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Biomedical subjects

S E Feinberg

Publications and source records attributed to S E Feinberg.

At least 19 recordsLinked to original sources

Engineering craniofacial scaffolds.

OBJECTIVE: To develop an integrated approach for engineering craniofacial scaffolds and to demonstrate that these engineered scaffolds would have mechanical properties in the range of craniofacial tissue and support bone regeneration for craniofacial reconstruction. EXPERIMENTAL VARIABLE: Scaffold architecture designed to achieve desired elasticity and permeability. Scaffold external shape designed to match craniofacial anatomy. OUTCOME MEASURE: Final fabricated biomaterial scaffolds. Compressive mechanical modulus and strength. Bone regeneration as measured by micro-CT scanning, mechanical testing and histology. SETTING: Departments of Biomedical Engineering, Oral/Maxillofacial Surgery, and Oral Medicine, Pathology and Oncology at the University of Michigan. RESULTS: Results showed that the design/fabrication approach could create scaffolds with designed porous architecture to match craniofacial anatomy. These scaffolds could be fabricated from a wide range of biomaterials, including titanium, degradable polymers, and degradable calcium phosphate ceramics. Mechanical tests showed that fabricated scaffolds had compressive modulus ranging 50 to 2900 MPa and compressive strength ranging from 2 to over 56 MPa, within the range of human craniofacial trabecular bone. In vivo testing of designed scaffolds showed that they could support bone regeneration via delivery of BMP-7 transduced human gingival fibroblasts in a mouse model. Designed hydroxyapatite scaffolds with pore diameters ranging from 400 to 1200 microns were implanted in minipig mandibular defects for 6 and 18 weeks. Results showed substantial bone ingrowth (between 40 and 50% at 6 weeks, between 70 and 80% at 18 weeks) for all scaffolds, with no significant difference based on pore diameter. CONCLUSION: Integrated image-based design and solid free-form fabrication can create scaffolds that attain desired elasticity and permeability while fitting any 3D craniofacial defect. The scaffolds could be manufactured from degradable polymers, calcium phosphate ceramics and titanium. The designed scaffolds supported significant bone regeneration for all pore sizes ranging from 300 to 1200 microns. These results suggest that designed scaffolds are clinically applicable for complex craniofacial reconstruction.

Animals↗

Intraoral grafting of an ex vivo produced oral mucosa equivalent: a preliminary report.

The objective of this study was to assess the efficacy of the use of an ex vivo produced oral mucosa equivalent (EVPOME) for intraoral grafting procedures. Autogenous keratinocytes were harvested from a punch biopsy 4 weeks prior to surgery, placed in a serum-free culture system and seeded onto a human cadaveric dermal equivalent, AlloDerm. Thirty patients with either a premalignant or cancerous lesion were triaged into two groups, depending on the stage of disease: Group 1: EVPOME or Group 2: AlloDerm, control without an epithelial layer. Clinically, EVPOME grafts were easy to handle and showed excellent compliance on grafting. Both, EVPOME and AlloDerm grafts, showed a 100% take rate. At 6 days post-grafting, the EVPOME clinically showed changes indicating vascular ingrowth and had cytologic evidence of the persistence of grafted cultured keratinocytes on the surface. The EVPOME grafts had enhanced maturation of the underlying submucosal layer associated with rapid epithelial coverage when compared to the AlloDerm grafts at biopsies taken at 28 days post-grafting. In summary, EVPOME appears to be an acceptable oral mucosal substitute for human intraoral grafting procedures and results in a more favorable wound healing response than AlloDerm alone.

Adult↗

Manufacturing and characterization of 3-d hydroxyapatite bone tissue engineering scaffolds.

Internal architecture has a direct impact on the mechanical and biological behaviors of porous hydroxyapatite (HA) implants. However, traditional processing methods provide very minimal control in this regard. This paper reviews a novel processing technique developed in our laboratory for fabricating scaffolds with controlled internal architectures. The preliminary mechanical property and in vivo evaluation of these scaffolds are also presented.

Animals↗

Hydroxyapatite implants with designed internal architecture.

Porous hydroxyapatite (HA) has been used as a bone graft material in the clinics for decades. Traditionally, the pores in these HAs are either obtained from the coralline exoskeletal patterns or from the embedded organic particles in the starting HA powder. Both processes offer very limited control on the pore structure. A new method for manufacturing porous HA with designed pore channels has been developed. This method is essentially a lost-mold technique with negative molds made with Stereolithography and a highly loaded curable HA suspension as the ceramic carrier. Implants with designed channels and connection patterns were first generated from a Computer-Aided-Design (CAD) software and Computer Tomography (CT) data. The negative images of the designs were used to build the molds on a stereolithography apparatus with epoxy resins. A 40 vol% HA suspension in propoxylated neopentyl glycol diacrylate (PNPGDA) and iso-bornyl acrylate (IBA) was formulated. HA suspension was cast into the epoxy molds and cured into solid at 85 degrees C. The molds and acrylate binders were removed by pyrolysis, followed by HA green body sintering. With this method, implants with six different channel designs were built successfully and the designed channels were reproduced in the sintered HA implants. The channels created in the sintered HA implants were between 366 microm and 968 microm in diameter with standard deviations of 50 microm or less. The porosity created by the channels were between 26% and 52%. The results show that HA implants with designed connection pattern and well controlled channel size can be built with the technique developed in this study.

Journal Article↗

Image-based biomimetic approach to reconstruction of the temporomandibular joint.

This article will present an image-based approach to the designing and manufacturing of biomimetic tissue engineered temporomandibular (TMJ) condylar prosthesis. Our vision of a tissue-engineered TMJ prosthesis utilizes a 3-D designed and manufactured biodegradable scaffold shaped similar to a condylar head and neck, i.e. a condylar-ramus unit (CRU). The fabricated CRU scaffold can be constructed with a specific intra-architectural design such that it will enhance the formation of tissue from implanted cells placed within its interstices. These biologic cues could influence scaffold-implanted mesenchymal stem cells (MSC) or bone marrow stromal cells (BMSC) to form a fibrocartilaginous joint surface, or cap, on top of a bony strut, similar to a costochondral rib graft (CCRG), which could be fixed to the mandibular ramus. This new approach to tissue engineering a TMJ would be advantageous because of its patient site-specific anatomical configuration as well as its potential ability to adapt to the loading forces placed on it during function.

Biocompatible Materials↗

An image-based approach for designing and manufacturing craniofacial scaffolds.

Bone tissue engineering (BTE), which combines biomaterial scaffolds with biologically active factors, holds tremendous promise for reconstructing craniofacial defects. A significant challenge in craniofacial reconstructive BTE applications is the complex patient-specific geometry that must be reconstructed. In this paper, we present an image-based approach for designing and manufacturing patient-specific craniofacial biomaterial scaffolds directly from CT or MRI data. In this approach, voxel density distribution is used to define scaffold topology. The scaffold design topology is created using image processing techniques. This voxel density distribution is then converted to data that can be used to drive a Solid Free-Form Fabrication machine to either directly build the scaffold or build a mold for the scaffold. Several preliminary applications for craniofacial surgery, including a mandibular condyle scaffold, an orbital floor scaffold, and a general mandibular defect scaffold, are illustrated. Finally, we show applications to in vivo models.

Animals↗

Development and characterization of a tissue-engineered human oral mucosa equivalent produced in a serum-free culture system.

A problem maxillofacial surgeons face is a lack of sufficient autogenous oral mucosa for reconstruction of the oral cavity. Split-thickness or oral mucosa grafts require more than one surgical procedure and can result in donor site morbidity. Skin has disadvantages of adnexal structures and a different keratinization pattern than oral mucosa. In this study, we successfully assembled, ex vivo, a human oral mucosa equivalent, consisting of epidermal and dermal components, in a defined, essential-fatty-acid-deficient, serum-free culture medium without a feeder layer, that could be used for intra-oral grafting in humans. Autogenous oral keratinocytes were seeded onto a cadaveric dermis, AlloDerm. The oral mucosa equivalent was cultured at an air-liquid interface for 2 wks. The resulting equivalent had a well-stratified parakeratinized epithelial layer similar to native oral keratinized mucosa. Expression of differentiation markers, filaggrin and cytokeratin 10/13, suggested a premature keratinized state. The presence of proliferation markers, proliferating cell nuclear antigen (PCNA) and Ki-67, suggested a state of hyperproliferation. Fatty acid composition of the equivalent was similar to that of in vitro cultured oral keratinocytes but differed from the that of in vivo native tissue, showing a lower content of 18:2 and 20:4, and a higher content of 16:1 and 18:1 fatty acids, respectively. The keratinocytes of the equivalent appeared to be in a more active and proliferative state than native keratinized mucosa. The dynamic nature of the cell population on the oral mucosa equivalent may be beneficial for intra-oral grafting procedures and for transfection of the keratinocytes.

Biomedical Engineering↗

[A tissue engineering approach to site-specific reconstruction of skeletal structures of the maxillofacial region:part I]

This article will present an image-based approach to design and manufacture of scaffolds for the tissue engineering of bone and cartilage constructs. Our vision of tissue-engineered bone and/or cartilage constructs utilizes 3-D designed and manufactured biodegradable scaffolds that are site specific for the area of maxillofacial reconstruction. The fabricated site-specific scaffold can be constructed such that it will impart biologic cues to implanted cells placed within its interstices. These biologic cues should influence scaffold implanted mesenchymal stem cells (MSC) or bone marrow stromal cells (BMSC) to form the necessary tissue for site specific facial reconstruction. This new approach to tissue engineering of the maxillofacial region would be advantageous because of its site-specific anatomical configuration as well as its potential ability to adapt to the functional forces placed on it during function. The reconstruction of the condylar-ramus area of the temporomandibular joint (TMJ) will be used as an illustration of this approach.

Journal Article↗

Ex vivo development of a composite human oral mucosal equivalent.

PURPOSE: The aim of this study was the ex vivo development of a composite oral mucosal equivalent composed of a continuous stratified layer of human oral keratinocytes grown on a cadaveric human dermal matrix in a defined medium without a feeder layer. MATERIALS AND METHODS: Enzymatically dissociated human oral keratinocytes from keratinized oral mucosa were cultured, submerged in a serum-free, low-calcium (0.15 mmol/L) supplemented medium, and expanded through several passages. Once a sufficient population of keratinocytes was reached, they were seeded on 1-cm2 pieces of AlloDerm (LifeCell Co, Woodlands, TX), an acellular nonimmunogenic cadaveric human dermis, at cell densities of 2.5 X 10(4), 5.0 X 10(4), 1.25 X 10(5), or 2.5 X 10(5). The oral keratinocyte-AlloDerm composites were cultured while submerged in a high-calcium (1.8 mmol/L) medium for 4 days. After 4 days, the composites were raised to an air-liquid interface. Samples of the composites were taken for histologic examination at 4, 11, and 18 days postseeding of the keratinocytes on the AlloDerm. RESULTS: At day 4, only the seeded cell density of 2.5 X 10(5) cells/cm2 formed a continuous monolayer on the AlloDerm. At day 11, a continuous stratified epithelium was seen, and at day 18 a well-differentiated, confluent parakeratotic epithelial layer was developed at cell densities of 5.0 X 10(4), 1.25 X 10(5), and 2.5 X 10(5)cells/cm2. CONCLUSION: With the method used, it was possible to successfully develop an ex vivo composite oral mucosal equivalent that consisted of a stratified epidermis on a dermal matrix.

Calcium↗

Primary synovial chondromatosis of the temporomandibular joint with suspected traumatic etiology. Report of a case.

Synovial chondromatosis (SC) of the temporomandibular joint (TMJ) is a rare disease that is characterized by the development of nodules of cartilage within the synovial connective tissues of articulating joints. Reports of extracapsular TMJ SC are rare. A case is presented of primary SC of the TMJ with extension to the pterygoid plates, with a suspected traumatic etiology. The differences between primary and secondary SC are discussed.

Adult↗

CT-generated porous hydroxyapatite orbital floor prosthesis as a prototype bioimplant.

Hydroxyapatite bioceramic was used for the manufacture of an orbital floor prosthesis from spiral CT data acquired transaxially at 1-mm beam collimation, pitch of 1, and 0.2-mm reconstruction intervals. CT data were converted to vector file format for subsequent prosthesis manufacture on a stereo-lithography machine. The orbital floor prosthesis was engrafted onto an acrylic model of the orbit as a qualitative indication of its overall accuracy. High anatomic accuracy was achieved, as determined by visual inspection. Cross-hatching of the vector file data allowed a porous internal architecture of the prosthesis. Refinements in chemical structure of the hydroxyapatite bioceramic are expected to enhance mechanical properties.

Child↗

Incidence of maxillofacial involvement in arthrogryposis multiplex congenita.

PURPOSE: This study determined the incidence of maxillofacial involvement in patients diagnosed with arthrogryposis multiplex congenita (AMC). PATIENTS AND METHODS: Twenty-three patients were evaluated by the pediatric physical medicine and rehabilitation, orthopedic surgery, and pediatric oral and maxillofacial surgery departments. Any patient in whom the diagnosis of AMC was in doubt was excluded from the study. All patients with limited mandibular function underwent computed tomography (CT) examination of their temporomandibular joints (TMJ). The results of physical therapy were followed. RESULTS: Five of the 23 patients diagnosed with AMC were found to have maxillofacial involvement, eg, presence of cleft palate, Robin-like sequence, high-arched palate, open-bite deformity, facial muscle weakness, esophageal dysfunction, and limited mandibular opening. No TMJ abnormalities were found by CT scan. Physical therapy was used for treatment of the limited opening, but relapse occurred quicky after therapy was discontinued. CONCLUSION: The incidence of maxillofacial findings is similar to that of most other reports. Treatment involves surgical correction of abnormal anatomy when possible (ie, cleft repair), symptomatic management (ie, esophageal dysfunction), and physical therapy.

Adolescent↗

Use of local tissues for temporomandibular joint surgery disc replacement.

The CTM flap offers the oral and maxillofacial surgeon an excellent graft material that can be used to replace, anatomically and functionally, a nonrestorable TMJ disc or failed alloplastic implant. It has numerous advantages over the existing autogenous, allogeneic, and alloplastic materials currently available. In addition, the anatomic location of the flap makes the logistics of harvesting the graft much easier.

Arthroplasty, Replacement↗

The use of a collagen sheet as a disc replacement in the rabbit temporomandibular joint.

PURPOSE: This study evaluated a biocompatible, preformed collagen sheet as a disc replacement after temporomandibular joint (TMJ) surgery in the rabbit and compared its performance with that of an autogenous dermal graft. MATERIALS AND METHODS: Twenty adult New Zealand white rabbits were divided into four groups of five animals: 1) nonoperated control; 2) TMJ discectomy without replacement; 3) discectomy with dermal graft replacement; and 4) discectomy with collagen sheet replacement. Each operated animal had the same procedure bilaterally. Rabbits were killed at 2, 4, 8, 18, and 36 weeks after surgery and the TMJs were surgically removed en bloc, decalcified, sectioned, and stained for histologic evaluation. RESULTS: There was significant articular destruction in the discectomized joints with no disc replacement. Both the dermal and collagen disc replacements were resorbed by the eighth week and the articular surfaces exhibited cartilaginous hyperplasia, which returned to near normal thickness by the 18th week. CONCLUSION: This study demonstrated that both a collagen sheet and a dermal graft may act in a protective capacity and may help retard early degenerative changes normally seen in the articular surfaces of discectomized TMJs.

Animals↗

In vitro comparison of parameters affecting the fixation strength of sagittal split osteotomies.

PURPOSE: The goal of this study was to determine how different parameters affect the bending strength of human cadaver mandibles that have undergone a sagittal split osteotomy. MATERIALS AND METHODS: The effects of screw material (titanium [Ti] vs polylactic acid/polyglycolic acid [PLA/PGA]), screw configuration (linear vs inverted L-shape), screw diameter (2.0 mm vs 2.7 mm), material into which screws were inserted (human mandible, bovine rib, synthetic polymer), and loading rate (1.0 mm/min vs 10.0 mm/min) were quantified. Also, biomechanical principles were used to model shear stress and displacement. Variable lever arms, screw material, screw diameter, screw configuration, distance between screws, and bone properties were all evaluated in this model. RESULTS: Accounting for variable mandible geometries and differentiating between deflections (and shear stresses) due to bending and due to torsion, in vitro mechanical testing revealed that there was a statistically significant difference in total shear stress at 3 mm of deflection depending on screw material (Ti > PLA/PGA), screw diameter, and material into which screws are inserted (mandibles > ribs = synthetic polymer). There was no significant difference in total shear stress depending on screw configuration or strain rate. CONCLUSION: Total shear stress and deflections are important and more viable parameters than load to assess parameters of clinical importance in osteotomy or fracture fixation.

Aged↗