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Biomedical subjects

D W Hutmacher

Publications and source records attributed to D W Hutmacher.

9 recordsLinked to original sources

[Individually CAD-CAM technique designed, bioresorbable 3-dimensional polycaprolactone framework for experimental reconstruction of craniofacial defects in the pig].

METHODS: Twenty orbital defects (2 x 2 cm) were created in ten adult Yorkshire pigs. Two software products (Velocity and Mimix) were evaluated with regard to image processing, three-dimensional reconstruction, and fabrication of individually shaped polycaprolactone (PCL) scaffolds to reconstruct these defects. Four different techniques were tested for the reconstruction: group 1 = no reconstruction, group 2 = polylactide sheet, group 3 = PCL scaffold, group 4 = bone marrow-coated PCL scaffold. The pigs were sacrificed at 3 months. RESULTS: In group 1 soft tissue scar formation could be found, but without any new bone. Group 2 showed a thick fibrous capsule around the PLLA sheet, whereas at the border zone of the defect signs of new bone formation could be detected. In group 3 the PCL scaffolds were filled with fibrous tissue and some areas that showed new bone formation (6.4% of the area of the defect). In group 4 the new bone formation (17.8% of the area of the defect) was significantly higher in quantity than in group 3. CONCLUSION: The PCL scaffold coated with bone marrow seems to be a material that effectively provides osteoinduction with formation of new bone. Long-term results at 12 months are still pending.

Absorbable Implants↗

In vivo mesenchymal cell recruitment by a scaffold loaded with transforming growth factor beta1 and the potential for in situ chondrogenesis.

The objectives of this study were (1) to develop a biphasic implant made of a bioresorbable polymeric scaffold in combination with TGF-beta1-loaded fibrin glue for tissue-engineering applications, and (2) to determine whether the implant made of a polycaprolactone (PCL) scaffold and TGF-beta1-loaded fibrin glue could recruit mesenchymal cells and induce the process of cartilage formation when implanted in ectopic sites. Twenty-four 6-month-old New Zealand White rabbits were used. Scaffolds loaded with various doses of TGF-beta1 in fibrin glue were implanted subcutaneously, intramuscularly, and subperiosteally. The rabbits were killed and implants were removed at 2, 4, and 6 weeks postoperatively. The specimens were subjected to various staining techniques for histological analysis. Light microscopic examination of all specimens revealed that the entire pore space of the scaffolds was filled with various tissues in each group. The entire volume of the scaffolds in the groups loaded with TGF-beta1 and implanted intramuscularly and subcutaneously was populated with mesenchymal cells surrounded with an abundant extracellular matrix and blood vessels. The scaffold loaded with TGF-beta1 and implanted subperiosteally was found to be richly populated with chondrocytes at 2 and 4 weeks and immature bone formation was identified at 6 weeks. We conclude that scaffolds loaded with TGF-beta1 can successfully recruit mesenchymal cells and that chondrogenesis occurred when this construct was implanted subperiosteally.

Animals↗

Mechanical properties and cell cultural response of polycaprolactone scaffolds designed and fabricated via fused deposition modeling.

A number of different processing techniques have been developed to design and fabricate three-dimensional (3D) scaffolds for tissue-engineering applications. The imperfection of the current techniques has encouraged the use of a rapid prototyping technology known as fused deposition modeling (FDM). Our results show that FDM allows the design and fabrication of highly reproducible bioresorbable 3D scaffolds with a fully interconnected pore network. The mechanical properties and in vitro biocompatibility of polycaprolactone scaffolds with a porosity of 61 +/- 1% and two matrix architectures were studied. The honeycomb-like pores had a size falling within the range of 360 x 430 x 620 microm. The scaffolds with a 0/60/120 degrees lay-down pattern had a compressive stiffness and a 1% offset yield strength in air of 41.9 +/- 3.5 and 3.1 +/- 0.1 MPa, respectively, and a compressive stiffness and a 1% offset yield strength in simulated physiological conditions (a saline solution at 37 degrees C) of 29.4 +/- 4.0 and 2.3 +/- 0.2 MPa, respectively. In comparison, the scaffolds with a 0/72/144/36/108 degrees lay-down pattern had a compressive stiffness and a 1% offset yield strength in air of 20.2 +/- 1.7 and 2.4 +/- 0.1 MPa, respectively, and a compressive stiffness and a 1% offset yield strength in simulated physiological conditions (a saline solution at 37 degrees C) of 21.5 +/- 2.9 and 2.0 +/- 0.2 MPa, respectively. Statistical analysis confirmed that the five-angle scaffolds had significantly lower stiffness and 1% offset yield strengths under compression loading than those with a three-angle pattern under both testing conditions (p < or = 0.05). The obtained stress-strain curves for both scaffold architectures demonstrate the typical behavior of a honeycomb structure undergoing deformation. In vitro studies were conducted with primary human fibroblasts and periosteal cells. Light, environmental scanning electron, and confocal laser microscopy as well as immunohistochemistry showed cell proliferation and extracellular matrix production on the polycaprolactone surface in the 1st culturing week. Over a period of 3-4 weeks in a culture, the fully interconnected scaffold architecture was completely 3D-filled by cellular tissue. Our cell culture study shows that fibroblasts and osteoblast-like cells can proliferate, differentiate, and produce a cellular tissue in an entirely interconnected 3D polycaprolactone matrix.

Biocompatible Materials↗

Evaluation of ultra-thin poly(epsilon-caprolactone) films for tissue-engineered skin.

Various natural and synthetic polymeric materials have been used as scaffold matrices for tissue-engineered skin. However, the commercially available skin replacement products pose problems of poor mechanical properties and immunological rejection. We have thus developed a film of 5 microm thickness, via biaxial stretching of poly(epsilon-caprolactone) (PCL), as a potential matrix for living skin replacements. The aim of this study was to evaluate the feasibility of using biaxially stretched PCL films as matrices for culturing human dermal fibroblasts. For this purpose, we cultured human dermal fibroblasts for 7 days on the films. Glass cover slips and polyurethane (PU) sheets were used as controls. The data from phase contrast light, confocal laser, and scanning electron microscopy suggested that biaxially stretched PCL films support the attachment and proliferation of human dermal fibroblasts. Thymidine-labeling results showed quantitatively that cell proliferation on the PCL films was superior to that on the PU samples. These results indicated that biaxially stretched PCL films supported the growth of human dermal fibroblasts and might have potential to be applied in tissue engineering a dermal equivalent or skin graft.

Bioprosthesis↗

Scaffold design and fabrication technologies for engineering tissues--state of the art and future perspectives.

Today, tissue engineers are attempting to engineer virtually every human tissue. Potential tissue-engineered products include cartilage, bone, heart valves, nerves, muscle, bladder, liver, etc. Tissue engineering techniques generally require the use of a porous scaffold, which serves as a three-dimensional template for initial cell attachment and subsequent tissue formation both in vitro and in vivo. The scaffold provides the necessary support for cells to attach, proliferate, and maintain their differentiated function. Its architecture defines the ultimate shape of the new grown soft or hard tissue. In the early days of tissue engineering, clinically established materials such as collagen and polyglycolide were primarily considered as the material of choice for scaffolds. The challenge for more advanced scaffold systems is to arrange cells/tissue in an appropriate 3D configuration and present molecular signals in an appropriate spatial and temporal fashion so that the individual cells will grow and form the desired tissue structures--and do so in a way that can be carried out reproducibly, economically, and on a large scale. This paper is not intended to provide a general review of tissue engineering, but specifically concentrate on the design and processing of synthetic polymeric scaffolds. The material properties and design requirements are discussed. An overview of the various fabrication techniques of scaffolds is presented, beginning with the basic and conventional techniques to the more recent, novel methods that combine both scaffold design and fabrication capabilities.

Animals↗

An introduction to biodegradable materials for tissue engineering applications.

Tissue generation by autogenous cell transplantation is one of the most promising treatment concepts being developed as it eliminates problems of donor site scarcity, immune rejection and pathogen transfer. Cultured cells are seeded onto a three-dimensional biocompatible scaffold that will slowly degrade and resorb as the soft and hard structures grow and assimilate in vitro and/or in vivo. The 3-D scaffold provides the necessary template for cells to proliferate and maintain their differentiated state. Ultimately, it defines the overall shape of the tissue-engineered transplant. The aim of this review is to describe and discuss the scaffold materials of natural and synthetic origin that are of specific interest to tissue engineers. This review is based on previous publications and our own experience in the use of biomaterials of natural and synthetic origin for tissue engineering applications. Biodegradable polymers which have been used for tissue engineering applications are mainly based on clinically established medical devices and implants. In the group of macromolecules of natural origin collagen, alginate, agarose, hyaluronic acid derivatives, chitosan, and fibrin glue have been used as scaffolds. Man-made polymers such as polyglycolide (PGA), polylactides (PLLA, PDLA), poly(caprolactone) (PCL), and poly(dioxanone) (PDS) have been studied as matrix material to guide the differentiation and proliferation of cells into the targeted functional premature and/or mature tissue. Appropriate selection of scaffold material with respect to the targeted tissue is essential. Today, biomaterials of choice remain to be those approved by the US Food and Drug Administration. In spite of that, novel biomaterials should be developed specifically designed for tissue engineering applications.

Absorbable Implants↗

A tissue engineered cell-occlusive device for hard tissue regeneration--a preliminary report.

Tissue engineering is an emerging discipline that applies engineering principles to create devices for the study, restoration, modification, and assembly of functional tissues and organs from native or synthetic sources. In the field of guided bone regeneration (GBR), cellular matter engineering has been applied, more or less successfully, to the development of biodegradable and bioresorbable devices with chemical, physical, or mechanical properties, structure, or form that permit active tissue integration with desirable cell types and tissue components. The employment of synthetic and naturally occurring polymers as well as sophisticated manufacturing technologies allow the tissue engineering of matrix configurations so that the biophysical limitations of mass transfer can be satisfied. The configuration of such a hybrid matrix can also be manipulated to vary the surface area available for cell attachment, as well as to optimize the exposure of the attached cells to nutrients. A biodegradable and bioresorbable device made of synthetic and natural polymers was engineered specifically for GBR procedures. The degradation and resorption kinetics as well as the mechanical properties give the device the potential to function as a carrier for bone growth factors. This innovative device was applied as a GBR membrane in a clinical investigation in seven patients.

Absorbable Implants↗

Scaffolds in tissue engineering bone and cartilage.

Musculoskeletal tissue, bone and cartilage are under extensive investigation in tissue engineering research. A number of biodegradable and bioresorbable materials, as well as scaffold designs, have been experimentally and/or clinically studied. Ideally, a scaffold should have the following characteristics: (i) three-dimensional and highly porous with an interconnected pore network for cell growth and flow transport of nutrients and metabolic waste; (ii) biocompatible and bioresorbable with a controllable degradation and resorption rate to match cell/tissue growth in vitro and/or in vivo; (iii) suitable surface chemistry for cell attachment, proliferation, and differentiation and (iv) mechanical properties to match those of the tissues at the site of implantation. This paper reviews research on the tissue engineering of bone and cartilage from the polymeric scaffold point of view.

Biocompatible Materials↗

Tissue engineering research: the engineer's role.

Tissue engineering holds the promise of revolutionary advances for health care. Academic, clinical and industrial efforts are increasingly directed towards the development of autogenic substitutes to restore, maintain, or improve tissue and organ functions. This article summarizes the role of the engineer in the multidisciplinary environment of tissue engineering research.

Bioreactors↗