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Biomedical subjects

Jeremy J Mao

Publications and source records attributed to Jeremy J Mao.

At least 19 recordsLinked to original sources
PubMed2006

Continuing differentiation of human mesenchymal stem cells and induced chondrogenic and osteogenic lineages in electrospun PLGA nanofiber scaffold.

Nanofibers have recently gained substantial interest for potential applications in tissue engineering. The objective of this study was to determine whether electrospun nanofibers accommodate the viability, growth, and differentiation of human mesenchymal stem cells (hMSCs) as well as their osteogenic (hMSC-Ob) and chondrogenic (hMSC-Ch) derivatives. Poly(d,l-lactide-co-glycolide) (PLGA) beads with a PLA:PGA ratio of 85:15 were electrospun into non-woven fibers with an average diameter of 760+/-210 nm. The average Young's modulus of electrospun PLGA nanofibers was 42+/-26 kPa, per nanoindentation with atomic force microscopy (AFM). Human MSCs were seeded 1-4 weeks at a density of 2 x 10(6)cells/mL in PLGA nanofiber sheets. After 2 week culture on PLGA nanofiber scaffold, hMSCs remained as precursors upon immunoblotting with hKL12 antibody. SEM taken up to 7 days after cell seeding revealed that hMSCs, hMSC-Ob and hMSC-Ch apparently attached to PLGA nanofibers. The overwhelming majority of hMSCs was viable and proliferating in PLGA nanofiber scaffolds up to the tested 14 days, as assayed live/dead tests, DNA assay and BrdU. In a separate experiment, hMSCs seeded in PLGA nanofiber scaffolds were differentiated into chodrogenic and osteogenic cells. Histological assays revealed that hMSCs continuously differentiated into chondrogenic cells and osteogenic cells after 2 week incubation in PLGA nanofibers. Taken together, these data represent an original investigation of continuous differentiation of hMSCs into chondrogenic and osteogenic cells in PLGA nanofiber scaffold. Consistent with previous work, these findings also suggest that nanofibers may serve as accommodative milieu for not only hMSCs, but also as a 3D carrier vehicle for lineage specific cells.

Biocompatible Materials↗
PubMed2006

Comparison of osteogenic potentials of visceral and subcutaneous adipose-derived cells of rabbits.

BACKGROUND: The demand for a large amount of osteogenic cells required in bone tissue engineering warranted exploration of a new source of osteoprogenitor cells. Recent studies have demonstrated that adipose-derived stromal cells possess multiple differentiation capacities, including osteogenic potential, as bone marrow mesenchymal stem cells. In the present study, the authors compared the osteogenic potentials of adipose-derived stromal cells from different anatomical sites of rabbits. METHODS: Different adipose-derived stromal cells were isolated from rabbit visceral and subcutaneous adipose tissues by enzymatic digestion and in vitro differentiation into osteogenic lineage. Osteogenic markers representing differentiation potentials of adipose-derived stromal cells from different anatomical sites were compared by biochemical and immunohistochemical assessment (n = 3). RESULTS: Fibroblast-like cells were digested from both visceral and subcutaneous adipose tissues. After exposure to osteogenic differentiation medium, visceral adipose-derived cells were found to possess greater osteogenic potentials than cells isolated from subcutaneous adipose tissues, evidenced by significantly different amounts of osteogenic markers including alkaline phosphatase, osteocalcin, and mineral deposition. CONCLUSION: This study indicates that osteogenic potentials of adipose-derived cells vary by their anatomical sites, with visceral adipose-derived cells exhibiting higher osteogenic potential than those isolated from subcutis. However, the mechanism is still unidentified.

Animals↗
PubMed2006

Matrix and gene expression in the rat cranial base growth plate.

Recent data have shown that the proliferation and differentiation of the cranial base growth plate (CBGP) chondrocytes are modulated by mechanical stresses. However, little is known about the expression of genes and matrix molecules in the CBGP during development or under mechanical stresses. The objective of the present study was to determine whether several cartilage- and bone-related molecules are expressed in the CBGP and whether their expression is modulated by cyclic loading. The CBGP of normal 8-day-old rats (n=8) were isolated immediately after death, followed by extraction of total RNA and reverse transcription/polymerase chain reaction (RT-PCR) analysis. All studied genes, including type II and X collagens, biglycan, versican, osteocalcin, osteopontin, and fetal liver kinase 1, were expressed in the CBGP with a reproducible absence of decorin mRNA. In age- and sex-matched rats (n=10), exogenous cyclic forces were applied to the maxilla at 500 mN and 4 Hz for 20 min/day over 2 days, followed by RNA isolation and RT-PCR analysis. This exogenous cyclic loading consistently induced the expression of the decorin gene, which was non-detectable, by the current RT-PCR approach, in control neonatal CBGPs without loading. Immunolocalization of several of the above-studied gene products demonstrated their remarkable site-specific expression. Decorin proteoglycan was primarily expressed in the perichondrium instead of various cartilage growth zones, especially upon mechanical loading. These findings serve as baseline data for the expression of several genes and gene products in the neonatal CBGP. Mechanical modulation of decorin expression is consistent with recent reports of its susceptibility to mechanical loading in several connective tissues.

Animals↗
PubMed2006

Geometry and cell density of rat craniofacial sutures during early postnatal development and upon in vivo cyclic loading.

Cranial sutures are unique to skull bones and consist of multiple connective tissue cell lineages such as mesenchymal cells, fibroblast-like cells, and osteogenic cells, in addition to osteoclasts. Mechanical modulation of intramembranous bone growth in the craniofacial suture is not well understood, especially during postnatal development. This study investigated whether in vivo mechanical forces regulate sutural growth responses in postnatal rats. Cyclic compressive forces with a peak-to-peak magnitude of 300 mN and 4 Hz were applied to the maxilla in each of 17-, 23-and 32-day-old rats for 20 min/day over 5 consecutive days. Computerized histomorphometric analysis revealed that cyclic loading significantly increased the average geometric widths of the premaxillomaxillary suture (PMS) to 86 +/- 7 microm, 99 +/- 12 microm, and 149 +/- 30 microm, representing 32%, 50%, and 39% increases for P17, P23, and P32 in comparison with age-matched sham controls. For the nasofrontal suture (NFS), cyclic loading significantly increased the average sutural widths to 88 +/- 15 microm, 92 +/- 10 microm, and 100 +/- 14 microm, representing 33%, 24%, and 32% increases for P17, P23, and P32 relative to age-matched controls. The average PMS cell density upon cyclic loading was 10182 +/- 132 cells/mm(2), 9752 +/- 661 cells/mm(2), and 9521 +/- 628 cells/mm(2), representing 62%, 35%, and 30% increases for P17, P23, and P32 in comparison with age-matched controls. For the NFS, cyclic loading increased the average cell density to 9884 +/- 893 cells/mm(2), 9818 +/- 1091 cells/mm(2), 9355 +/- 661 cells/mm(2), representing 44%, 46% and 40% increases at P17, P23, and P32 respectively. Osteoblast-occupied sutural bone surface was significantly greater in cyclically loaded sutures for P17, P23, and P32 than corresponding controls for both the PMS and NFS. On the other hand, cyclic loading elicited significantly higher sutural bone surface populated by osteoclast-like cells by P17 and P23 days, but not P32 days, for the PMS. For the NFS, sutural osteoclast surface was significantly higher upon cyclic loading for P23 and P32 days, but not P17. The present data demonstrate that cyclic forces are potent stimuli for modulating postnatal sutural development, potentially by stimulating both osteogenesis and osteoclastogenesis. Cyclic loading may have clinical implications as novel mechanical stimuli for modulating craniofacial growth in patients suffering from craniofacial anomalies and dentofacial deformities.

Animals↗
PubMed2006

Modulation of endochondral development of the distal femoral condyle by mechanical loading.

Although previous theoretical modeling studies have predicted that various mechanical stresses accelerate or inhibit the ossification process of the neonatal chondroepiphysis, there is a paucity of experimental data to verify these models. The present study was designed to provide experimental evidence on whether the ossification of the chondroepiphysis is modulated by mechanical loading on the distal femoral condyle explant of the neonatal (5-day-old) rabbit in organ culture. Upon aseptic dissection, the right condyle explant was immersed in and fixated to an organ culture system, and received cyclic forces at 200 mN and 1 Hz for 12 h (N=8) directly on its slightly convex articular surface, whereas the contralateral, left condyle explant was immersed separately in organ culture (N=8). Subsequently, both loaded and control explants were placed in a bioreactor rotating at 20 rpm for 72 h. In each mechanically loaded specimen, a structure reminiscent of the secondary ossification center (SOC) appeared with an average area of 1.17+/-0.13 mm(2), or 15.2+/-8.2% of the total epiphysis area. In contrast, no SOC was detected in any of the unloaded contralateral control specimens. The SOC in mechanically loaded specimens was stained intensively with fast green, whereas either the rest of the loaded epiphysis or the entire control epiphysis was stained intensely to safranin-O but lacked fast green staining. Immunolocalization revealed that the SOC of the mechanically loaded specimens expressed Run x 2 and osteopontin, both of which were absent in the unloaded control specimens. Type X collagen was expressed surrounding hypertrophic chondrocytes adjacent to the SOC, but was absent in the control specimen. Type II collagen and decorin were absent in the SOC of the loaded specimen, but were expressed throughout the rest of the loaded epiphysis and the unloaded control epiphysis. The intensity of type II collagen and decorin expression was significantly stronger among hypertrophic chondrocytes surrounding the SOC than the control. The numbers of hypertrophic chondrocytes surrounding the SOC and superior to metaphyseal bone were significantly higher in the loaded specimens than the unloaded controls. Taken together, mechanical stresses accelerate the formation of the secondary ossification center, and therefore modulate endochondral ossification.

Animals↗
PubMed2006

Mesenchymal stem cells and tissue engineering.

Mesenchymal stem cells (MSCs) have become one of the most studied stem cells, especially toward the healing of diseased and damaged tissues and organs. MSCs can be readily isolated from a number of adult tissues by means of minimally invasive approaches. MSCs are capable of self-replication to many passages and, therefore, can potentially be expanded to sufficient numbers for tissue and organ regeneration. MSCs are able to differentiate into multiple cell lineages that resemble osteoblasts, chondrocytes, myoblasts, adipocytes, and fibroblasts and express some of the key markers typical of endothelial cells, neuron-like cells, and cardiomyocytes. MSCs have been used alone for cell delivery or seeded in biomaterial scaffolds toward the healing of tissue and organ defects. After an increasing number of the "proof of concept" studies, the remaining tasks are many, such as to determine MSC interactions with host cells and signaling molecules, to investigate the interplay between MSCs and biological scaffold materials, and to apply MSC-based therapies toward clinically relevant defect models. The ultimate goal of MSC-based therapies has valid biological rationale in that clusters of MSCs differentiate to form virtually all connective tissue during development. MSC-based therapies can only be realized our improved understanding of not only their fundamental properties such as population doubling and differentiation pathways but also translational studies that use MSCs in the de novo formation and/or regeneration of diseased or damaged tissues and organs.

Adipogenesis↗
PubMed2006

Sustained release of TGFbeta3 from PLGA microspheres and its effect on early osteogenic differentiation of human mesenchymal stem cells.

Despite the widespread role of transforming growth factor-beta3 (TGFbeta3) in wound healing and tissue regeneration, its long-term controlled release has not been demonstrated. Here, we report microencapsulation of TGFbeta3 in poly-d-l-lactic-co-glycolic acid (PLGA) microspheres and determine its bioactivity. The release profiles of PLGA-encapsulated TGFbeta3 with 50:50 and 75:25 PLA:PGA ratios differed throughout the experimental period. To compare sterilization modalities of microspheres, bFGF was encapsulated in 50:50 PLGA microspheres and subjected to ethylene oxide (EO) gas, radio-frequency glow discharge (RFGD), or ultraviolet (UV) light. The release of bFGF was significantly attenuated by UV light, but not significantly altered by either EO or RFGD. To verify its bioactivity, TGFbeta3 (1.35 ng/mL) was control-released to the culture of human mesenchymal stem cells (hMSC) under induced osteogenic differentiation. Alkaline phosphatase staining intensity was markedly reduced 1 week after exposing hMSC-derived osteogenic cells to TGFbeta3. This was confirmed by lower alkaline phosphatase activity (2.25 +/- 0.57 mU/mL/ng DNA) than controls (TGFbeta3- free) at 5.8 +/- 0.9 mU/mL/ng DNA (p < 0.05). Control-released TGFbeta3 bioactivity was further confirmed by lack of significant differences in alkaline phosphatase upon direct addition of 1.35 ng/mL TGFbeta3 to cell culture (p > 0.05). These findings provide baseline data for potential uses of microencapsulated TGFbeta3 in wound healing and tissue-engineering applications.

Alkaline Phosphatase↗
PubMed2006

Nanostructural and nanomechanical properties of synostosed postnatal human cranial sutures.

Craniosynostosis represents a heterogeneous cluster of congenital disorders and manifests as premature ossification of one or more cranial sutures. Cranial sutures serve to enable calvarial growth and function as joints between skull bones. The mechanical properties of synostosed cranial sutures are of vital importance to their function and yet are poorly understood. The present study was designed to characterize the nanostructural and nanomechanical properties of synostosed postnatal sagittal and metopic sutures. Synostosed postnatal sagittal sutures (n = 5) and metopic sutures (n = 5) were obtained from craniosynostosis patients (aged 9.1 +/- 2.8 months). The synostosed sutural samples were prepared for imaging and indentation on both the endocranial and ectocranial surfaces with the cantilever probe of an atomic force microscopy. Analysis of the nanotopographic images indicated robust variations in sutural surface characteristics with localized peaks and valleys. In 5 x 5 mum scan sizes, the surface roughness of the synostosed metopic suture was significantly greater (223.6 +/- 93.3 nm) than the synostosed sagittal suture (142.9 +/- 80.3 nm) (P < 0.01). The Young's modulus of the synostosed sagittal suture at 0.7 +/- 0.2 MPa was significantly higher than the synostosed metopic suture at 0.5 +/- 0.1 MPa (P < 0.01). These data suggest that various synostosed cranial sutures may have different structural and mechanical characteristics.

Biomechanical Phenomena↗
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↗
PubMed2005

Expression and mechanical modulation of matrix metalloproteinase-1 and -2 genes in facial and cranial sutures.

Craniofacial sutures create a soft tissue interface between various calvarial and facial bones. Facial and cranial sutures show differences in their surrounding anatomical structures and local mechanical strain environments. Despite previous attempts to identify the expression of matrix metalloproteinase genes (MMPs) in cranial sutures, little is known regarding whether facial and cranial sutures differ in MMP expression. We have investigated the expression of MMP-1 and MMP-2 in the pre-maxillomaxillary suture (PMS; facial suture) and the frontoparietal suture (FPS; cranial suture) in 32-day-old rats with or without the application of cyclic loading. Expression of MMP-1 and MMP-2 was detected by the reverse transcription/polymerase chain reaction technique. At 32 days of postnatal development (n=6), both MMP-1 and MMP-2 were reproducibly expressed in the facial PMS, in comparison with negligible MMP-1 and MMP-2 expression in the cranial FPS. In six age- and sex-matched control rats, cyclic loading at 4 Hz and 1000 mN was applied to the maxilla for two 20-min episodes within a 12-h interval. In some (but not all) cases, cyclic loading induced marked expression of MMP-1 and MMP-2 in the PMS and FPS in comparison with corresponding non-loaded controls. These data confirm our previous finding that short doses of cyclic loading upregulate MMP-2 expression in craniofacial sutures and suggest the possibility that facial and cranial sutures differ in matrix degradation rates during postnatal development.

Animals↗
PubMed2005

Modulation of bone ingrowth of rabbit femur titanium implants by in vivo axial micromechanical loading.

Titanium implants commonly used in orthopedics and dentistry integrate into host bone by a complex and coordinated process. Despite increasingly well illustrated molecular healing processes, mechanical modulation of implant bone ingrowth is poorly understood. The objective of the present study was to determine whether micromechanical forces applied axially to titanium implants modulate bone ingrowth surrounding intraosseous titanium implants. We hypothesized that small doses of micromechanical forces delivered daily to the bone-implant interface enhance implant bone ingrowth. Small titanium implants were placed transcortically in the lateral aspect of the proximal femur in 15 New Zealand White rabbits under general anesthesia and allowed to integrate with the surrounding bone for 6 wk. Micromechanical forces at 200 mN and 1 Hz were delivered axially to the right femur implants for 10 min/day over 12 consecutive days, whereas the left femur implants served as controls. The average bone volume 1 mm from mechanically loaded implants (n = 15) was 73 +/- 12%, which was significantly greater than the average bone volume (52 +/- 21%) of the contralateral controls (n = 15) (P < 0.01). The average number of osteoblast-like cells per endocortical bone surface was 55 +/- 8 cells/mm(2) for mechanically loaded implants, which was significantly greater than the contralateral controls (35 +/- 6 cells/mm(2)) (P < 0.01). Dynamic histomorphometry showed a significant increase in mineral apposition rate and bone-formation rate of mechanically stressed implants (3.8 +/- 1.2 microm/day and 2.4 +/- 1.0 microm(3).microm(-2).day(-1), respectively) than contralateral controls (2.2 +/- 0.92 microm/day and 1.2 +/- 0.60 microm(3).microm(-2).day(-1), respectively; P < 0.01). Collectively, these data suggest that micromechanical forces delivered axially on intraosseous titanium implants may have anabolic effects on implant bone ingrowth.

Animals↗
PubMed2005

Ex vivo adipose tissue engineering by human marrow stromal cell seeded gelatin sponge.

The limitation of current clinical treatment for restoration extended defects of soft tissue associated with trauma, tumor resections, and congenital deformities are well known. This study demonstrates that human bone marrow stromal cells (MSCs) can be utilized to tissue engineer adipose tissue for therapeutic purposes. Adipogenic potentials of monolayer-cultured human MSCs were evaluated by biochemical measurement of an adipogenic differentiation marker (glycerol-3-phosphate dehydrogenase, G-3-PDH) and cellular morphology. After preparation by seeding human MSCs on a 3-dimensional gelatin sponge and exposure to adipogenic differentiation medium, the ex vivo tissue-engineered adipose constructs were assessed histomorphologically and biochemically. Lipid droplets accumulated and expanded within the constructs accompanied by a significant increase of G-3-PDH activity. The present study indicates that bone MSCs could be a cell resource in tissue engineering adipose tissue, while gelatin sponge could be a good scaffold in this approach to improve the outcome of clinical treatment.

Adipose Tissue↗
PubMed2005

Expression of matrix metalloproteinase genes in the rat intramembranous bone during postnatal growth and upon mechanical stresses.

A cranial suture consists of neural-crest derived cells and matrices between mineralized skull bones. Little is known regarding the involvement of matrix metalloproteinases (MMPs) in the degradation of extracellular matrix of cranial sutures. In the postnatal rat model, the posterior frontal suture (PFS) undergoes complete ossification between P12-P22, whereas the sagittal suture (SS) remains patent. The present study utilized reverse transcriptase-polymerase chain reaction (RT-PCR) to explore the expression of MMP-1 and MMP-2 genes in the PFS and SS in P8 and P32 rats, and also to determine whether these MMP genes are modulated by exogenous mechanical forces. RNA was isolated from P8 and P32 normal PFS and SS each by pooling sutural specimens from 14 to 20 rats. RT-PCR analysis and semi-quantitative luminosity demonstrated the expression of MMP-1 and MMP-2 genes in the patent P8 PFS, P8 SS, and P32 SS, but no apparent MMP-2 expression in the physiologically ossified P32 PFS. Exogenous cyclic forces applied to the maxilla at 1000 mN and 4 Hz elicited corresponding cyclic bone strain waveforms with peak strain of 134.14+/-38.15 muepsilon (mean+/-S.D.) for the PFS, and 28.35+/-10.86 muepsilon for the SS in P32 rats. These cyclic forces delivered for 20 min/d over 2 consecutive days induced the expression of MMP-2 gene in the physiologically fused P32 PFS that was not expressed without mechanical stresses. Taken together, these data suggest potentially important roles of MMP genes in the postnatal development of cranial sutures, and their susceptibility to mechanical stresses.

Animals↗
PubMed2005

Stem-cell-driven regeneration of synovial joints.

Mammalian skeletal motion is made possible by synovial joints. Widespread suffering from arthritis and joint injuries has motivated recent effort to regenerate a stem-cell-driven synovial joint condyle implantable in total joint replacement. A single adult stem cell lineage, mesenchymal stem cells, differentiate to form all components of a synovial joint. Whereas localized joint lesions may be repaired by either cell-based or cell-free approaches, regeneration of the entire articular condyle of the synovial joint is unattainable without tissue-forming cells. A series of experiments are presented here to describe our initial attempts to regenerate a synovial joint condyle in the shape and dimensions of a human mandibular condyle, with both cartilaginous and osseous components derived from a single population of rat mesenchymal stem cells. Upcoming challenges are along several intertwining fronts including structural integrity, tissue maturation, mechanical strength and host integration. The synovial joint condyle may turn out to be one of the first 'human body parts' or organs truly regeneratable by stem-cell-derived approaches. Current approaches to regenerate the synovial joint condyle from stem-cell-derived multiple cell lineages may also offer clues for engineering complex organs such as the kidney or liver.

Animals↗
PubMed2005

Tissue-engineered osteochondral constructs in the shape of an articular condyle.

BACKGROUND: An entire articular condyle engineered from stem cells may provide an alternative therapeutic approach to total joint replacement. This study describes our continuing effort to optimize the chondrogenic and osteogenic differentiation from mesenchymal stem cells toward engineering articular condyles in vivo. METHODS: Primary rat bone-marrow mesenchymal stem cells were induced to differentiate into chondrogenic and osteogenic lineages in vitro and were suspended in polyethylene glycol-based hydrogel. The hydrogel cell suspensions, each at a density of 20 x 10(6) cells/mL, were stratified into two separate layers that were molded into the shape and dimensions of an adult human cadaveric mandibular condyle by sequential photopolymerization. The osteochondral constructs fabricated in vitro were implanted in the dorsum of immunodeficient mice for twelve weeks. RESULTS: De novo formation of articular condyles in the shape and dimensions of the adult human mandibular condyle occurred after a twelve-week period of in vivo implantation. Histological evaluation demonstrated two stratified layers of cartilaginous and osseous tissues, and yet there was mutual infiltration of cartilage-like and bone-like tissues into each other's territories. The cartilaginous portion was stained intensively to safranin O and expressed immunolocalized type-II collagen. Chondrocytes adjacent to the tissue-engineered osteochondral junction were enlarged and expressed type-X collagen, typical of hypertrophic chondrocytes. The osseous portion contained bone trabeculae-like structures and expressed immunolocalized type-I collagen, osteopontin, and osteonectin. CONCLUSIONS: A cell encapsulation density of 20 million cells/mL with in vivo incubation for twelve weeks yields further tissue maturation and phenotypic growth of both cartilage-like and bone-like tissues in the tissue-engineered articular condyle.

Animals↗
PubMed2004

Growth and development: hereditary and mechanical modulations.

Growth and development is the net result of environmental modulation of genetic inheritance. Mesenchymal cells differentiate into chondrogenic, osteogenic, and fibrogenic cells: the first 2 are chiefly responsible for endochondral ossification, and the last 2 for sutural growth. Cells are influenced by genes and environmental cues to migrate, proliferate, differentiate, and synthesize extracellular matrix in specific directions and magnitudes, ultimately resulting in macroscopic shapes such as the nose and the chin. Mechanical forces, the most studied environmental cues, readily modulate bone and cartilage growth. Recent experimental evidence demonstrates that cyclic forces evoke greater anabolic responses of not only craniofacial sutures, but also cranial base cartilage. Mechanical forces are transmitted as tissue-borne and cell-borne mechanical strain that in turn regulates gene expression, cell proliferation, differentiation, maturation, and matrix synthesis, the totality of which is growth and development. Thus, hereditary and mechanical modulations of growth and development share a common pathway via genes. Combined approaches using genetics, bioengineering, and quantitative biology are expected to bring new insight into growth and development, and might lead to innovative therapies for craniofacial skeletal dysplasia including malocclusion, dentofacial deformities, and craniofacial anomalies such as cleft palate and craniosynostosis, as well as disorders associated with the temporomandibular joint.

Animals↗
PubMed2004

Heterogeneous nanostructural and nanoelastic properties of pericellular and interterritorial matrices of chondrocytes by atomic force microscopy.

Hyaline cartilage consists of sparse chondrocytes and abundant extracellular matrix. There is a paucity of experimental data in support of the notion of conceivable regional differences in the mechanical properties of chondral matrices. Upon visual differentiation of the pericellular and interterritorial matrices in each of 19 fresh growth plate samples with toluidine blue and alizarin red labels, nanoindentation was applied separately to the pericellular matrix and interterritorial matrix to using fluid-phase atomic force microscopy and real-time imaging. The interterritorial matrix demonstrated elongated parallel ridges, whereas the pericellular matrix showed irregular, short-range elevations with characteristic pores and canals. Analysis of surface contours at 600nm(2) scan size revealed that the interterritorial matrix had significantly greater surface roughness (71+/-18nm; mean+/-SE) than the pericellular matrix (24+/-4nm) ( P< 0.001). The average Young's modulus of the interterritorial matrix was 636+/-123 (kPa), significantly greater than the pericellular matrix (265+/-53kPa) (P< 0.001 ). Thus, the interterritorial matrix appears to possess not only distinct microtopographic contours in comparison with the pericellular matrix, but also significantly greater mechanical stiffness. These distinctive nanostructural and nanomechanical properties may have implications in nutrient diffusion and fluid dynamics, both of which are of vital importance for cartilage health and function.

Animals↗