor cells that lead to the formation of entirely new vessels into ischemic tissue. With this knowledge, many therapeutical borders can be skipped. Diseases formerly uncontrolled can be corrected with stem cells to provide causal healing with regeneration processes. The 9th Leipziger Workshop combined with the 2nd International Workshop on SBC aimed to offer new methods in image cytometry and SBC for solutions in clinical research. It moved toward practical applications in clinics and the clinical laboratory. This development will be continued in 2005 at the upcoming Leipziger Workshop and the 3rd International Workshop on SBC.

Cardiovascular Diseases↗
PubMed1991

Drug delivery systems 5A. Oral drug delivery.

The two main advantages of controlled drug delivery systems are: maintenance of therapeutically optimum drug concentrations in the plasma through zero-order release without significant fluctuations; and elimination of the need for frequent single dose administrations. The oral and other therapeutic systems in human use have validated the concept that controlled continuous drug release can minimize the daily dose of a drug required to maintain the required therapeutic effect, while minimizing unwanted pharmacological effects. By minimizing patient intervention, a design feature of therapeutic systems, compliance is automatically enhanced. Oral drug delivery systems, in particular, have required innovation in materials science to provide materials biocompatible during prolonged contact with body tissues, bioengineering to develop drug delivery modules, and clinical pharmacology for elucidation of drug action under conditions of continuous controlled drug administration. Recent work in advanced oral delivery has been primarily focused on liposome technology and the concept that substances that are normally destroyed by the stomach can be protected long enough before they could be absorbed downstream. For cost and patient convenience, oral delivery certainly would be an attractive method. The nature of biologic substances, however, with their unique technical problems, will probably limit greatly those that can be delivered orally. Besides, where delivery rate control is critical, oral delivery, even when possible, would probably be insufficiently precise. Oral delivery would also limit the substance to bloodstream delivery to the disease site. Even so, oral controlled drug delivery systems will likely find primary usefulness in specific carefully controlled therapies and prophylactic situations with due regard for drug interactions. This system represents a potentially very significant therapeutic modality. These delivery systems will find usefulness primarily in certain well-defined and well-controllable areas with due regard for individual patient variations. The purpose of the present article is to review oral controlled-release drug delivery systems, with particular emphasis on the practical aspects of testing and fabricating these systems and the underlying mechanisms by which control over drug release rate is accomplished.

Administration, Oral↗
PubMed1995

Effectiveness of cleaning surgical implants: quantitative analysis of contaminant removal.

Surgical implants need to be free from contaminants before implantation. The effectiveness of a presently used Clemson bioengineering cleaning (CBC) protocol was evaluated for cleaning three different biomaterials (titanium, aluminum oxide, and polyethylene terephthalate, PET) contaminated with three different contaminants (calcium chloride, zinc chloride, and hexadecane). Radiolabeled tracer analysis (RTA), with the use of liquid scintillation, was used as the surface analytical technique to quantitatively determine the percent contaminant removed from the biomaterial surface. On average, the ultrasonic cleaning step removed 99.96% of all three contaminants from both titanium and aluminum oxide. The CBC protocol did not sufficiently clean PET fabric contaminated with hexadecane leaving 11.76% of the contaminant after the ultrasonic step. With the use of isopropyl alcohol in series with 1% Liquinox, the ultrasonic step cleaned the fabric soiled with hexadecane within 30 min, removing 99.85% of the hexadecane initially on the surface. RTA proved to be an excellent method of quantifying surface contamination on implant materials, and for assessing the effectiveness of cleaning protocols in question.

Alkanes↗
PubMed2002

Smooth muscle cell adhesion on crosslinked hyaluronan gels.

Hyaluronic acid (HA)-based polymers (hylans) are highly biocompatible and can be structurally modified to obtain desired mechanical properties. This study evaluated divinyl sulfone-crosslinked solid and particulate hylans as cellular scaffolds. These two hylan types differ in surface characteristics, mode of preparation, HA content, and extent of crosslinking. Neonatal rat aortic smooth muscle cells were cultured on hylan gels coated with matrix factors including collagen I, ECM gel, laminin, and fibronectin and on uncoated controls for < or =4 weeks. Cell attachment was sparse on uncoated controls but significantly enhanced on coated gels. Cell morphology was influenced by the identity of the matrix factors coated and the surface topography of the hylan gels. Cells attached to coated particulate gels appeared either highly spread (collagen, fibronectin) or irregularly shaped (ECM gel, laminin). Cells on laminin and fibronectin-coated solid gels were rounded and nonproliferative. Cells proliferated most rapidly on ECM gel-coated gels. The uneven surface of particulate gels induced more protein deposition and the subsequent attachment and active proliferation of cells. This study shows that surface texturizing and subsequent surface treatment with matrix factors enhances cell attachment and proliferation of hylans. These results are useful toward developing bioengineered materials based on cell-hylan composites.

Animals↗
PubMed1989

Creep studies of multiphase acrylic systems.

The influence of type and quantity of five different crosslinking agents on tensile creep properties of multiphase acrylic systems has been studied. The polymeric materials, commonly applied in bioengineering, were processed by polymerization of a mixture of liquid methacrylate monomers and poly(methyl methacrylate) powder. The specimens were made with various ratios of methyl methacrylate and crosslinking agents in the monomer liquid. Two different processing conditions were used, i.e., heat-polymerization at 100 degrees C and autopolymerization at 45 degrees C. Creep behavior was determined at 37 +/- 0.2 degrees C and 50 +/- 0.5 degrees C. The investigation showed higher creep values for autopolymerized than for heat-polymerized materials. In heat-polymerized materials the creep curves showed little variation with type and quantity of crosslinking agents at low stress levels. However, at high stress levels the creep values decreased with increasing quantity of crosslinking agents. The autopolymerized materials showed a more inhomogeneous structure, and great variation in creep. Both among the heat-polymerized and autopolymerized materials, the systems with diethyleneglycol dimethacrylate clearly deviated from the others by showing higher creep values.

Biopolymers↗
PubMed1990

Dynamic mechanical properties of multiphase acrylic systems.

The influence of type and quantity of five different dimethacrylate crosslinking agents on the dynamic mechanical properties of multiphase acrylic systems has been studied. These materials, commonly used in bioengineering, were processed by polymerization of a mixture of liquid methacrylate monomers, and poly(methyl methacrylate) powder. The specimens were made with various ratios of methyl methacrylate and dimethacrylate crosslinking agents in the monomer liquid. Two different processing conditions were used, heat-polymerization at 100 degrees C and autopolymerization at 45 degrees C. By using a forced torsional vibration apparatus the storage modulus (G'), loss modulus (G"), and dissipation factor (tan delta) were determined over the temperature range -60 degrees C to 140 degrees C at frequencies of 0.1, 1.0, 10, and 100 rad/s. In the autopolymerized materials, the glass transition temperature (Tg), as determined via tan delta data, increased with increasing quantities of crosslinking agents. The storage modulus likewise increased. In the heat-polymerized materials only minor variations in modulus and tan delta with type and quantity of crosslinking agents were observed. Tg values of the heat-polymerized materials were, in all cases, greater than those of the autopolymerized materials.

Biocompatible Materials↗
PubMed2004

Ultrastructure and nanomechanical properties of cementum dentin junction.

The attachment between cementum and dentin has been given several definitions and nomenclature, including: interzonal layer, intermediate cementum, collagen hiatus, Hopewell-Smith's hyaline layer, and more commonly, cementum-dentin junction (CDJ). Understanding the attachment of two structurally dissimilar hard tissues such as cementum and dentin defined by a junction may provide information necessary to engineer functionally graded materials that can be used for efficient tooth restorations in clinical dentistry and other bioengineering applications. Hence, in this study, as a first step toward understanding the CDJ using a biomechanical approach, it was hypothesized that the CDJ between cementum and dentin is a wide zone with mechanical properties significantly lower than the neighboring tissues. The structure of the CDJ was studied using an atomic force microscope (AFM), and site-specific mechanical response of the three regions; cementum, CDJ, and dentin were determined using an AFM-nanoindenter under dry and wet conditions. The AFM results of the CDJ demonstrated a valley under dry conditions and a peak under wet conditions. The magnitude of the depth of the valley was approximately the same as the height of the peak of the CDJ, ranging from 10 to 40 microm. The nanomechanical properties under dry conditions indicated no significant difference (p > 0.05) in elastic modulus and hardness of the CDJ (Er = 17.5 +/- 2.7 GPa, H = 0.6 +/- 0.1 GPa) and cementum (Er = 18.7 +/- 2.5 GPa, H = 0.6 +/- 0.1 GPa). The mechanical properties of the CDJ were significantly lower (p << 0.05) than dentin (Er = 19.9 +/- 2.9 GPa, H = 0.6 +/- 0.1 GPa) under dry conditions. However, under more relevant hydrated conditions, the mechanical properties of CDJ (Er 3.0 +/- 0.7 GPa, H = 0.1 +/- 0.0 GPa) were significantly lower (p << 0.05) than those of cementum (Er 6.8 +/- 1.9 GPa, H = 0.2 +/- 0.1 GPa) and dentin (Er 9.4 +/- 2.3 GPa, H = 0.3 +/- 0.1 GPa). Based on the results from this study, it can be concluded that the CDJ can be regarded as a wide zone containing large quantities of proteins including collagen that contribute to hydration and significantly reduce mechanical properties, compared with the adjacent hard tissues, cementum, and dentin. The lower mechanical properties of the CDJ may make it possible for it to redistribute occlusal loads to the alveolar bone.

Aged↗