Biomedical subjects

J J Mao

Publications and source records attributed to J J Mao.

14 recordsLinked to original sources

PubMed2006

Craniofacial tissue engineering by stem cells.

Craniofacial tissue engineering promises the regeneration or de novo formation of dental, oral, and craniofacial structures lost to congenital anomalies, trauma, and diseases. Virtually all craniofacial structures are derivatives of mesenchymal cells. Mesenchymal stem cells are the offspring of mesenchymal cells following asymmetrical division, and reside in various craniofacial structures in the adult. Cells with characteristics of adult stem cells have been isolated from the dental pulp, the deciduous tooth, and the periodontium. Several craniofacial structures--such as the mandibular condyle, calvarial bone, cranial suture, and subcutaneous adipose tissue--have been engineered from mesenchymal stem cells, growth factor, and/or gene therapy approaches. As a departure from the reliance of current clinical practice on durable materials such as amalgam, composites, and metallic alloys, biological therapies utilize mesenchymal stem cells, delivered or internally recruited, to generate craniofacial structures in temporary scaffolding biomaterials. Craniofacial tissue engineering is likely to be realized in the foreseeable future, and represents an opportunity that dentistry cannot afford to miss.

Absorbable Implants↗

PubMed2004

Nanomechanical properties of facial sutures and sutural mineralization front.

The mechanical properties of craniofacial sutures have rarely been investigated. Three facial sutures-the pre-maxillomaxillary (PMS), the nasofrontal (NFS), and the zygomaticotemporal (ZTS)-and their corresponding sutural mineralization fronts in 8 young New Zealand White rabbits were subjected to nano-indentation with atomic force microscopy as a test of the hypothesis that they have different mechanical properties. The average elastic modulus of the PMS was 1.46 +/- 0.24 MPa (mean +/- SD), significantly higher than both the ZTS (1.20 +/- 0.20) and NFS (1.16 +/- 0.18). The average elastic moduli of sutural mineralization fronts 30 micro m away were significantly higher than their corresponding sutures and had the same distribution pattern: the PMS (2.07 +/- 0.24 MPa) significantly higher than both the ZTS (1.56 +/- 0.29) and NFS (1.71 +/- 0.22). Analysis of these data suggests that facial sutures and their immediately adjacent sutural mineralization fronts have different capacities for mechanical deformation. The elastic properties of sutures and sutural mineralization fronts are potentially useful for improving our understanding of their roles in development.

Analysis of Variance↗

PubMed2004

Tissue-engineered rabbit cranial suture from autologous fibroblasts and BMP2.

Craniosynostosis is a congenital disorder of premature ossification of cranial sutures, occurring in one of approximately every 2500 live human births. This work addressed a hypothesis that a cranial suture can be tissue-engineered from autologous cells. Dermal fibroblasts were isolated subcutaneously from growing rabbits, culture-expanded, and seeded in a gelatin scaffold. We fabricated a composite tissue construct by sandwiching the fibroblast-seeded gelatin scaffold between two collagen sponges loaded with recombinant human BMP2. Surgically created, full-thickness parietal defects were filled with the composite tissue construct in the same rabbits from which dermal fibroblasts had been obtained. After four-week in vivo implantation, there was de novo formation of tissue-engineered cranial suture, microscopically reminiscent of the adjacent natural cranial suture. The tissue-engineered cranial suture showed radiolucency on radiographic images, in contrast to radio-opacity of microscopically ossified calvarial defects filled with fibroblast-free, BMP2-loaded constructs. This approach may be refined for tissue engineering of cranial sutures for craniosynostosis patients.

Analysis of Variance↗

PubMed2003

Tissue-engineered neogenesis of human-shaped mandibular condyle from rat mesenchymal stem cells.

The temporomandibular joint is susceptible to diseases and trauma that may ultimately lead to structural degeneration. Current approaches for replacing degenerated mandibular condyles suffer from deficiencies such as donor site morbidity, immunorejection, implant wear and tear, and pathogen transmission. The hypothesis of this study was that a human-shaped mandibular condyle can be tissue-engineered from rat mesenchymal stem cells (MSCs) encapsulated in a biocompatible polymer. Rat bone marrow MSCs were isolated and induced to differentiate into chondrogenic and osteogenic cells in vitro, and encapsulated in poly(ethylene glycol)-based hydrogel in two stratified layers molded into the shape of a cadaver human mandibular condyle. Eight weeks following in vivo implantation of the bilayered osteochondral constructs in the dorsum of immunodeficient mice, mandibular condyles formed de novo. Microscopic evaluation of the tissue-engineered mandibular condyle demonstrated two stratified layers of histogenesis of cartilaginous and osseous phenotypes. The current approach is being refined for ultimate therapeutic applications.

Animals↗

PubMed2002

Bone strain patterns of the zygomatic complex in response to simulated orthopedic forces.

Craniofacial bone strain upon orthopedic loading has rarely been characterized, despite its fundamental importance in our understanding of the anabolic and catabolic effects of orthopedic forces. The present study tested the hypothesis that zygomatic bone strain is modulated upon loading by headgear, a device widely used in craniofacial orthopedics. Ramp forces from 0 to 50 Newtons were applied via headgear attached to the permanent maxillary first molars in four juvenile and five adult human skulls. The average peak bone strain of the juvenile temporal articular eminence was significantly higher than the adult articular eminence (p < 0.05). Contrasting bone strain patterns were identified in the zygomatic arch: tensile in its lateral surface but compressive in its medial surface. The peak bone strain of the temporal articular eminence and the zygomatic arch both depend upon loading direction. Thus, headgear-generated orthopedic forces evoke bending of the zygomatic arch and stresses of the temporal articular eminence in vitro, suggesting the need to verify whether bone strain induces in vivo bone modeling and remodeling.

Adolescent↗

PubMed2002

Chondrocyte proliferation of the cranial base cartilage upon in vivo mechanical stresses.

Whereas the growth of the cranial base cartilage is thought to be regulated solely by genes, epiphyseal growth plates are known to respond to mechanical stresses. This disparity has led to our hypothesis that chondrocyte proliferation is accelerated by mechanical stimuli above natural growth. Two-Newton tensile forces with static and cyclic waveforms were delivered in vivo to the premaxillae of actively growing rabbits for 20 min/day over 12 consecutive days. The average number of BrdU-labeled chondrocytes in the proliferating zone treated with cyclic forces was significantly higher than both static forces of matching peak magnitude and sham controls representing natural chondral growth. Cyclic forces also evoked greater area of the proliferating zone than both static forces and sham controls. Thus, chondrocyte proliferation is enhanced by mechanical stresses in vivo, especially those with oscillatory waveform. Analysis of these data suggests that genetically coded chondral growth is up-regulated by mechanical signals.

Analysis of Variance↗

PubMed2002

Mechanobiology of craniofacial sutures.

Craniofacial sutures are soft connective-tissue joints between mineralized skull bones. Suture mechanobiology refers to the understanding of how mechanical stimuli modulate sutural growth. This review's hypothesis is that novel mechanical stimuli can effectively modulate sutural growth. Exogenous forces with static, sinusoidal, and square waveforms induce corresponding waveforms of sutural strain. Sutural growth is accelerated upon small doses of oscillatory strain, as few as 600 cycles delivered 10 min/day over 12 days. Interestingly, both oscillatory tensile and compressive strains induce anabolic sutural responses beyond natural growth. Mechanistically, oscillatory strain likely turns on genes and transcription factors that activate cellular machinery via mechanotransduction pathways. Thus, sutural growth is determined by hereditary and mechanical signals via the common pathway of genes. It is concluded that small doses of oscillatory mechanical stimuli have the potential to modulate sutural growth effectively: either accelerating it or initiating net sutural bone resorption for various therapeutic objectives.

Animals↗

PubMed2001

Regional structural and viscoelastic properties of fibrocartilage upon dynamic nanoindentation of the articular condyle.

Fibrocartilage,a tissue with macromaterial properties between dense fibrous tissue and hyaline cartilage, is not well understood in its ultrastructure and regional viscoelastic properties. Here nanoindentation with atomic force microscopy was performed on fresh fibrocartilage samples of rabbit jaw joint condyles. Each sample was divided into anteromedial, anterolateral, posteromedial, and posterolateral regions for probing and topographic imaging in 2 x 2 microm and 10 x 10 microm scan sizes. Young's moduli differed significantly among these regions in a descending gradient from the anteromedial (2.34 +/- 0.26 MPa) to the posterolateral (0.95 +/- 0.06 MPa). The Poisson ratio, defined as lateral strain over axial strain, had the same gradient distribution: highest for the anteromedial region (0.46 +/- 0.05) and lowest for the posterolateral region (0.31 +/- 0.05). The same four regions showed a descending gradient of surface roughness: highest for the anteromedial (321.6 +/- 13.8 nm) and lowest for the posterolateral (155.6 +/- 12.6 nm). Thus, the regional ultrastructural and viscoelastic properties of fibrocartilage appear to be coregulated. Based on these region-specific gradient distributions, fibrocartilage is constructed to withstand tissue-borne shear stresses, which likely propagate across its different regions. A model of shear gradient and concentric gradient is proposed to describe the region-specific capacity of fibrocartilage to sustain shear stresses in tendons, ligaments, joints, and the healing bone across species.

Animals↗

PubMed2001

The relationship between alphaB-crystallin and neurofibrillary tangles in Alzheimer's disease.

AlphaB-crystallin is known as a small heat shock protein with a cytoprotective function. This study was undertaken to investigate the relationship between alphaB-crystallin and changes seen in Alzheimer's disease. The distribution and immunohistochemical characteristics of alphaB-crystallin positive neurones in the cerebral cortices of 4 patients with Alzheimer's disease were examined. AlphaB-crystallin positive neurones were mainly distributed in the limbic and paralimbic regions, namely parahippocampal gyrus, fusiform gyrus, cingulate cortex, middle and superior frontal gyrus, and insular cortex, which corresponded to commonly affected regions in Alzheimer's disease. Moreover, such neurones were present predominantly in the III or V layer of the cerebral cortex. The number of alphaB-crystallin positive neurones increased in parallel with the neuronal loss. Logistic regression analysis revealed a significant relation between the density of alphaB-crystallin positive neurones and that of extracellular neurofibrillary tangles (NFTs), with a correlation coefficient (r) of 0.57 and P < 0.0001 in 14 regions of the cerebral cortex. In contrast, the relation was not statistically significant between the density of alphaB-crystallin positive neurones and that of classical senile plaques, diffuse plaques or intracellular NFTs. Modified Gallyas-Braak (GB) staining on alphaB-crystallin positive neurone demonstrated several patterns of the structures: faint GB positive structures in the swollen perikaryon with straight neurites, fine granules compressed and contorted into fuzzy bundles, intensely GB positive filamentous structures together with fine granules and very intensely GB positive ring-like NFTs in a swollen perikaryon with curved neurites. In positive neurones, the density of ring-like NFTs correlated with that of atrophic perikaryon, or bent neurites and a decrease in the immunoreactivity of alphaB-crystallin. These data suggest that a close relationship exists between the appearance of alphaB-crystallin in neurones, extracellular NFTs, and neurofibrillary formation in alphaB-crystallin positive neurones in Alzheimer brain.

Aged↗

PubMed2000

Gallyas-positive argyrophilic and ubiquitinated filamentous inclusions in rapidly progressive motor neuron disease: immunohistochemical and electron microscopic studies.

In an autopsy case of sporadic rapidly progressive lower motor neuron disease (MND), Gallyas-positive argyrophilic and ubiquitinated filamentous intracytoplasmic inclusions were found in the neurons. Clinically, 7 months prior to death, a 68-year-old woman experienced a history of rapidly progressive muscle weakness of all four extremities and bulbar sign, without sensory and autonomic disturbance. Two months later, she became unable to stand or walk. Four months after onset, she needed respiratory support, and subsequently died due to cardiorespiratory arrest. Neuropathological examinations revealed neuronal loss and associated gliosis in the lower motor neurons, except for ocular motor nuclei, Clark's column, and accessory cuneate nucleus, and tract degeneration was observed in the middle root zone of the posterior column and spinocerebellar tract. No Bunina bodies or Lewy body-like hyaline inclusions were found in the anterior horns. Gallyaspositive argyrophilic filamentous inclusions were found in the lower motor neurons and in nerve cells of the Clark's column, intermediate zone, posterior horn and accessory cuneate nucleus. These were positive with anti-ubiquitin antibody but negative with anti-tau (tau-2 and AT8) and neurofilament antibodies. Electron microscopic examinations disclosed randomly arranged tubular-like filamentous profiles, with a diameter of 12-14 nm, sometimes with amorphous granules in the perikaryon. This is the first report on the Gallyas-positive argyrophilic and ubiquitinated filamentous inclusions in neurons in MND.

Aged↗

PubMed1998

Slowly progressive L-DOPA nonresponsive pure akinesia due to nigropallidal degeneration: a clinicopathological case study.

We report an autopsy case of a 51-year old man who showed slowly progressive pure akinesia: freezing phenomenon and festination during 21 years of illness without tremor, rigidity, upward gaze palsy, bradykinesia and dementia, which were not responded to L-DOPA clinically. Neuropathological findings revealed the circumscribed regions in the substantia nigra and middle portion of the internal globus pallidus (GPi), without neurofibrillary tangles, neuropil threads, and glial fibrillary tangles. So this case was clearly distinguished with progressive nuclear palsy and pallidonigroluisian atrophy. It was first reported to describe that L-DOPA nonresponsive pure akinesia can arise from nigopallidal atrophy.

Disease Progression↗

PubMed1998

Argyrophilic structures stimulate glial reactions in neurofibrillary tangles and senile plaques.

Neurofibrillary tangles (NFT) and senile plaques (SP) contain various pathological structures, and the majority of these pathological structures are argyrophilic. To investigate the glial reactions of the argyrophilic substance, we performed immunohistochemistry for microglia or for astroglia after Gallyas-Braak staining, which is one of the most sensitive silver impregnation techniques detecting argyrophilic structures in NFT and SP. We found that extracellular argyrophilic structures in NFT and SP showed glial reactions, and we observed reactive microglia in the center of NFT and SP in contrast to astroglia, which were situated in the periphery. These findings suggest that the exposed argyrophilic components in the extracellular space stimulate both glial reactions, but that there is a striking difference in localization between microglia and astroglia.

Alzheimer Disease↗

PubMed1998

Proteoglycan expression in the rat temporomandibular joint in response to unilateral bite raise.

The vertebrate articular tissue consists of collagen fibers embedded in a ground substance. Collagen resists tensile forces, while proteoglycans in the ground substance provide resilience and resistance to compression. It was hypothesized that unilateral bite raise would induce increasing expression of proteoglycans in TMJ articular tissues. As a test of this hypothesis, six- and nine-week-old Sprague-Dawley rats received unilateral bite-raising appliances bonded to their right upper molars for 4 wks. A group of nine-week-old rats was housed for an additional 4 wks after removal of the appliances they had worn for 4 wks. Proteoglycans that carry abundant chondroitin sulfate and keratan sulfate side-chains, most likely aggrecans, were detected by safranin O in the fibrocartilaginous zone of the condyle in parasagittal sections. A monoclonal antibody against a large chondroitin sulfate proteoglycan related to versican reacted strongly in the surface fibrous layer of the mandibular condyle and moderately in the discs of the treated specimens. Computer quantification for safranin O and anti-versican antibody staining revealed that the average intensities of the treated specimens were significantly higher than those of their corresponding sham-operated controls, and the average intensities of the treatment-reversal specimens had no significant differences from their corresponding sham-operated controls. Thus, unilateral bite raise appeared to have induced an increase in the expression of aggrecan in the condylar cartilage and a proteoglycan related to versican in the TMJ disc and the articular surface of the condyle. The elevated proteoglycan expression is interpreted to suggest that unilateral bite raise leads to an increase in the magnitude of compressive forces in the rat temporomandibular joint.

Aggrecans↗

PubMed1996

Coupling electrical and mechanical outputs of human jaw muscles undertaking multidirectional bite-force tasks.

Previous studies have identified both linear and curvilinear relations between increasing bite-force magnitude and the integrated electromyogram (EMG) of jaw-closing muscles. In an attempt to explain the discrepancy, bite forces of incrementally increasing magnitude were produced on the right-hand side in five specified directions by eight humans. Linear regression lines were fitted to normalized EMG activities of the left and right masseter and temporalis muscles against increasing bite-force magnitude in each direction. The grand mean of linear correlation coefficients was 0.79 (+/- 0.11 SD), suggesting an overall linear relation. Each set of individual data was fitted with polynomial lines up to the third order. The best fit was selected by statistical significance of coefficients and the least-square analysis of the sum of residues for each fitted line; 62% of individual data-sets were best fitted with linear regression lines, 31% with quadratic lines and the remaining 7% with cubic lines. Repeated analysis of residue variance of the pooled data showed that either a linear or quadratic line fitted every data set except one, for which a cubic line had the best fit. Working-side muscles had significantly larger linear correlation coefficients than corresponding balancing-side muscles for most bite-force directions. Analysis of variance of linear correlation coefficients revealed that the degree of linearity often depended upon the roles played by a muscle in producing forces in different directions. It appears that linearity or non-linearity of the EMG force relation is a determinant, among other variables, of the direction of the resultant force.

Adult↗