Cartilage tissue engineering of nasal septal chondrocyte-macroaggregates in human demineralized bone matrix

Tissue Engineering is an important method for generating cartilage tissue with isolated autologous cells and the support of biomaterials. In contrast to various gel-like biomaterials, human demineralized bone matrix (DBM) guarantees some biomechanical stability for an application in biomechanically loaded regions. The present study combined for the first time the method of seeding chondrocyte-macroaggregates in DBM for the purpose of cartilage tissue engineering. After isolating human nasal chondrocytes and creating a three-dimensional macroaggregate arrangement, the DBM was cultivated in vitro with the macroaggregates. The interaction of the cells within the DBM was analyzed with respect to cell differentiation and the inhibitory effects of chondrocyte proliferation. In contrast to chondrocyte-macroaggregates in the cell-DBM constructs, morphologically modified cells expressing type I collagen dominated. The redifferentiation of chondrocytes, characterized by the expression of type II collagen, was only found in low amounts in the cell-DBM constructs. Furthermore, caspase 3, a marker for apoptosis, was detected in the chondrocyte-DBM constructs. In another experimental setting, the vitality of chondrocytes as related to culture time and the amount of DBM was analyzed with the BrdU assay. Higher amounts of DBM tended to result in significantly higher proliferation rates of the cells within the first 48 h. After 96 h, the vitality decreased in a dose-dependent fashion. In conclusion, this study provides the proof of concept of chondrocyte-macroaggregates with DBM as an interesting method for the tissue engineering of cartilage. The as-yet insufficient redifferentiation of the chondrocytes and the sporadic initiation of apoptosis will require further investigations.     

The properties of bioengineered chondrocyte sheets for cartilage regeneration

Background  

Although the clinical results of autologous chondrocyte implantation for articular cartilage defects have recently improved as a result of advanced techniques based on tissue engineering procedures, problems with cell handling and scaffold imperfections remain to be solved. A new cell-sheet technique has been developed, and is potentially able to overcome these obstacles. Chondrocyte sheets applicable to cartilage regeneration can be prepared with this cell-sheet technique using temperature-responsive culture dishes. However, for clinical application, it is necessary to evaluate the characteristics of the cells in these sheets and to identify their similarities to naive cartilage.     

Fluid-induced low shear stress improves cartilage like tissue fabrication by encapsulating chondrocytes

In the recent years, there has been considerable development in the regenerative medicine, which aims to repair, regenerate, and improve injured articular cartilage. The aim of the present study was to investigate the effect of flow-induced shear stress in perfusion bioreactor on alginate encapsulating chondrocytes. The shear stress imposed on the cells in the culture chamber of bioreactor was predicted with computational fluid dynamic. Bovine nasal chondrocytes were isolated and expanded to obtain a pellet. The cell pellet was resuspends in alginate solution, transferred to the culture chamber, and dynamically cultured under direct perfusion. At the end of culture, tissue constructs were examined histologically and by immunohistochemistry. The results of computational fluid dynamic modeling revealed that maximum wall shear stress was 4.820 × 10^?3 Pascal. Macroscopic views of the alginate/chondrocyte beads suggested that it possessed constant shape but were flexible. Under inverted microscope, round shape of chondrocyte observed. Cell distribution was homogeneous throughout the scaffold. Tissue construct subjected to shear showed morphological features, which are characteristic for natural cartilage. Immunohistochemistry results revealed immunopositivity for type II collagens in tissue constructs samples. Flow induced shear stress in the perfusion bioreactor and chnondrocyte encapsulation provide environment to support cell growth, and tissue regeneration and improve cartilage like tissue fabrication.     

84 例基于三脚架结构改建的鼻尖综合整形术的临床总结

目的:总结基于鼻翼软骨三脚架结构的改建技术在鼻尖综合整形术中的应用经验。方法:从2012年09月到2015年02月间,共84例求美者在我院进行初次鼻尖综合整形术。3例为男性,81例为女性。年龄20-45岁,平均年龄31.7岁。其中鼻头肥大伴鼻背低平65例,行鼻翼软骨缝合+鼻翼软骨切除+鼻假体+自体软骨帽状移植术;鼻头肥大、鼻背低平伴鼻小柱短小19例,行自体软骨鼻小柱支撑+鼻翼软骨切除+鼻翼软骨缝合+鼻假体植入+自体软骨帽状移植术。结果:84例求美者术后随访1个月-2年,除1例病例鼻头过于肥大,鼻尖形态改善不明显以外,其余求美者鼻额角及鼻尖角度及均较术前有明显改善,鼻小柱短小组的鼻小柱长度也较术前有明显改善。所有病例切口瘢痕均不明显,无明显并发症出现。结论:针对不同鼻翼软骨发育条件下的病人,个性化的应用鼻翼软骨三脚架结构改建的鼻尖综合整形术具有较好的临床效果,须根据不同病人特点选用。     

Anatomic reconstruction of the nasal tip cartilages in secondary and reconstructive rhinoplasty

Most techniques for secondary rhinoplasty assume that useful residual remnants of the tip cartilages remain, but frequently the alar cartilages are missing--unilaterally, bilaterally, completely, or incompletely--with loss of the lateral crura, middle crura, and parts of the medial crura. In such severe cases, excision of scar tissue and the residual alar remnants and their replacement with nonanatomic tip grafts have been recommended. Multiple solid, bruised, or crushed cartilage fragments are positioned in a closed pocket or solid shield-shaped grafts are fixed with sutures during an open rhinoplasty. These onlay filler grafts only increase tip projection and definition. Associated tip abnormalities (alar rim notching, columellar retraction, nostril distortion) are not addressed. Problems with graft visibility, an unnatural appearance, or malposition have been noted. Fortunately, techniques useful in reconstructive rhinoplasty can be applied to severe cosmetic secondary deformities. Anatomic cartilage replacements similar in shape, bulk, and position to normal alar cartilages can be fashioned from septal, ear, and rib cartilage, fixed to the residual medial crura and/or a columellar strut, and bent backward to restore the normal skeletal framework of the tip. During an open rhinoplasty, a fabricated and rigid framework is designed to replace the missing medial, middle, or lateral crus of one or both alar cartilages. The entire alar tripod is recreated. These anatomic alar cartilage reconstructive grafts create tip definition and projection, fill the lobule and restore the expected lateral convexity, position the columella and establish columellar length, secure and position the alar rim, and brace the external valve against collapse, support the vestibular lining, and restore a nostril shape. The anatomic form and function of the nasal tip is restored. This technique is recommended when alar cartilages are significantly destroyed or absent in secondary or reconstructive rhinoplasty and the alar remnants are insufficient for repair. Anatomically designed alar cartilage replacements allow an aesthetically structured skeleton to contour the overlying skin envelope. Problems with displacement are minimized by graft fixation. Graft visibility is used to the surgeon's advantage. A rigidly supported framework with a nasal shape can mold a covering forehead flap or the scarred tip skin of a secondary rhinoplasty and create a result that may approach normal. Anatomic alar cartilage reconstructions were used in eight reconstructive and eight secondary rhinoplasties in the last 5 years. Their use in the repair of postrhinoplasty deformities is emphasized.     

Resorbable internal splint: an adjunct to primary correction of unilateral cleft lip-nasal deformity

There is usually some relapse in position of the alar cartilage after primary repair of unilateral cleft lip. Therefore, preoperative or postoperative external splinting has been recommended to supplement either closed or open suspension of the alar cartilage. The authors present a method using a resorbable internal nostril splint to shield the positioned alar cartilage from deformational forces caused by scar, and thus avoiding the problems associated with external splinting. An internal nasal splint was placed in 15 infants during repair of unilateral complete cleft lip and nasal deformity. The nasal morphology was compared with that of 15 control patients who had the same nasolabial procedure without internal splinting. Average follow-up time was 20.4 months (range, 4 to 30 months). Photogrammetric analysis showed that asymmetry of the alar contours averaged 8.6 percent in the splinted patients, as compared with 23 percent for controls (p <0.01). Thus, alar asymmetry was decreased two-thirds in the splinted group. An internal resorbable nasal splint is an adjunct to open alar suspension in primary repair of the unilateral cleft lip nasal deformity. An internal nasal splint protects the corrected alar cartilage longer than an external splint and eliminates drawbacks, such as necrosis, cutaneous depression of the nostril sill, and patient noncompliance. This strategy of temporary internal support of healing cartilage has other applications.     

Anatomy of the Caucasian alar groove

Anatomic studies performed on the noses of 15 cadavers examined the alar groove, alar lobule, and lower lateral crus areas both microscopically and on gross appearance to determine what effect these structures have on overall nasal appearance. In contrast to the findings of previous studies, the authors found the alar lobule to be an area in which dermis is interdigitated with muscle throughout and up to the alar rim. The anteroposterior lengths of the lower lateral crura were again seen to vary in length, presence or absence of accessory cartilages, and shape. Neither corrugation of the posterior elongation nor overlap of the accessory cartilages of the lower lateral cartilage had an effect on phenotype; sharp angles formed by the cartilage were blunted by the layer of fibrofatty muscular tissue between the cartilage and the skin. The alar groove, which lies at the junction of the lower lateral crus (medially) and the alar lobule (laterally), is defined not as much by a muscular attachment between the perichondrium of the lower lateral cartilage and the vestibular mucosa as by a bulging in the fatty layer on one side of the groove (within the cheek, lateral nasal wall, and nasal tip) and a relative paucity of fatty tissue on its other side (within the alar lobule).     

The Mechanical Behaviour of Chondrocytes Predicted with a Micro-structural Model of Articular Cartilage

The integrity of articular cartilage depends on the proper functioning and mechanical stimulation of chondrocytes, the cells that synthesize extracellular matrix and maintain tissue health. The biosynthetic activity of chondrocytes is influenced by genetic factors, environmental influences, extracellular matrix composition, and mechanical factors. The mechanical environment of chondrocytes is believed to be an important determinant for joint health, and chondrocyte deformation in response to mechanical loading is speculated to be an important regulator of metabolic activity. In previous studies of chondrocyte deformation, articular cartilage was described as a biphasic material consisting of a homogeneous, isotropic, linearly elastic solid phase, and an inviscid fluid phase. However, articular cartilage is known to be anisotropic and inhomogeneous across its depth. Therefore, isotropic and homogeneous models cannot make appropriate predictions for tissue and cell stresses and strains. Here, we modelled articular cartilage as a transversely isotropic, inhomogeneous (TI) material in which the anisotropy and inhomogeneity arose naturally from the microstructure of the depth-dependent collagen fibril orientation and volumetric fraction, as well as the chondrocyte shape and volumetric fraction. The purpose of this study was to analyse the deformation behaviour of chondrocytes using the TI model of articular cartilage. In order to evaluate our model against experimental results, we simulated indentation and unconfined compression tests for nominal compressions of 15%. Chondrocyte deformations were analysed as a function of location within the tissue. The TI model predicted a non-uniform behaviour across tissue depth: in indentation testing, cell height decreased by 43% in the superficial zone and between 11 and 29% in the deep zone. In unconfined compression testing, cell height decreased by 32% in the superficial zone, 25% in the middle, and 18% in the deep zones. This predicted non-uniformity is in agreement with experimental studies. The novelty of this study is the use of a cartilage material model accounting for the intrinsic inhomogeneity and anisotropy of cartilage caused by its microstructure.     

A problem-oriented and segmental open approach to alar cartilage losses and alar length discrepancies

Alar cartilage losses and alar length discrepancies present problems in nasal tip support, contour, and symmetry. The true extent of the cartilage defect is often not apparent until the time of surgery. This article examines a problem-oriented and segmental open approach to such deformities. It is based on the size of the defect, its location within the dome and lateral crus, and the presence or absence of alar collapse. The defects are classified as major when there is a total or near total loss of the lateral crus, moderate when more than 5 mm is involved, and minor when less than 5 mm is affected. In major defects, a segmental reconstruction of the nasal tip cartilages is undertaken. It consists of a septal graft for columellar support and a conchal shield graft and umbrella graft for nasal tip contour. The whole length of the lateral crus is not reconstructed unless alar collapse is present. In moderate cartilage defects, usually seen laterally in secondary rhinoplasties, the remaining central dome segments are remodeled with shaping sutures. Moderate cartilage length discrepancies, as seen in unilateral cleft lip noses, are equalized through reversed alar rotations. The short crus is rotated laterally, taking length from the medial crus, and the long crus is rotated medially, with the excess advanced into the medial crural footplate. Additional shortening of the long crus can be achieved through cartilage division and advancement. The balanced alar units are then raised with tip projection-vector sutures, and onlay grafts are added if required. In minor cartilage losses, symmetry is usually obtained by shortening the opposite uninjured crus. A total of 33 patients are examined in this review. The average follow-up is 14 months. An improvement in nasal tip shape and support was achieved in all patients.     

Injurious mechanical compression of bovine articular cartilage induces chondrocyte apoptosis

A bovine cartilage explant system was used to evaluate the effects of injurious compression on chondrocyte apoptosis and matrix biochemical and biomechanical properties within intact cartilage. Disks of newborn bovine articular cartilage were compressed in vitro to various peak stress levels and chondrocyte apoptotic cell death, tissue biomechanical properties, tissue swelling, glycosaminoglycan loss, and nitrite levels were quantified. Chondrocyte apoptosis occurred at peak stresses as low as 4.5 MPa and increased with peak stress in a dose-dependent manner. This increase in apoptosis was maximal by 24 h after the termination of the loading protocol. At high peak stresses (>20 MPa), greater than 50% of cells apoptosed. When measured in uniaxial confined compression, the equilibrium and dynamic stiffness of explants decreased with the severity of injurious load, although this trend was not significant until 24-MPa peak stress. In contrast, the equilibrium and dynamic stiffness measured in radially unconfined compression decreased significantly after injurious stresses of 12 and 7 MPa, respectively. Together, these results suggested that injurious compression caused a degradation of the collagen fibril network in the 7- to 12-MPa range. Consistent with this hypothesis, injurious compression caused a dose-dependent increase in tissue swelling, significant by 13-MPa peak stress. Glycosaminoglycans were also released from the cartilage in a dose-dependent manner, significant by 6- to 13-MPa peak stress. Nitrite levels were significantly increased above controls at 20-MPa peak stress. Together, these data suggest that injurious compression can stimulate cell death as well as a range of biomechanical and biochemical alterations to the matrix and, possibly, chondrocyte nitric oxide expression. Interestingly, chondrocyte programmed cell death appears to take place at stresses lower than those required to stimulate cartilage matrix degradation and biomechanical changes. While chondrocyte apoptosis may therefore be one of the earliest responses to tissue injury, it is currently unclear whether this initial cellular response subsequently drives cartilage matrix degradation and changes in the biomechanical properties of the tissue.     

Biodegradable zinc oxide composite scaffolds promote osteochondral differentiation of mesenchymal stem cells

Osteoarthritis (OA) involves the degeneration of articular cartilage and subchondral bone. The capacity of articular cartilage to repair and regenerate is limited. A biodegradable, fibrous scaffold containing zinc oxide (ZnO) was fabricated and evaluated for osteochondral tissue engineering applications. ZnO has shown promise for a variety of biomedical applications but has had limited use in tissue engineering. Composite scaffolds consisted of ZnO nanoparticles embedded in slow degrading, polycaprolactone to allow for dissolution of zinc ions over time. Zinc has well-known insulin-mimetic properties and can be beneficial for cartilage and bone regeneration. Fibrous ZnO composite scaffolds, having varying concentrations of 1–10 wt.% ZnO, were fabricated using the electrospinning technique and evaluated for human mesenchymal stem cell (MSC) differentiation along chondrocyte and osteoblast lineages. Slow release of the zinc was observed for all ZnO composite scaffolds. MSC chondrogenic differentiation was promoted on low percentage ZnO composite scaffolds as indicated by the highest collagen type II production and expression of cartilage-specific genes, while osteogenic differentiation was promoted on high percentage ZnO composite scaffolds as indicated by the highest alkaline phosphatase activity, collagen production, and expression of bone-specific genes. This study demonstrates the feasibility of ZnO-containing composites as a potential scaffold for osteochondral tissue engineering.     

Synergistic action of fibroblast growth factor-2 and transforming growth factor-beta1 enhances bioprinted human neocartilage formation

Bioprinting as a promising but unexplored approach for cartilage tissue engineering has the advantages of high throughput, digital control, and highly accurate placement of cells and biomaterial scaffold to the targeted 3D locations with simultaneous polymerization. This study tested feasibility of using bioprinting for cartilage engineering and examined the influence of cell density, growth, and differentiation factors. Human articular chondrocytes were printed at various densities, stimulated transiently with growth factors and subsequently with chondrogenic factors. Samples were cultured for up to 4 weeks to evaluate cell proliferation and viability, mechanical properties, mass swelling ratio, water content, gene expression, ECM production, DNA content, and histology. Bioprinted samples treated with FGF-2/TGF-β1 had the best chondrogenic properties among all groups apparently due to synergistic stimulation of cell proliferation and chondrogenic phenotype. ECM production per chondrocyte in low cell density was much higher than that in high cell seeding density. This finding was also verified by mechanical testing and histology. In conclusion, cell seeding density that is feasible for bioprinting also appears optimal for human neocartilage formation when combined with appropriate growth and differentiation factors.     

Emergence of chondrogenic progenitor stem cells in transplantation biology-prospects and drawbacks

Avascular tissues such as a cartilage contains a unique type of cell called as the chondrocyte. We, however, have not understood the origin of the chondrocyte population and how this population is maintained in the normal tissue. In spite of being considered to be a simple tissue, scientist had always faced difficulties to engineer this tissue. This is because different structural regions of the articular cartilage were never understood. In addition to this, the limited self-repair potential of cartilage tissue and lack of effective therapeutic options for the treatment of damaged cartilage has remained an unsolved problem. Mesenchymal stem cell based therapy may provide a solution for cartilage regeneration. This is due to their ability to differentiate into chondrogenic lineage when appropriate conditions are provided. An ideal cell source, a three-dimensional cell culture, a suitable scaffold material that accomplishes all the necessary properties and bioactive factors in specific amounts are required to induce chondrocyte differentiation and proliferation. Cartilage tissue engineering is a promising and rapidly expanding area of research that assures cartilage regeneration. However, many unsolved questions concerning the mechanism of engraftment of chondrocytes following transplantation in vivo, biological safety after transplantation and the retention of these cells for lifetime remain to be addressed that is possible only through years of extensive research. Further studies are therefore required to estimate the long-term sustainability of these cells in the native tissue, to identify well suited delivery materials and to have a thorough understanding of the mechanism of interaction between the chondrocytes and extracellular matrix and time is not far when this cell based therapy will provide a comprehensive cure to cartilage disease.     

A novel rotating-shaft bioreactor for two-phase cultivation of tissue-engineered cartilage

A novel rotating-shaft bioreactor (RSB) was developed for two-phase cultivation of tissue-engineered cartilage. The reactor consisted of a rotating shaft on which the chondrocyte/scaffold constructs (7.5 mm diameter x 3.5 mm thickness) were fixed and a reactor vessel half-filled with medium. The horizontal rotation of the shaft resulted in alternating exposure of the constructs to gas and liquid phases, thus leading to efficient oxygen and nutrient transfer, as well as periodically changing, mild shear stress exerting on the construct surfaces (0-0.32 dyn/cm2 at 10 rpm), as revealed by computer simulation. Strategic operation of the RSB (maintaining rotating speed at 10 rpm for 3 weeks and lowering the speed to 2 rpm in week 4) in combination with higher seeding density (6 x 10(6) chondrocytes/scaffold) and medium perfusion resulted in uniform cell distribution and increased glycosaminoglycan (3.1 mg/scaffold) and collagen (7.0 mg/scaffold) deposition. The 4-week constructs resembled native cartilages in terms of not only gross appearance and cell morphology but also distributions of glycosaminoglycan, total collagen, and type II collagen, confirming the maintenance of chondrocyte phenotype and formation of cartilage-like constructs in the RSB cultures. In summary, the novel RSB may be implicated for in vitro study of chondrogenesis and de novo cartilage development under periodic mechanical loading. With proper optimization of the culture conditions, a RSB may be employed for the production of cartilage-like constructs.     

A radical method of correcting the nasal deformity in adult patients with repaired unilateral lip clefts

A method of rhinoseptoplasty is described, which combines principles of several well-known procedures, with innovations introduced by the author, for the purpose of eliminating the causes of complex distortions of the lip, maxilla, and nose in unilateral clefts. This method aims at creating a secure support for the atrophic alar cartilage with a pedicled cartilage flap taken from the normal alar cartilage. Elevation of the dome and elongation of the columella on the cleft side are achieved by interdigitating mucocutaneous flaps. To improve symmetry and relieve nasal obstruction, the ala on the normal side is also corrected, as well as the deflected septal cartilage and the anterosuperior margin of the vomer.     

Phenotypic analysis of bovine chondrocytes cultured in 3D collagen sponges: effect of serum substitutes

Repair of damaged cartilage usually requires replacement tissue or substitute material. Tissue engineering is a promising means to produce replacement cartilage from autologous or allogeneic cell sources. Scaffolds provide a three-dimensional (3D) structure that is essential for chondrocyte function and synthesis of cartilage-specific matrix proteins (collagen type II, aggrecan) and sulfated proteoglycans. In this study, we assessed porous, 3D collagen sponges for in vitro engineering of cartilage in both standard and serum-free culture conditions. Bovine articular chondrocytes (bACs) cultured in 3D sponges accumulated and maintained cartilage matrix over 4 weeks, as assessed by quantitative measures of matrix content, synthesis, and gene expression. Chondrogenesis by bACs cultured with Nutridoma as a serum replacement was equivalent or better than control cultures in serum. In contrast, chondrogenesis in insulin-transferrin-selenium (ITS⁺³) serum replacement cultures was poor, apparently due to decreased cell survival. These data indicate that porous 3D collagen sponges maintain chondrocyte viability, shape, and synthetic activity by providing an environment favorable for high-density chondrogenesis. With quantitative assays for cartilage-specific gene expression and biochemical measures of chondrogenesis in these studies, we conclude that the collagen sponges have potential as a scaffold for cartilage tissue engineering.     

Bilateral cleft lip reconstruction

Over a period of 8 years 140 bilateral cleft lips were operated using a muscle-repositioning banked fork-flap cheiloplasty. The use of buccal mucosal flaps in the intercartilaginous incision is helpful to decrease scarring and contracture by facilitating alar cartilage repositioning and wound closure without tension. Adding mucosa from the inferior turbinate makes complete wound closure relatively easy without tension. A lateral lip orbicularis muscle flap with white skin roll and vermilion is recommended for reconstruction of the Cupid's bow. Muscle continuity by freeing the muscle in one sheet and repositioning in front of the premaxilla with creation of a buccal alveolar sulcus is stressed to prevent the necessity of reentering the lip in a second procedure. The elongation of the columella is done at 1 to 6 years of age by advancing nasal floor tissue onto the columella and repositioning the alar cartilages superiorly and medially. When nasal floor tissue is inadequate, columellar lengthening is done by the use of a composite free ear graft.     

A cell leakproof PLGA‐collagen hybrid scaffold for cartilage tissue engineering

A cell leakproof porous poly(DL ‐lactic‐co‐glycolic acid) (PLGA)‐collagen hybrid scaffold was prepared by wrapping the surfaces of a collagen sponge except the top surface for cell seeding with a bi‐layered PLGA mesh. The PLGA‐collagen hybrid scaffold had a structure consisting of a central collagen sponge formed inside a bi‐layered PLGA mesh cup. The hybrid scaffold showed high mechanical strength. The cell seeding efficiency was 90.0% when human mesenchymal stem cells (MSCs) were seeded in the hybrid scaffold. The central collagen sponge provided enough space for cell loading and supported cell adhesion, while the bi‐layered PLGA mesh cup protected against cell leakage and provided high mechanical strength for the collagen sponge to maintain its shape during cell culture. The MSCs in the hybrid scaffolds showed round cell morphology after 4 weeks culture in chondrogenic induction medium. Immunostaining demonstrated that type II collagen and cartilaginous proteoglycan were detected in the extracellular matrices. Gene expression analyses by real‐time PCR showed that the genes encoding type II collagen, aggrecan, and SOX9 were upregulated. These results indicated that the MSCs differentiated and formed cartilage‐like tissue when being cultured in the cell leakproof PLGA‐collagen hybrid scaffold. The cell leakproof PLGA‐collagen hybrid scaffolds should be useful for applications in cartilage tissue engineering. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010     

Chondrocyte hypertrophy in skeletal development,growth, and disease

Most of our bones form through the process of endochondral ossification, which is tightly regulated by the activity of the cartilage growth plate. Chondrocyte maturation through the various stages of growth plate physiology ultimately results in hypertrophy. Chondrocyte hypertrophy is an essential contributor to longitudinal bone growth, but recent data suggest that these cells also play fundamental roles in signaling to other skeletal cells, thus coordinating endochondral ossification. On the other hand, ectopic hypertrophy of articular chondrocytes has been implicated in the pathogenesis of osteoarthritis. Thus, a better understanding of the processes that control chondrocyte hypertrophy in the growth plate as well as in articular cartilage is required for improved management of both skeletal growth disorders and osteoarthritis. This review summarizes recent findings on the regulation of hypertrophic chondrocyte differentiation, the cellular mechanisms involved in hypertrophy, and the role of chondrocyte hypertrophy in skeletal physiology and pathophysiology. Birth Defects Research (Part C) 102:74–82, 2014. © 2014 Wiley Periodicals, Inc.     

Cleft lip nose correction with onlay calvarial bone graft and suture suspension in Oriental patients

To correct the secondary cleft lip nose deformity in Oriental patients, many alar cartilage mobilization and suspension techniques have been developed. However, these techniques have critical limitations. One of the limitations is the suspension vector, and another is suspension power. The suspension vector is from inferior to superior and from the deformed alar cartilage to the normal alar cartilage. Thus, the vector is not suitable for normal nasal tip projection. The suspension power is not satisfactory because Oriental people have underdeveloped, thin alar cartilages and thick skin. So, the suspended, deformed alar cartilage may relapse and pull the normal alar cartilage to the deformed side. To overcome these limitations, the authors use the cantilever calvarial bone graft for tip projection; it also serves as a strong, rigid framework for cartilage and soft-tissue suspension. Using these techniques, the authors can create normal nasal tip projection and a normal looking nasal aperture.