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PubMed2006

An arteriovenous loop in a protected space generates a permanent, highly vascular, tissue-engineered construct.

A major obstacle to 3-dimensional tissue engineering is incorporation of a functional vascular supply to support the expanding new tissue. This is overcome in an in vivo intrinsic vascularization model where an arteriovenous loop (AVL) is placed in a noncollapsible space protected by a polycarbonate chamber. Vascular development and hypoxia were examined from 3 days to 112 days by vascular casting, morphometric, and morphological techniques to understand the model's vascular growth and remodeling parameters for tissue engineering purposes. At 3 days a fibrin exudate surrounded the AVL, providing a scaffold to migrating inflammatory, endothelial, and mesenchymal cells. Capillaries formed between 3 and 7 days. Hypoxia and cell proliferation were maximal at 7 days, followed by a peak in percent vascular volume at 10 days (23.20+/-3.14% compared with 3.59+/-2.68% at 3 days, P<0.001). Maximal apoptosis was observed at 112 days. The protected space and spontaneous microcirculatory development in this model suggest it would be applicable for in vivo tissue engineering. A temporal window in a period of intense angiogenesis at 7 to 10 days is optimal for exogenous cell seeding and survival in the chamber, potentially enabling specific tissue outcomes to be achieved.

Animals↗
PubMed2001

Tissue-engineered bone repair of sheep cranial defects with autologous bone marrow stromal cells.

Cranial bone defect remains a major challenge to craniofacial surgeons because of limited availability of autologous bone graft to repair the defects and the donor site defects secondary to tissue harvesting. In contrast, tissue-engineering technique can generate a large bone tissue using small amount of autologous cells and therefore avoid these problems. Bone Marrow Stromal Cells (MSCs) have the potential of multi-lineage (including osteogenic) differentiation. The objective of this study was to investigate the potential of using autologous MSCs to repair cranial bone defects by a tissue-engineering approach. Autologous MSCs were isolated from eight adult sheep respectively and were in vitro expanded and induced to become osteogenic cells. Bilateral full-thickness defects (20 mm in diameter) of parietal bones were created in animals and the bone defects were either repaired with the bone implants constituted with MSCs and calcium alginate at the experimental side (n = 8) or treated with calcium alginate only without MSCs (n = 4) or left unrepaired (n = 4) at the control side. New bone tissues were observed either grossly or histologically at the defects of experimental group as early as 6 weeks post-repairing, but not in control groups. The engineered bone tissue became more mature at 18 weeks post-repairing. Three-dimensional computerized tomography (CT) scan revealed an almost complete repair of the defect of experimental group at 18 weeks. This study may provide insight for future clinical repair of cranial defect.

Alginates↗
PubMed1999

Bioactive factors for bone tissue engineering.

Orthopaedic surgery is currently in the midst of a transformation from bone grafting and the use of bone graft substitutes to bone tissue engineering. Bioactive bone growth factors likely will play a particularly important role in this emerging field. This article will review the three leading strategies for using bioactive factors for bone tissue engineering: extraction and partial purification of growth factors, recombinant protein synthesis, and gene therapy. Preclinical and early clinical trial results with bone morphogenetic protein-2, bone morphogenetic protein-7 (osteogenic protein-1), and NeOsteo bovine bone protein extract will be reviewed. In addition, the current obstacles to clinical implementation of bone tissue engineering will be reviewed.

Animals↗
PubMed1999

Cartilage tissue engineering: current limitations and solutions.

Articular cartilage repair remains one of the most intensely studied orthopaedic topics. To date the field of tissue engineering has ushered in new methodologies for the treatment of cartilage defects. The authors' 10-year experience using principles of tissue engineering applied to resurfacing of cartilage defects is reported. Which cell type to use, chondrocytes versus chondroprogenitor cells, and their inherent advantages and disadvantages are discussed. Chondrocytes initially were used as the preferred cell type but were shown to have long term disadvantages in models used by the authors. Mesenchymal stem cells can be used effectively to overcome the limitations experienced with the use of differentiated chondrocytes. The use of mesenchymal stem cells as platforms for retroviral transduction of genes useful in cartilage repair introduces the concept of gene modified tissue engineering. The fundamental conditions for promoting and conducting a viable cartilage repair tissue, regardless of which cell type is used, also were studied. Placement of a synthetic porous biodegradable polymer scaffold was found to be a requirement for achieving an organized repair capable of functionally resurfacing a cartilage defect. A new modular device for intraarticular fixation of various graft composites has been developed. This new cartilage repair device is composed of bioabsorbable polymers and is capable of being delivered by the arthroscope.

Animals↗
PubMed2001

Cartilage regeneration using principles of tissue engineering.

It is well known that articular cartilage in adults has a limited ability for self-repair. Numerous methods have been devised to augment its natural healing response, but these methods generally lead to filling of the defect with fibrous tissue or fibrocartilage, which lacks the mechanical characteristics of articular cartilage and fails with time. Recently, tissue engineering has emerged as a new discipline that amalgamates aspects from biology, engineering, materials science, and surgery and that has as a goal the fabrication of functional new tissues to replace damaged tissues. The emergence of tissue engineering has facilitated the generation of new concepts and the revival of old ideas all of which has allowed a fresh approach to the repair or regeneration of tissues such as cartilage. The collaborations between scientists with different backgrounds and expertise has allowed the identification of some key principles that serve as the basis for the development of therapeutic approaches that now are less empiric and more hypothesis-driven than ever before. The current authors review some of the considerations regarding the various models used to test and validate the above repair methods and to address different aspects of the cartilage repair paradigm. Also, some key principles identified from past and current research, the need for the development of new biomaterials, and considerations in scale-up of cell-biomaterial constructs are summarized.

Age Factors↗
PubMed2001

Biodegradable polymer scaffolds for cartilage tissue engineering.

Cartilage defects are common, painful conditions and none of the currently available treatment options are satisfactory. Tissue engineering techniques involving scaffolds made from biodegradable synthetic polymers hold great promise for the future. These materials can be manufactured in an injectable form for minimally invasive procedures or in a preformed state to treat large irreparable lesions including arthritis. The mechanical and biologic properties of synthetic polymers can be tailored to different clinical applications and engineering strategies. The scaffold serves as a mechanical substrate for cells and bioactive factors and can help direct and organize the process of regeneration. The ultimate goal of tissue engineering is to recapitulate normal organogenesis to create histologically and functionally normal tissue. A review of the characteristics and potential of synthetic polymers shows that these substances will play a major role in treating cartilage disorders.

Absorbable Implants↗
PubMed2002

Tissue engineering skeletal muscle for orthopaedic applications.

With current technology, tissue-engineered skeletal muscle analogues (bioartificial muscles) generate too little active force to be clinically useful in orthopaedic applications. They have been engineered genetically with numerous transgenes (growth hormone, insulinlike growth factor-1, erythropoietin, vascular endothelial growth factor), and have been shown to deliver these therapeutic proteins either locally or systemically for months in vivo. Bone morphogenetic proteins belonging to the transforming growth factor-beta superfamily are osteoinductive molecules that drive the differentiation pathway of mesenchymal cells toward the chondroblastic or osteoblastic lineage, and stimulate bone formation in vivo. To determine whether skeletal muscle cells endogenously expressing bone morphogenetic proteins might serve as a vehicle for systemic bone morphogenetic protein delivery in vivo, proliferating skeletal myoblasts (C2C12) were transduced with a replication defective retrovirus containing the gene for recombinant human bone morphogenetic protein-6 (C2BMP-6). The C2BMP-6 cells constitutively expressed recombinant human bone morphogenetic protein-6 and synthesized bioactive recombinant human bone morphogenetic protein-6, based on increased alkaline phosphatase activity in coincubated mesenchymal cells. C2BMP-6 cells did not secrete soluble, bioactive recombinant human bone morphogenetic protein-6, but retained the bioactivity in the cell layer. Therefore, genetically-engineered skeletal muscle cells might serve as a platform for long-term delivery of osteoinductive bone morphogenetic proteins locally.

Alkaline Phosphatase↗
PubMed2004

Preincubation of tissue engineered constructs enhances donor cell retention.

Cartilage tissue engineering has been the focus of considerable research. However, the fate of transplanted donor cells rarely is explored directly. In the current study, the effect of preincubating perichondrial cells into a polylactic acid scaffold before implantation into an osteochondral defect was studied. The extracellular matrix produced during preincubation was characterized; the viability of the donor cells was assessed; and the retention of the donor cells in the repair tissue was determined using a gene marker on the Y chromosome, the gender-determining region Y gene. During in vitro incubation, the cells produced an extracellular matrix consisting of glycosaminoglycans, and Types I and II collagen, and the cell viability remained great. In vivo, preincubated constructs had significantly greater retention of donor cells in the host repair tissue in the short term when compared with nonincubated controls. This study shows the value of preincubating engineered constructs before implantation, and additionally validates the gender-determining region Y gene as an effective tool for assessing the fate of donor cells in cartilage tissue engineering.

Animals↗
PubMedDate not supplied

The professional development degree for biomedical engineers.

This paper examines the role of biomedical engineers in terms of their influence on the quality of health care delivery, and their need to continue their education in an effort to keep pace with technological advancements and prepare for career changes. This paper also examines the role of the Professional Development Degree for Engineers as one alternative to traditional degree programs, and describes one biomedical engineer's experience with a PDD program.

Biomedical Engineering↗
PubMedDate not supplied

Management concepts in clinical engineering.

The social and economic environment surrounding health care delivery is forcing improved financial management. The resulting responsibilities within health care institutions create the need for Clinical Engineers to develop improved management skills. Along with more traditional evaluation of technologies, these skills must be developed in the areas of Personnel and Data Management. The primary tool is a P.M./Repair Documentation System that can provide the data necessary for adequate manpower management, especially such factors as productivity and effectiveness. In addition, concepts previously foreign to engineers, such as group and human behavior, policy and program analysis, and organizational structure, must become part of the Clinical Engineers' working knowledge.

Maintenance and Engineering, Hospital↗
PubMedDate not supplied

Clinical engineering productivity improvement.

The recent focus on productivity in hospitals due to DRGs, shorter length of patient stays, and lower census has impacted clinical engineering departments. To have an effective and productive clinical engineering program, several organizational and personnel factors should be considered. By integrating these factors with other technical factors, productivity will eventually be improved. Productivity programs, such as Quality Circles, task changes, and shop automation, can have a significant impact on improving productivity. In addition, continued measurement of the effectiveness of the overall clinical engineering department is necessary to determine the effectiveness of productivity improvement programs.

Communication↗
PubMedDate not supplied

1990 survey of hospital salaries & job responsibilities for clinical engineers & biomedical technicians.

The Journal of Clinical Engineering has conducted its fifth survey of the salaries paid to Clinical Engineers and Biomedical Equipment Technicians in U.S. hospitals. This paper reports the salary and work responsibility data obtained from 1,453 professionals in relationship to: Certification; Region of the U.S.; Teaching Versus Nonteaching Facilities; Years of Experience; Education; Union Membership; and Gender. Data are included on Wage Increases and Job Responsibilities. All data are as of 12/31/89. The average BMET I has 3.3 years of experience and earns $19,394 +/- $4,144 (Std. Dev.). The average BMET II has 6.4 years of experience and earns $26,166 +/- $4,900. The average BMET III has 11.7 years of experience and earns $31,334 +/- $4,977. The average BMET Supervisor has 12.9 years of experience and earns $35,371 +/- $6,416. The average Clinical Engineer has 9.5 years of experience and earns $36,971 +/- $7,515. CE Supervisors are the highest paid in the field with an average 13.3 years of experience and an average salary of $46,265 +/- $11,115. Wages remain the highest on the West Coast and lowest in the Southeast. From 1988 to 1989, the wage ranges for all job types except BMET Is increased: BMET IIs, +1.9%; BMET IIIs, +3.0%; BMET Supervisors, +3.2%; CEs, +3.9%; and CE Supervisors, +1.8%. The highest quartile of CE Supervisors now earns between $52,000 and $95,000 per year. While certified individuals earn $521 to $4,953 more than noncertified, this is attributable in part to years of experience.

Age Factors↗
PubMedDate not supplied

Advancing biomedical engineering in developing nations: Project HOPE and the potential impact of nongovernmental organizations.

Nongovernmental organizations (NGOs) have played a major role in the diffusion of biomedical engineering training to developing nations. This paper reviews the roles and unique attributes of NGOs in biomedical engineering training programs. The activities of one leading NGO in this field, Project HOPE, are discussed with examples drawn from around the world. Future challenges to biomedical engineering in the developing world, and the potential of NGOs to provide a response to these needs, are considered.

Biomedical Engineering↗
PubMed2004

Engineered allergens for immunotherapy.

PURPOSE OF REVIEW: Specific immunotherapy is a clinically effective causative treatment for allergic conditions. However, the reagents used for immunotherapy are crude extracts prepared from natural sources with potential life-threatening anaphylactic side effects. Molecular cloning of allergens has made it feasible to design novel therapeutic approaches for improved and safer forms of allergen-specific immunotherapy. The purpose of this review is to examine recent advances made in the last 2 years in genetic engineering of allergens for specific immunotherapy. RECENT FINDINGS: Genetic engineering of allergen with nil or low IgE reactivity but retained T-cell reactivity offers a novel therapeutic approach to improving safety and efficacy of allergen-specific immunotherapy. Hypoallergenic forms of major allergens have been produced, with reduced IgE epitopes while preserving other characteristics of the molecule to induce a protective response. SUMMARY: Hypoallergenic forms of major allergens are potential candidates for allergen-specific immunotherapy in the future. These genetically engineered hypoallergens now need to be tested in clinical trials before being widely used. Safer and more efficacious vaccines would increase patient compliance leading to extensive use of immunotherapy.

Air Pollutants↗
PubMed2004

Tissue-engineered composites of anulus fibrosus and nucleus pulposus for intervertebral disc replacement.

STUDY DESIGN: By the technique of tissue engineering, composite intervertebral disc implants were fabricated as novel materials for disc replacement, implanted into athymic mice, and removed at times up to 12 weeks. OBJECTIVES: The goal of this study was to construct composite intervertebral disc structures consisting of anulus fibrosus cells and nucleus pulposus cells seeded on polyglycolic acid and calcium alginate matrices, respectively. SUMMARY OF BACKGROUND DATA: Previous work has documented the growth of anulus fibrosus cells on collagen matrices and nucleus pulposus cells cultured on multiple matrices, but there is no documentation of composite disc implants. METHODS: Lumbar intervertebral discs were harvested from sheep spine, and the nucleus pulposus was separated from surrounding anulus fibrosus. Each tissue was digested in collagenase type II. After 3 weeks in culture, cells were seeded into implants. The shape of the anulus fibrosus scaffold was fabricated from polyglycolic acid and polylactic acid, and anulus fibrosus cells were pipetted onto the scaffold and allowed to attach for 1 day. Nucleus pulposus cells were suspended in 2% alginate and injected into the center of the anulus fibrosus. The disc implants were placed in the subcutaneous space of the dorsum of athymic mice and harvested at 4, 8, and 12 weeks. At each time point, 4 samples were stored in -70 degrees C for collagen typing and analysis of proteoglycan, hydroxyproline, and DNA. Other samples were fixed in 10% formalin for Safranin-O staining. RESULTS: The gross morphology and histology of engineered discs strongly resembled those of native intervertebral discs. Biochemical markers of matrix synthesis were present, increasing with time, and were similar to native tissue at 12 weeks. Tissue-engineered anulus fibrosus was rich in type I collagen but nucleus pulposus contained type II collagen, similar to the native disc. CONCLUSION: These results demonstrate the feasibility of creating a composite intervertebral disc with both anulusfibrosus and nucleus pulposus for clinical applications.

Animals↗
PubMed2002

Engineering of human cartilage rods: potential application for penile prostheses.

PURPOSE: Natural penile prostheses created from the patient's own cells may eliminate the biocompatibility risks associated with artificial prostheses. We previously demonstrated that autologous cartilaginous rods could be created in animal corpus cavernosum as penile prostheses in situ by transplanting autologous chondrocytes on biodegradable polymer scaffolds. In the present study we investigated the possibility of engineering human cartilage rods for potential use as penile prostheses. MATERIALS AND METHODS: Chondrocytes isolated from human ear were seeded on rod shaped biodegradable polymer scaffolds (1.2 cm. in diameter, 6.0 cm. long). The seeded scaffolds were maintained in stirred bioreactors for 1 month. Subsequently, the seeded scaffolds were implanted subcutaneously into athymic rats. The specimens were retrieved 2 months after implantation, and histological, structural and mechanical properties were analyzed. The mechanical properties of the engineered prostheses were compared to those of silicone prostheses. RESULTS: Human chondrocytes seeded onto polymer scaffolds formed milk-white cartilaginous rods of the same size as the initial implants. Histological analyses using hematoxylin and eosin, toluidine blue and alcian blue showed mature and well-formed chrondrocytes in the retrieved implants. The engineered human cartilaginous rods were flexible, elastic and able to withstand high degrees of compressive forces. The mechanical properties were comparable to those of commercially available silicone prostheses. CONCLUSIONS: Transplantation of chrondrocytes isolated from human ear on polymer scaffolds resulted in the formation of human cartilage rods with the appropriate mechanical properties required for use as penile prostheses. This study demonstrates the feasibility of creating human cartilage rods with a large dimension. This technology may be useful for patients who need penile reconstruction.

Biomechanical Phenomena↗
PubMed2006

Recent developments in tissue engineering and regenerative medicine.

PURPOSE OF REVIEW: Currently, patients suffering from diseased and injured organs are treated with transplanted organs or cells. There is, however, a severe shortage of donor tissues and organs that is worsening yearly given the aging population. This paper reviews recent advances that have occurred in regenerative medicine and describes applications of new technologies to treat diseased or damaged organs and tissues. RECENT FINDINGS: Most current strategies for tissue engineering depend upon a sample of autologous cells from the diseased organ of the patient. Biopsies from patients with extensive end-stage organ failure, however, may not yield enough normal cells. In these situations, stem cells are envisioned as being an alternative source. Stem cells can be derived from discarded human embryos (human embryonic stem cells), from fetal tissue or from adult sources (bone marrow, fat, skin). Therapeutic cloning offers a potentially limitless source of cells for tissue engineering applications. SUMMARY: Increasingly, scientists in the fields of regenerative medicine and tissue engineering have applied 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.

Animals↗
PubMed2005

Producing a flexible tissue-engineered cartilage framework using expanded polytetrafluoroethylene membrane as a pseudoperichondrium.

BACKGROUND: Both native and engineered cartilage is brittle and fractures easily without perichondrium. The aim of this study was to understand the role of the perichondrium and try to enhance the flexible properties of tissue-engineered cartilage using expanded polytetrafluoroethylene (ePTFE) membrane as a pseudoperichondrium. METHODS: The study was conducted in two phases. In phase I, native swine auricular cartilage of different thicknesses was studied by histologic evaluation and failure testing. Next, isolated perichondrium was bonded to native cartilage slices using fibrin glue or Dermabond and tested to failure. In phase II, swine auricular chondrocytes were suspended in fibrin glue. The chondrocyte-fibrin glue composites were then bound to expanded polytetrafluoroethylene membrane in two trilaminar configurations: In group EC-1, the membrane was in the center, whereas it was on the surfaces in group EC-2. Specimens were implanted into nude mice for 4 weeks, 8 weeks, 12 weeks, and 8 months and subjected to histologic evaluation and failure testing. RESULTS: In phase I, the results demonstrated that perichondrium securely bonded to the cartilage plays an important role in maintaining the flexible nature of elastic cartilage. In phase II, failure testing revealed that specimens in group EC-1 (expanded polytetrafluoroethylene core) were fractured during bending and destroyed after torsion, whereas those in group EC-2 (cartilage core) returned to their original shape without fracturing even after rigorous torsion. Histologic analysis demonstrated that transplanted chondrocytes penetrated into the microporous structure of expanded polytetrafluoroethylene and created a bond to it. CONCLUSION: It is possible to engineer flexible cartilage using expanded polytetrafluoroethylene as a pseudoperichondrium.

Animals↗