Bony Nodules Research Articles

Clinical Characteristics and Outcomes in Tracheobronchopathia Osteochondroplastica: A Scoping Review

Background and Objective: Tracheobronchopathia osteochondroplastica (TBOCP) is a rare, benign condition characterised by the presence of multiple bony and cartilaginous nodules in the tracheal and bronchial submucosa. Its etiology remains unknown, and clinical presentations and management vary. Methods: We conducted a scoping review to evaluate clinical and radiological characteristics, diagnostic investigations and prognostic outcomes of TBOCP in adults by exploring Pubmed and SCOPUS databases. Results: From the search results of 675 studies, 98 were included in this scoping review. TBOCP has a myriad of presenting symptoms and clinical severity but is notably an asthma mimic, displaying an obstructive pattern on spirometry. Bronchoscopic tools were the most common interventional diagnostic or management tool. Conclusion: While the etiology of TBOCP remains unknown, clinicians are alerted to its varied presentations and classical histopathological and gross morphological appearance.

A case report of tracheobronchopathia osteochondroplastica

Background: Tracheobronchopathia Osteochondroplastica (TO) is a benign disease of low incidence that is characterized by multiple submucosal cartilaginous and bony tracheobronchial nodules

Clinical course of tracheobronchopathia osteochondroplastica.

BackgroundTracheobronchopathia osteochondroplastica (TPO) is characterized by the presence of diffuse cartilaginous or bony submucosal nodules that lead to airway lumen narrowing. So far, there was no study in South Korea analysing a large number of TPO patients. We aimed to elucidate its treatment strategy and clinical course by analysing the characteristics of TPO patients.MethodsIn this retrospective study, we reviewed the clinical data of 40 patients diagnosed with TPO by bronchoscopy between October 1997 and April 2019 at a single referral hospital.ResultsOf the 40 patients, 26 (65.0%) were male and the median age was 63.0 years. The most common symptom was cough (n=12, 30%). Pulmonary function test (PFT) revealed an obstructive pattern in 10 (25.7%) patients. Chest computed tomography (CT) scan showed 23 (62.6%) patients with diffuse narrowing and calcified nodules. In bronchoscopy, the entire trachea was found to be involved in 30 (75.0%) patients and airway narrowing was identified in 6 (15.0%) patients. Endobronchial biopsies were obtained from 15 patients and the most common findings included typical cartilaginous and bony tissues (n=14, 93.3%). Since most patients were asymptomatic or had mild symptoms, they did not undergo any specific treatment. Of the 19 symptomatic patients, 2 (5.0%) patients received laser therapy for treating tracheal stenosis.ConclusionsTPO is a slowly progressing disease and is well managed with conservative therapies. Although TPO shows a distinctive pattern by bronchoscopy, it follows a benign clinical course.

Rare Manifestation of Idiopathic Tracheobronchopathia Osteochondroplastica: Misdiagnosed and Untreated Entity?

Tracheobronchopathia osteochondroplastica (TBPO) is a rare benign disease of unknown cause, in which multiple cartilaginous or bony submucosal nodules project into the trachea and proximal bronchi. It usually occurs in men in their fifth decade and can cause airway obstruction, bleeding and chronic cough; patients are more prone to post-obstructive pneumonia and chronic lung infection in some instances. We report a case of a 69-year-old female who presented with shortness of breath and lower extremity swelling over the past couple of weeks. Echocardiography (ECHO) was consistent with heart failure with preserved ejection fraction, and she was treated with diuretics accordingly. Imaging revealed persistent pleural effusions bilaterally, more pronounced on the right side. During the course of her hospitalization, the patient coded once and had to be resuscitated. She had bronchoscopy done and pathology was consistent with TBPO. In this condition, there are numerous osseous or cartilaginous submucosal nodules in the trachea and the main bronchus and nodules are formed due to the deposition of calcium phosphate that results in the proliferation of osseous and cartilaginous structures resulting in the obstruction of large airways. Treatment for the most part is supportive and resolves around bronchodilators for symptomatic relief.

Tracheobronchopathia osteochondroplastica in a patient requiring extracorporeal membrane oxygenation: a case report

Tracheobronchopathia osteochondroplastica (TO) is a large airway disorder, characterised by bony nodule growth on the anterior and lateral walls of the trachea and bronchi. Its diagnosis is based on the ‘rock garden’ appearance on bronchoscopy.[1–3][1] However, as an uncommon condition with

Adhesion, proliferation and osteogenic differentiation of mesenchymal stem cells in 3D printed poly-ε-caprolactone/hydroxyapatite scaffolds combined with bone marrow clots.

Mesenchymal stem cells (MSCs), a stem cell population capable of multi-lineage differentiation, bound to porous biomaterial scaffolds, are widely used for bone tissue regeneration. However, there is evidence to suggest that MSC collection from bone marrow and expansion in vitro may result in phenotypic changes including a loss of differentiation potential and cell senescence. The aim of the present study was to find a facile and efficient approach to enable MSC adhesion and proliferation to scaffolds with osteogenic differentiation. Unprocessed bone marrow blood from the condyle of the distal femur in the rabbits were added to three-dimensional (3D) printed porous poly-ε-caprolactone/hydroxyapatite (PCL/HA) scaffolds with bone marrow clots (MC) formed, using two different methods for Group A (MC enriched scaffolds) and Group B (MC combined scaffolds), and then were cultured in osteogenic medium for 4 weeks. The scaffolds were assessed macroscopically and microscopically. Scaffold bioactivity and the proliferation and osteogenic differentiation of seeded MSCs were measured. Higher cellular viability and greater cell numbers in the scaffolds at later phases of culture were observed in Group B compared with Group A. In addition, Group B was associated with greater osteoinductivity, alkaline phosphatase activity and bony nodule formation, as assessed using scanning electron microscopy. Furthermore, reverse transcription-quantitative polymerase chain reaction analysis revealed that more osteogenic differentiation was present in Group B, compared with Group A. MC combined scaffolds proved to be a highly efficient, reliable and simple novel method for MSC adhesion, proliferation and differentiation. The MC combined PCL-HA multi-scale porosity scaffold may represent a candidate for future bone regeneration studies.

Erupted Large Anterior Maxillary Complex Odontoma: A Rare Dental Hamartoma.

A 13-year-old male patient reported with the complaint of pain and swelling in left upper region. His medical history was non-significant and this was his first visit to the dentist. Extra-orally there was no asymmetry or palpable lymph nodes. Intraoral examination revealed absence of left maxillary canine. On inspection, swelling was noticed on labial side of unerupted tooth. A well defined firm bony nodule measuring approximately 10cm fixed to the underlying tissue and not mobile when palpated [Table/Fig-1]. There was absence of buccal and lingual cortical plates in the same region.

Congenital complex corneal choristoma associated with unilateral bony calvarial defects, subcutaneous nodules, and alopecia

Complex corneal choristoma is a rare finding and its relationship with systemic disease is poorly understood. We present a 3-day-old boy with the constellation of left-sided congenital complex corneal choristoma, limbal dermoid, ipsilateral bony skull defects, and bilateral subcutaneous vascularized nodules with overlying alopecia and scalp nevi. To our knowledge this is the first case of complex choristoma involving the presence of associated bony calvarial defects. This presentation may contribute to a greater understanding of the systemic findings associated with the condition. Furthermore, it may shed light on the possible syndromic spectrum associated with complex choristoma and its underlying pathophysiology.

Acquired Perforating Osteoma Cutis.

Dear Editor: Osteoma cutis is a rare, benign condition characterized by dermal or subcutaneous bone formation1 that presents as stony hard nodules2. Although the mechanism of bone formation remains unclear, it is speculated that resident fibroblasts or nests of pleuripotent mesenchymal cells differentiate into osteoblasts to form bone tissue2. This disease can be divided into two types according to origin. The primary type, which accounts for 15% of cases, occurs in the absence of predisposing factors. The secondary type, also known as the acquired type, occurs in cases involving preexisting inflammatory or neoplastic disease, or trauma2. Herein, we report a case of acquired perforating osteoma cutis probably due to chronic irritation. A 40-year-old woman with diabetes mellitus had a solitary 1×0.5-cm erythematous nodule and central keratotic crater on her left breast for 20 years (Fig. 1). She reported that the lesion thickened and oozed fluid for 2 years. Laboratory test results for thyroid and parathyroid hormone were within normal limits. Mammography revealed solitary calcification at the same site, which was interpreted as a phlebolith. Excisional biopsy was performed for diagnosis and removal. The specimen had a central keratotic plug comprising osseous tissue with surrounding inflammatory cells (Fig. 2A) and bony nodules perforating the overlying epidermis (Fig. 2B). Von Kossa staining showed calcium deposition (Fig. 2C). On the basis of these findings, we diagnosed the patient with acquired perforating osteoma cutis. Fig. 1 A solitary, oozing, 1×0.5-cm erythematous papule and central keratotic crater on left the breast. Fig. 2 (A) A central well-demarcated keratotic plug in the epidermis, granulomatous inflammation and fibrosis in the dermis (H&E, ×40). Inset: the calcified plug was composed of osteoblasts, osteoclasts, and osteocytes (H&E, ×400). ... Perforation commonly occurs in perforating collagenosis, perforating folliculitis, granuloma annulare, and calcinosis cutis1. Perforating osteoma cutis is a very rare condition; few cases have been reported1,3,4. Several potential mechanisms of perforation have been described: (a) transepidermal elimination, which is a dermal-induced epidermal reaction to eliminate foreign bodies, degenerated connective tissue or keratin, calcium deposits, and/or ectopic tissue5; (b) the pressure effect from underlying tissue1; (c) simple upward growth of underlying tissue; and (d) superficial inflammation caused by external trauma, leading to the degeneration and perforation of the epidermis5. We speculate persistent irritation by brassieres might have induced superficial inflammation and stimulated the differentiation of cells into osteoblasts in the present case. Calcification occurred much later, and calcium-containing ectopic bone tissue induced transepidermal elimination. In addition, the pressure effect and simple upward growth of bony nodules might have facilitated epidermal perforation. In the present case, the presence of clustered osseous tissue with surrounding dermal inflammatory cells supports the idea that the lesion was secondary to trauma3. Furthermore, von Kossa staining revealed calcium deposition, which indicates the chronic phase of ossification. Osteoma cutis is rare condition often misdiagnosed as thrombophlebitis on radiography. In the present case, a radiologist interpreted the calcification observed on mammography as a phlebolith. The accurate diagnosis of osteoma cutis requires histopathologic confirmation or bone scan. Surgical removal is commonly performed to treat osteoma cutis2. Our patient was successfully treated with excision, and no recurrence has been noted during 6 months of follow-up. In summary, we report a case of secondary perforating osteoma cutis probably due to chronic irritation. Histopathologic confirmation of bone tissue or bone scan is required to establish a definite diagnosis of osteoma cutis.

Orbital Osteoma

This study reviews the clinical presentation and management of 11 cases of sino-orbital osteoma. The medical records of patients with primary (originating from orbital bone) and secondary (originating from the paranasal sinuses) orbital osteoma from the academic practices of 4 surgeons (A.V.C., M.J.L., P.J.D., V.D.D.) were reviewed for clinical presentation and course, pathologic study, and radiologic reports. A Medline search of English-language literature on orbital osteomas was conducted for comparison with these findings. Eleven cases of primary (1) and secondary (10) orbital osteoma were reviewed, with a mean follow up of 16 months. Seven patients were women. Ages ranged from 15-68 years, with a median of 40 years. Presenting complaints included slowly progressive globe displacement, palpable bony nodule, pain, and diplopia. Surgery was performed in 10 cases. Surgical approach varied according to location and size of each lesion and was performed in combination with otolaryngology and neurosurgery services as needed. Reconstruction included sculpting osteomatous bone to natural orbital contours, repair of orbital wall defects with implants, and obliteration of frontal sinus. Lesions demonstrated mixed compact, cancellous, and fibrous histologic subtypes. Osteomas are the most common tumor of the paranasal sinuses (noted in up to 3% of coronal CT images), but secondary extension in or primary involvement of the orbit is rare. A variety of surgical approaches led to successful outcomes in this series. Complete surgical removal is not always necessary, and partial sculpting may relieve symptoms and cause less surgical morbidity in selected cases.

Tracheobronchopathia osteochondroplastica: a case report and literature review.

Tracheobronchopathia osteochondroplastica (TO) was diagnosed in a 52-year-old male with prolonged dry cough. Computerized tomography (CT) demonstrated that there were multiple calcified nodules in the anterolateral wall of trachea, sparing the posterior tracheal membrane. Fiberoptic bronchoscopy (FOB) showed that submucosal nodules protruded into the airway lumen. Histopathological exam found ossification and cartilage in the submucosa. TO is a scarce benign disorder, characterized by submucosal bony and cartilaginous nodules. The clinical manifestation is undistinguished and treatment is symptomatically dependent. FOB is a definitive diagnostic procedure. The characteristics of FOB finding are described as beaded, spiculate, rock garden, or cobble-stoned like nodules, which projected into the tracheobronchus lumen, sparing the posterior wall. Histopathological exam might re-confirm the diagnosis, finding ossification and cartilage in the submucosa of airway. Awareness of TO is significantly important, especially in chronic cough patients with special CT image, and FOB should be performed to confirm the diagnosis.

Case report of tracheobronchopathia osteochondroplastica

Introduction: Tracheobronchopathia osteochondroplastica (TPO) is a rare entity characterized by bony and cartilaginous submucosal nodules which project into the tracheal–bronchial lumen. Nodules sometimes reach to the main bronchus and rarely to larynx. The disorder is more common in men and the diagnosis is usually made in the fourth through sixth decades of life. It's etiology remains unknown, with no relationship to smoking or systemic disorders. The patients are only rarely symptomatic since severe airway obstruction is unusual. Nevertheless the clinic is characterized by cough, dyspnea and recurrent respiratory infections. Even though imaging studies and bronchoscopy may indicate the diagnosis, the diagnosis is histological. There is only symptomatic therapy available. Methods: We report a case of an 81 year old men, with past history of auricular fibrillation, hypertension and heart failure who presented with recurrent respiratory infections treated with different courses of antibiotics. He was hospitalized due to community acquired pneumonia, with fever (37.8 °C), productive cough, yellow sputum, dyspnea and wheezing. He was treated with Ceftriaxone and Clarithromycin, completing 10 days of therapy. No agent was isolated. At the time of discharge we presented only with dry cough. One week after, he was readmitted for the same symptoms. Laboratory tests revealed mild leukocytosis and slight PCR elevation. The chest X-ray revealed right pleural effusion. Blood cultureswere negative. He started broad spectrumantibioticwith Piperacillin–Tazobactam, completing 10 days. Thoracocentesis revealed exudative effusion, with negative cultures. On the control X-ray there was a reduction of the effusion. Two days after, we noticed diminished breath sounds on physical examination, so another X-ray was performed, presenting a large pleural effusion, as we saw at the beginning. Regarding the medical history of the patient, the exudative nature of the effusion we performed bronchoscopy that showed cartilaginous submucosal nodules of the tracheal submucosa, consistent with tracheobronchopathia osteochondroplastica. Conclusions: TPO is a rare entity, characterized by bony and cartilaginous submucosal nodules which project into the tracheal–bronchial lumen, being more frequent in males being in the majority of the cases asymptomatic. In our case, regarding the age of the patient and the medical history, we think that this pathology favors the recurrent respiratory infections.

Concurrence of Torus Mandibularis with Multiple Buccal Exostoses

Concurrence of Torus Mandibularis with Multiple Buccal Exostoses

Tracheobronchopathia osteochondroplastica presenting as a single dominant tracheal mass

Tracheobronchopathia osteochondroplastica is a rare, benign disorder of upper airways characterized by multiple submucosal metaplastic cartilaginous and bony nodules arising from the tracheal cartilage. We report an unusual presentation of tracheobronchopathia osteochondroplastica as a single dominant nodule arising from the anterior tracheal rings in a young adult man who presented with wheezing and symptoms of airway obstruction. The differential diagnosis of cartilaginous and bony endotracheal lesions is discussed.

Etiopathogenesis of hyperostosis frontalis interna: A mystery still

Hyperostosis frontalis interna is a morphological pattern characterized by single or multiple bony nodules situated on the inner lamina of the frontal bone. It is seldom found in males, but it is a common phenomenon among post-menopausal females in modern societies but relatively rare in antiquity. The etiopathogenesis of the trait is a matter of debate and ranges from genetic predisposition to epigenetic, while endocrine disturbances, aging, and dietary factors are also listed among the causes. We studied the frequency, characteristic features, and etiopathogenesis of the disease in recent cadaveric and dry skull specimens. The frequency of hyperostosis frontalis interna in cadavers and dry skull materials was almost identical, 12.5% and 12.3%, respectively. In cadavers, 87.5% of severe hyperostosis frontalis interna cases were found in females over 65 years-old. Interestingly, in two cadavers we found hyperostotic lesions spreading onto adjacent tissues such as the dura and falx cerebri. We provide some new aspects that may help in better understanding of the etiopathogenesis of hyperostosis frontalis interna. Thereby, we discuss the various etiopathogenesis models found in the literature.

A Case of Tracheobronchopathia Osteochondroplastica

Received November 29, 2010 Revised December 30, 2010 Accepted January 4, 2011 Address for correspondence Joon Kyoo Lee, MD, PhD Department of OtolaryngologyHead and Neck Surgery, Chonnam National University Hwasun Hospital, 160 Ilsim-ri, Hwasun-eup, Hwasun 519-763, Korea Tel +82-61-379-7760 Fax +82-61-379-7761 E-mail joonkyoo@chonnam.ac.kr Tracheobronchopathia Osteochondroplastica (TO) is a rare disease of the trachea characterized by the development of submucosal cartilaginous and bony nodules. The nodules are usually located at the anterior and lateral walls and sometims on the posterior membranous wall. Clinically, the manifestations of TO vary from the incidentally detected asymptomatic to life threatening diseases with airway obstruction. Bronchoscopy is a useful diagnostic tool and radiographic studies also play an important role in the diagnosis of TO. The treatment of TO is reserved for the symptomatic lesion with severe airway narrowing and the prevention of recurrent respiratory infections. Korean J Otorhinolaryngol-Head Neck Surg 2011;54:408-10 Key WordsZZTracheobronchopathia osteoplastica ᆞAirway obstruction.

Normally Shaped Heads With No Sutures, Normally Shaped Heads With Abnormal Sutures, and Abnormally Shaped Heads With Normal Sutures

We present a series of children whose head shapes and suture status do not make sense. There were 3 patients with complete absence of sutures and normal head shapes. One patient was evaluated for microcephaly at 6 years of age. In the second, the absence of sutures was discovered on workup for headaches at 8 years of age. The third underwent x-ray imaging for parasagittal bony nodules at 1 month of age. The head circumferences fell at the 4th, 25th, and 50th percentiles, respectively. The 2 older children were in normal classes, and the youngest was meeting milestones appropriately. We encountered 3 patients with fusion of the sagittal suture and normal head shapes. One had a flattened occiput, the second patient was thought to be brachycephalic, and the third was macrocephalic. Head circumferences were at the fourth, 50th, and 75th percentiles. The patient with head circumference at the fourth percentile had fetal alcohol syndrome and speech delay. The other 2 were developing normally with follow-up of 14 months. Finally, 3 patients underwent surgery for characteristic craniosynostotic head shapes and were found to have patent sutures at surgery. One patient had classic unilateral coronal synostosis and a patent suture on the side of the defect. The second patient had Crouzon syndrome with characteristic head shape, but open coronal sutures. The third patient had the appearance of bicoronal synostosis, with a patent suture on one side. They have had good results from their craniofacial reconstructions at 24, 12, and 6 months' follow-up. We have no explanation for these interesting findings.

Hereditary Multiple Exostoses in the Hands and Fingers: Early Presentation and Early Surgical Treatment in Family Members. Case Reports

Hereditary multiple exostosis (HME) is a benign condition with multiple bony tumors with cartilage caps (osteochondromas), mainly presenting in the long and flat bones. Usually the presentation for HME is between 2 and 10years of age and most are seen by 4years of age (Khan et al. 2009). In this paper, we report a family with three members (father, son, and a daughter) who had very early presentations of HME in the fingers within the first 2years of age. The son presented with bony nodules at 7months of age, and he required surgery at 13months of age for a severe functional deformity of his left ring finger. He also had an unusual histological presentation on his osteochondroma that consists of only subperiosteal cartilage without ossification.

An unusual cause of recurrent hemoptysis: tracheopatia osteoplastica

An otherwise healthy 55-year-old man was referred to the hospital by his general practitioner due to recurrent episodes of hemoptysis. His medical history was silent, although his working activity (textile branch) exposed him to organic dusts. Shortly after an acute bronchitis treated with aspirin, the patient had a first episode of hemoptysis. Even after aspirin withdrawal, thoracic sense of oppression and cough persisted for several days, and a second hemoptysis event occurred. Cardiothoracic physical examination was unremarkable, and his general practitioner performed electrocardiogram, chest X-ray, and blood chemistry panel (all these examinations were normal), and asked for cardiologic and otorhinolaryngoiatric consultations, with no findings of pathological remarks. Hemoptysis is a relatively common symptom of cardiopulmonary disease. Although bronchitis is a very common cause, a careful evaluation may be necessary to exclude more serious pathologic conditions, such as bronchogenic carcinoma and tuberculosis [1]. Moreover, the decision on whether to perform further investigations has not been influenced by the amount of bleeding. In fact, there is no correlation between quantity of blood and seriousness of the underlying thoracic disease [1]. In this case, given the patient’s age, his working history, the recurrence of hemoptysis episodes, and prior negative results, we decided not to dismiss hemoptysis as simply due to bronchitis, and proceed with a more advanced workup including CT scan and bronchoscopy. Thoracic high-resolution computerized tomography (HRCT) showed limited ‘‘polished glass’’ areas, localized to the posteriorbasal segments of inferior lobes. Bronchoscopy revealed the presence of multiple calcifications in the tracheobronchial cartilages, with normal mucosal surface, extending also to the larger bronchial ramifications and the carina (Fig. 1, upper and lower panels). Cultural examination and cytology of bronchoalveolar lavage were negative. The bronchoscopic picture was self-explaining, since the presence of sessile bony or cartilagineous nodules of the tracheal wall is the hallmark of tracheopatia osteoplastica. Tracheopatia osteoplastica (or tracheopatia osteochondroplastica) (TO) is an uncommon disease of the upper airways, characterized by the presence of multiple cartilaginous or bony projections into the tracheobronchial lumen [2]. It usually affects people aged [50 years, but incidence and prevalence in the general populations are unknown, since the great majority of cases are diagnosed only post-mortem [3]. The cause is unknown, and more often this disease is asymptomatic. However, the most frequent symptoms at presentation are chronic cough (54% of cases), sputum production (34%), and hemoptysis (20%) [2]. Computerized tomography may sometimes reveal tracheal soft tissue masses or beaded calcification in the tracheobronchial cartilages, although calcifications, luminal stenosis, wall thickening, and nodules need for differential diagnosis with other uncommon diseases involving the central airways, i.e., Wegener’s granulomatosis, relapsing polychondritis, amyloidosis, sarcoidosis, and tuberculosis. Thus, bronchoscopy remains the main diagnostic tool: nodules are most frequently distributed along the proximal tracheobronchial tree, especially in the upper and middle S. Savelli M. L. Grata A. Ricci S. Gamberini R. Manfredini (&) U.O. di Medicina Interna, Ospedale del Delta, Azienda U.S.L. di Ferrara, Ferrara, Italy e-mail: r.manfredini@ausl.fe.it

A biaxial rotating bioreactor for the culture of fetal mesenchymal stem cells for bone tissue engineering

The generation of effective tissue engineered bone grafts requires efficient exchange of nutrients and mechanical stimulus. Bioreactors provide a manner in which this can be achieved. We have recently developed a biaxial rotating bioreactor with efficient fluidics through in-silico modeling. Here we investigated its performance for generation of highly osteogenic bone graft using polycaprolactone–tricalcium phosphate (PCL–TCP) scaffolds seeded with human fetal mesenchymal stem cell (hfMSC). hfMSC scaffolds were cultured in either bioreactor or static cultures, with assessment of cellular viability, proliferation and osteogenic differentiation in vitro and also after transplantation into immunodeficient mice. Compared to static culture, bioreactor-cultured hfMSC scaffolds reached cellular confluence earlier (day 7 vs. day 28), with greater cellularity (2×, p < 0.01), and maintained high cellular viability in the core, which was 2000 μm from the surface. In addition, bioreactor culture was associated with greater osteogenic induction, ALP expression (1.5× p < 0.01), calcium deposition (5.5×, p < 0.001) and bony nodule formation on SEM, and in-vivo ectopic bone formation in immunodeficient mice (3.2×, p < 0.001) compared with static-cultured scaffolds. The use of biaxial bioreactor here allowed the maintenance of cellular viability beyond the limits of conventional diffusion, with increased proliferation and osteogenic differentiation both in vitro and in vivo, suggesting its utility for bone tissue engineering applications.