Velopharyngeal dysfunction and speech-related characteristics in craniofacial microsomia: a retrospective analysis of 223 patients.

This study aimed to document the prevalence, severity, and risk factors of velopharyngeal dysfunction (VPD) in craniofacial microsomia (CFM) and to analyse differences in VPD-related speech characteristics between CFM patients without cleft lip and/or palate (CL/P), CFM patients with CL/P, and CL/P patients without CFM (control). A total of 223 patients with CFM were included, of whom 59 had a CL/P. Thirty-four CFM patients had VPD, including 20 with a CL/P. VPD was significantly more prevalent in CFM with CL/P than in CFM without CL/P (odds ratio (OR) 4.1, 95% confidence interval (CI) 1.9-8.7; P < 0.001). Multivariate logistic regression showed a significant association between CL/P and VPD in CFM patients (OR 7.4, 95% CI 2.1-26.3; P = 0.002). The presence of VPD was not associated with sex, the laterality or severity of CFM. Speech problems related to VPD appeared to be similar among the different groups (CFM without CL/P, CFM with CL/P, CL/P without CFM). As 15.2% of all CFM patients and 8.5% of CFM patients without CL/P had VPD, it is proposed that all patients with CFM, with or without CL/P, should be assessed by a speech and language therapist for the potential risk of VPD.

Hyoid bone morphology in patients with isolated robin sequence - A case-control study utilizing 3D morphable models.

Background: Abnormalities of the hyoid bone are associated with impairment of oropharyngeal functions including feeding, swallowing, and breathing. Few studies have characterized anatomic abnormalities of the hyoid in patients with Robin sequence (RS), e.g. a less mineralized and voluminous hyoid. The purpose of this study was to compare normal hyoid bone morphology and hyoid bone morphology in children with isolated RS. Methods: Three-dimensional (3D) reconstructions of the hyoid bone were obtained from CT-imaging of children with RS and unaffected controls. A 3D morphable model was constructed using Principal Component Analysis (PCA). Partial least squares - Discriminant Analysis (PLS-DA) and multivariate analysis of variance (MANOVA) were used to characterize and compare hyoid shape differences between patients with RS and an age-matched control group. Results: The study included 23 subjects with RS (mean age 9.8 ± 10.3 months) and 46 age-matched control samples. A less voluminous hyoid was observed for the RS group with a larger lateral divergence of the greater horns compared to controls (MANOVA, p-value<0.001). The first shape variable from the PLS-DA model showed a significant correlation for the observed variance between the two groups (Spearman R = -0.56, p-value<0.001). The control samples and 151 CT-scans of subjects up to age 4 years were used to create a 3D morphable model of normal hyoid shape variation (n = 197, mean age 22.1 ± 13.1 months). For the normal 3D morphable model, a high degree of allometric shape variation was observed along the first principal component. Conclusions: The 3D morphable models provide a comprehensive and quantitative description of variation in normal hyoid bone morphology, and allow detection of distinct differences between patients with isolated RS and controls.

Healthcare use and direct medical costs in a cleft lip and palate population: an analysis of observed and protocolized care and costs.

This study was performed to describe observed healthcare utilization and medical costs for patients with a cleft, compare these costs to the expected costs based on the treatment protocol, and explore the additional costs of implementing the International Consortium for Health Outcomes Measurement (ICHOM) Standard Set for Cleft Lip and Palate (CL/P). Forty patients with unilateral CL/P between 0 and 24 years of age, treated between 2012 and 2019 at Erasmus University Medical Center, were included. Healthcare services (consultations, diagnostic and surgical procedures) were counted and costs were calculated. Expected costs based on the treatment protocol were calculated by multiplying healthcare products by the product prices. Correspondingly, the additional expected costs after implementing the ICHOM Standard Set (protocol + ICHOM) were calculated. Observed costs were compared with protocol costs, and the additional expected protocol + ICHOM costs were described. The total mean costs were highest in the first year after birth (€5596), mainly due to surgeries. The mean observed total costs (€40,859) for the complete treatment (0-24 years) were 1.6 times the expected protocol costs (€25,198) due to optional, non-protocolized procedures. Hospital admissions including surgery were the main cost drivers, accounting for 42% of observed costs and 70% of expected protocol costs. Implementing the ICHOM Standard Set increased protocol-based costs by 7%.

The Esthetic Perception of Morphological Severity in Scaphocephalic Patients is Correlated With Specific Head Geometrical Features.

OBJECTIVE: To investigate the relationship between perception of craniofacial deformity, geometric head features, and 3D head shape analyzed by statistical shape modeling (SSM). PATIENTS: A total of 18 unoperated patients with scaphocephaly (age = 5.2 ± 1.1m)-6 were followed-up after spring-assisted cranioplasty (SAC) (age = 9.6 ± 1.5m)-and 6 controls (age = 6.7 ± 2.5m). MAIN OUTCOME MEASURES: 3D head shapes were retrieved from 3D scans or computed tomography (CTs). Various geometrical features were measured: anterior and posterior prominence, take-off angle, average anterior and posterior lateral and horizontal curvatures, cranial index (CI) (cranial width over length), and turricephaly index (TI) (cranial height over length). SSM and principal component analysis (PCA) described shape variability. All models were 3D printed; the perception of deformity was blindly scored by 9 surgeons and 1 radiologist in terms of frontal bossing (FB), occipital bulleting (OB), biparietal narrowing (BN), low posterior vertex (LPV), and overall head shape (OHS). RESULTS: A moderate correlation was found between FB and anterior prominence (r = 0.56, P < .01) and take-off angle (r = - 0.57, P < .01). OB correlated with average posterior lateral curvature (r = 0.43, P < 0.01) similarly to BPN (r = 0.55, P < .01) and LPV (r = 0.43, P < .01). OHS showed strong correlation with CI (r = - 0.68, P < .01) and TI (r = 0.63, P< .01). SSM Mode 1 correlated with OHS (r = 0.66, p < .01) while Mode 3 correlated with FB (r = - 0.58, P < .01). CONCLUSIONS: Esthetic cranial appearance in craniofacial patients is correlated to specific geometric parameters and could be estimated using automated methods such as SSM.

Acceptability and feasibility of an online psychosocial intervention for Dutch adolescents with a visible difference: A mixed-methods study.

Adolescents with a visible difference can experience difficult social situations, (e.g., people staring or making unwanted comments) and are at risk for mental health problems. Unfortunately, interventions for adolescents with a visible difference experiencing appearance-related distress are scarce and lack an evidence-base. This study tests the acceptability and feasibility of YP Face IT, an innovative online psychological intervention using social skills training and cognitive behavioural therapy, to Dutch adolescents. Adolescents aged 12-17 with a visible difference and access to an internet-enabled computer or tablet participated. They completed YP Face IT (eight sessions) and questionnaires were administered pre- and post-intervention. After completing YP Face IT, participants were interviewed to assess the acceptability and feasibility of YP Face IT and study procedures. Overall, 15 adolescents consented to participation, one person dropped out after one session. Most adolescents appreciated the intervention and all would recommend it to other adolescents experiencing appearance-related distress. Everyone reported learning experiences after following the sessions. Some struggled with motivation, but reminders by the website and research team were helpful. The Dutch YP Face IT intervention may be acceptable and the current study design is feasible to use. An RCT should be conducted to assess the effectiveness of the intervention.

Hearing impairment and ear anomalies in craniofacial microsomia: a systematic review.

The aim of this systematic review was to review the literature on hearing impairment and ear anomalies in patients with craniofacial microsomia and to determine their prevalence. Sixty-two records including 5122 patients were included. Ear anomalies were present in 52-100% of patients. The most reported external ear malformations were microtia, pre-auricular tags, and atresia of the external auditory canal. Ossicular anomalies were the most reported middle ear malformations, whereas the most reported inner ear malformations included oval window anomalies, cochlear anomalies, and anomalies of the semicircular canals. Hearing loss in general was reported in 29-100% of patients, which comprised conductive hearing loss, mixed hearing loss, and sensorineural hearing loss. Between 21% and 51% of patients used hearing aids, and 58% underwent a surgical intervention to improve hearing. The relationship between different phenotypes of craniofacial microsomia and the type and severity of hearing loss is mostly unclear. In conclusion, the high prevalence of ear and hearing anomalies in patients with craniofacial microsomia underlines the importance of audiological screening in order to facilitate individual treatment.

CT parameters in pure orbital wall fractures and their relevance in the choice of treatment and patient outcome: a systematic review.

Computed tomography (CT) is commonly used for the diagnosis, treatment planning, and prognosis of pure orbital fractures of the orbital floor and medial wall. The aim of this study was to systematically review the current literature in order to establish an overview of CT parameters relevant to the choice of treatment and (long-term) clinical outcome for patients treated operatively and conservatively. The PRISMA guidelines were followed. Databases were searched using the terms 'orbital fracture' and 'computed tomography'. Studies evaluating the relationship between CT parameters and the treatment decision or clinical outcome (enophthalmos, diplopia, and/or limitation of ocular movement) were included. The search yielded 4448 results of which 31 were included (except for three, all were retrospective). The systematic use of CT imaging in orbital fractures of the floor and the medial wall can be of great value in the treatment decision and prediction of (long-term) clinical outcomes for both conservatively and surgically treated patients. The following parameters were found to be the most relevant: fracture size, fracture location, orbital volume, soft tissue involvement, and craniocaudal dimension. Although some show great individual potential, it is likely that incorporating all parameters into an algorithm will provide the best predictive power and thus would be the most practically applicable tool.

Feeding and swallowing outcomes following mandibular distraction osteogenesis: an analysis of 22 non-isolated paediatric cases.

Patients with mandibular hypoplasia and upper airway obstruction are at an increased risk of feeding and swallowing difficulties. Little has been described regarding these outcomes following mandibular distraction. The aim of this study was to evaluate the effect of mandibular distraction on feeding and swallowing function. A retrospective study was performed on 22 patients with non-isolated mandibular hypoplasia and severe upper airway obstruction treated with mandibular distraction. Median age at first mandibular distraction was 3.1 years (interquartile range 2.3-6.0 years) and the median follow-up time was 3.5 years (interquartile range 2.0-9.4 years). Prior to mandibular distraction, feeding difficulties were present in 18 patients. Swallowing difficulties were present in 20 patients, all of whom had problems in the oral phase of swallowing, while 11 patients had additional problems in the pharyngeal phase. Following mandibular distraction, at the time of follow-up, feeding difficulties persisted in 13 patients. Swallowing difficulties in the oral phase remained present in all 20 patients, while pharyngeal phase problems persisted in seven patients. In conclusion, feeding and swallowing difficulties are highly prevalent in non-isolated patients and often persist following mandibular distraction. Moreover, these can be the reason that decannulation cannot be accomplished. Hence, awareness and close follow-up by a specialized speech therapist is of paramount importance.

[Green tooth discoloration in a two-year-old boy]. / Groene tandverkleuring bij een peuter.

Green tooth discoloration can have several causes. From the patient history of the two-year-old with green tooth discoloration clear causal relationships can be identified. The pathological cause is an increase in bilirubin levels for an extended period of time. Determining the extent of tooth development in combination with the increase in bilirubin levels makes it possible to estimate the degree and pattern of green tooth discoloration. If the increase in bilirubin levels is short-lived, it is possible the permanent dentition will not be affected.

A rare complication of an Arteriovenous shunt after bimaxillary surgery.

The most common complications following bimaxillary surgery are inferior alveolar nerve damage, hemorrhage, and relapse. Severe complications are rare, but few cases of vascular arteriovenous malformation, cavernous sinus thrombosis, formation of an aneurysm or arteriovenous shunting are reported in literature. We present a case of a 20-year-old male patient who developed a right sided tinnitus and visible pulsations close to the mandibular angle on the right side after bimaxillary surgery. CT-angiography and subsequent digital subtraction angiography (DSA) six months after surgery showed an arteriovenous fistula (AVF) from the external carotid artery to the external jugular vein. The AVF was treated by endovascular coil embolization. At six months after intervention there were no residual complaints. We discuss the possible etiology and trauma mechanisms that might have caused this pathology and present recommendations to avoid this type of complications.

Ocular and adnexal anomalies in craniofacial microsomia: Type and prevalence in a multicentre cohort study.

The aim of this multicentre retrospective cohort study was to describe and categorize the types of ocular and adnexal anomalies seen in patients with craniofacial microsomia (CFM) and to determine their prevalence. In addition, the relationship between the OMENS-Plus and Pruzansky-Kaban classification for each patient and the presence of ocular anomalies was investigated. A total of 881 patients with CFM from four different craniofacial centres were included. Data on ocular anomalies were gathered from the patient charts. Ocular anomalies were present in 33.9% of patients. Four subgroups of ocular and adnexal anomalies were identified. Type I ocular anomalies were present in 22.2%, type II in 19.0%, type III in 18.4%, and type IV in 14.5%. Several potentially preventable and treatable ocular anomalies were identified. Higher OMENS-Plus classification orbit and soft tissue scores and Pruzansky-Kaban classification mandible scores were associated with an increased risk of ocular anomalies. Based on these results and the clinical implications ocular anomalies may have, we underline the importance of targeted ophthalmological screening in CFM. Healthcare professionals should be aware of the possibility of ocular anomalies in these patients, especially during the critical period for visual development.

Extracraniofacial anomalies in Treacher Collins syndrome: A multicentre study of 248 patients.

Treacher Collins syndrome (TCS) is a congenital malformation of the craniofacial structures derived from the first and second pharyngeal arches. The craniofacial deformities are well described in the literature. However, little is known about whether there are associated extracraniofacial anomalies. A retrospective study was conducted using data from four craniofacial units. Medical charts were reviewed for the presence and type of extracraniofacial anomalies, as well as age at diagnosis. A possible correlation between the severity of the phenotype and the presence of extracraniofacial anomalies was assessed using the Hayashi classification. A total of 248 patients with TCS were identified; 240 were confirmed to have TCS, of whom 61 (25.4%) were diagnosed with one or more extracraniofacial anomalies. Ninety-five different extracraniofacial anomalies were found; vertebral (n=32) and cardiac (n=13) anomalies were most frequently seen, followed by reproductive system (n=11), central nervous system (n=7), and limb (n=7) anomalies. No correlations between tracts were found. Extracraniofacial anomalies were more prevalent in these patients with TCS compared to the general population (25.4% vs 0.001-2%, respectively). Furthermore, a positive trend was seen between the severity of the syndrome and the presence of extracraniofacial anomalies. A full clinical examination should be performed on any new TCS patient to detect any extracraniofacial anomalies on first encounter with the craniofacial team.

Parenting Children With a Cleft Lip With or Without Palate or a Visible Infantile Hemangioma: A Cross-Sectional Study of Distress and Parenting Stress.

OBJECTIVE: Parents of children with a medical condition and a visible difference can experience challenging situations. We evaluated distress and parenting stress in parents of children with a cleft lip with or without cleft palate (CL±P) or a visible infantile hemangioma (IH). SETTING: This cross-sectional study took place in an academic medical hospital in Rotterdam, the Netherlands. PARTICIPANTS: Three-hundred nine parents (mean age = 40.30, 56.00% mothers) of children with CL±P and 91 parents (mean age = 36.40, 58.24% mothers) of children with IH. MAIN OUTCOME MEASURES: The Dutch version of the Parenting Stress Index - Short Form and the subscales Anxiety, Depression, and Hostility of the Symptom Checklist - 90. RESULTS: One sample t tests and mixed linear modeling were used. On average, parents of children with CL±P and of children with IH showed significantly lower parenting stress compared to normative data. Anxiety was significantly lower in parents of children with CL±P than that in the norm group. Visibility of the condition was not related to distress or parenting stress. Child behavioral problems were positively related to parenting stress, depression, and hostility. CONCLUSIONS: Parents of children with CL±P and IH report less distress and parenting stress compared to the norm. On average, these parents seem well adjusted. A practical implication is to monitor parents of children with behavioral problems.

Functional outcomes in patients with facial dysostosis and severe upper airway obstruction.

An increased risk of upper airway obstruction (UAO) is seen in up to 95% of patients with facial dysostosis. Secondary to respiratory problems are feeding difficulties and increased nutritional requirements. Little has been described regarding these outcomes in this patient population. Hence, a retrospective cohort study was performed to gather data on functional outcomes. Eighteen patients with facial dysostosis and severe UAO were included. The median follow-up time was 3.42 years. A tracheostomy tube was placed in 13 patients, of whom 10 subsequently underwent mandibular distraction. Three of the five patients without a tracheostomy underwent mandibular distraction as the primary surgical treatment; the remaining two patients were treated conservatively with oxygen supplementation. At presentation, 13 patients had feeding difficulties. Overall malnutrition was present in 16 patients during follow-up. At the end of follow-up, severe UAO was present in 12 patients, feeding difficulties in seven patients, and malnutrition in four patients, while two patients died. In conclusion, patients with facial dysostosis have a high prevalence of severe UAO, feeding difficulties, and malnutrition. Importantly, mandibular distraction has limited success in treating severe UAO in these patients. Close follow-up by a specialized craniofacial team is of paramount importance to manage the long-term consequences.

Undetected anomalies in foetuses with a prenatal diagnosis of isolated cleft.

The aim of this study was to determine the rate of undetected additional anomalies following a prenatal diagnosis of isolated oral cleft. Data of all infants with a prenatal diagnosis of isolated oral cleft born between 2000 and 2015 were studied retrospectively. Additional anomalies detected after birth were categorized as minor or major and included structural and chromosomal anomalies. Isolated clefts of the lip (CL), lip and alveolus (CLA) and lip, alveolus, and palate (CLAP) were diagnosed prenatally in 176 live-born infants. The type of cleft was more extensive after birth in 34/176 (19.3%) and less extensive in 16/176 (9.1%) newborns. Additional anomalies were diagnosed in 24 infants (13.6%), of which 12 (6.8%) were categorized as major. The latter included two submicroscopic chromosome anomalies and two gene mutations. Postnatal additional anomalies occurred more frequently in CLA and CLAP than in CL, and more in bilateral than in unilateral clefts. Major anomalies are still found in infants with a prenatal diagnosis of an isolated oral cleft. The prevalence of additional anomalies seems to be related to the type and bilaterality of the cleft, and this should be considered during prenatal counselling.

Ocular and adnexal anomalies in craniofacial microsomia: a systematic review.

Ocular anomalies may occur in craniofacial microsomia (CFM). The aim of this systematic review was to review the literature on ocular anomalies and their incidence, in order to estimate the need for ophthalmological screening in CFM patients. Online databases were searched, and data on the number of patients, type and incidence of ocular anomalies, and visual acuity were extracted. Four subgroups of ocular and adnexal anomalies were identified, to provide an overview of the different anomalies. Twenty-five papers analysing 1419 patients in total were included. Ocular anomalies were documented in 6.7-100% of patients. The most reported type I ocular anomalies were eyelid coloboma, lipodermoids, and orbital dystopia. The most reported type II ocular anomalies were epibulbar dermoid, microphthalmia, and anophthalmia. Ptosis and strabismus were the most reported type III anomalies, and irregular astigmatism was the most reported type IV ocular anomaly. Visual impairment in general was reported in 8-71.4% of patients, with severe visual impairment in 11.1-71.4% and amblyopia in 16.3%. This study provides a detailed overview of ocular anomalies in CFM and their prevalence. Furthermore, we propose a new classification to organize ocular anomalies into four clinically relevant subtypes. Finally, the high prevalence of ocular anomalies and visual impairment in this study suggests that CFM patients should undergo ophthalmological screening at least once during the sensitive period.

Anxiety and depression in adolescents with a visible difference: A systematic review and meta-analysis.

Living with a visible difference can entail challenging social situations, associated with psychosocial symptoms. However, it is not clear whether adolescents with a visible difference experience more anxiety and depression than unaffected peers. We aim to determine whether adolescents with a visible difference experience more symptoms of anxiety and depression than unaffected peers. A literature search was conducted in Embase, Medline Ovid, Web of Science, Cochrane CENTRAL, PsycINFO Ovid, and Google Scholar. Meta-analyses were done using random-effects models to calculate a standardised mean difference. Analyses for subgroups were used to study causes of visible difference. Eleven studies were identified (n = 1075, weighted mean age = 15.80). Compared to unaffected peers, adolescents with a visible difference experience more symptoms of anxiety (SMD = 0.253, 95 % CI [0.024, 0.482], p = .030), but not depression (SMD = 0.236, 95 % CI [-0.126, 0.599], p = .202). Adolescents with a skin condition did not experience more symptoms of anxiety (SMD = 0.149, 95 % CI [-0.070, 0.369], p = .182) or depression (SMD = 0.090, 95 % CI [-0.082, 0.262], p = .305) when compared to unaffected peers. Overall, more symptoms of anxiety are found in adolescents with a visible difference compared to peers. No differences in anxiety or depression were found for skin differences. Screening for anxiety is recommended.

A comparison of airway interventions and gastrostomy tube placement in infants with Robin sequence.

The purpose of this study was to evaluate feeding impairment following non-operative or operative management of airway obstruction in a large series of infants with Robin sequence (RS) by rate of G-tube placement. A retrospective study was conducted at Boston Children's Hospital including 225 patients (47.1% female) with RS treated between 1976 and 2018. Subjects were grouped by intervention required for successful management of airway obstruction: non-operative only (n = 120), tongue-lip adhesion (TLA, n = 75), mandibular distraction osteogenesis (MDO, n = 21), or tracheostomy (n = 9). The operative group had a higher rate of G-tube placement (58.1%) than the non-operative group (28.3%, P < 0.0001). Subjects in the TLA and tracheostomy groups had higher odds of G-tube placement than subjects in the MDO group: odds ratio (OR) 5.5 (95% confidence interval (CI) 1.8-17.3, P = 0.004) and OR 27.0 (95% CI 3.2-293.4, P = 0.007), respectively. Syndromic patients and those with gastrointestinal anomalies also had higher odds of G-tube placement: OR 3.5 (95% CI 1.7-7.2, P = 0.001) and OR 5.9 (95% CI 1.6-21.0, P = 0.007), respectively. Infants with RS who require an airway operation and those with a syndromic diagnosis or gastrointestinal anomalies are more likely to require placement of a G-tube. Of the operative groups, MDO was associated with the lowest G-tube rate, compared to TLA and tracheostomy.

Intracranial actinomycosis of odontogenic origin masquerading as auto-immune orbital myositis: a fatal case and review of the literature.

BACKGROUND: Actinomycetes can rarely cause intracranial infection and may cause a variety of complications. We describe a fatal case of intracranial and intra-orbital actinomycosis of odontogenic origin with a unique presentation and route of dissemination. Also, we provide a review of the current literature. CASE PRESENTATION: A 58-year-old man presented with diplopia and progressive pain behind his left eye. Six weeks earlier he had undergone a dental extraction, followed by clindamycin treatment for a presumed maxillary infection. The diplopia responded to steroids but recurred after cessation. The diplopia was thought to result from myositis of the left medial rectus muscle, possibly related to a defect in the lamina papyracea. During exploration there was no abnormal tissue for biopsy. The medial wall was reconstructed and the myositis responded again to steroids. Within weeks a myositis on the right side occurred, with CT evidence of muscle swelling. Several months later he presented with right hemiparesis and dysarthria. Despite treatment the patient deteriorated, developed extensive intracranial hemorrhage, and died. Autopsy showed bacterial aggregates suggestive of actinomycotic meningoencephalitis with septic thromboembolism. Retrospectively, imaging studies showed abnormalities in the left infratemporal fossa and skull base and bilateral cavernous sinus. CONCLUSIONS: In conclusion, intracranial actinomycosis is difficult to diagnose, with potentially fatal outcome. An accurate diagnosis can often only be established by means of histology and biopsy should be performed whenever feasible. This is the first report of actinomycotic orbital involvement of odontogenic origin, presenting initially as bilateral orbital myositis rather than as orbital abscess. Infection from the upper left jaw extended to the left infratemporal fossa, skull base and meninges and subsequently to the cavernous sinus and the orbits.

Collagen type X is essential for successful mesenchymal stem cell-mediated cartilage formation and subsequent endochondral ossification.

in tissue engineering, endochondral ossification (EO) is often replicated by chondrogenically differentiating mesenchymal stromal cells (MSCs) in vitro and achieving bone formation through in vivo implantation. The resulting marrow-containing bone constructs are promising as a treatment for bone defects. However, limited bone formation capacity has prevented them from reaching their full potential. This is further complicated since it is not fully understood how this bone formation is achieved. Acellular grafts derived from chondrogenically differentiated MSCs can initiate bone formation; however, which component within these decellularised matrices contribute to bone formation has yet to be determined. Collagen type X (COLX), a hypertrophy-associated collagen found within these constructs, is involved in matrix organisation, calcium binding and matrix vesicle compartmentalisation. However, the importance of COLX during tissue-engineered chondrogenesis and subsequent bone formation is unknown. The present study investigated the importance of COLX by shRNA-mediated gene silencing in primary MSCs. A significant knock-down of COLX disrupted the production of extracellular matrix key components and the secretion profile of chondrogenically differentiated MSCs. Following in vivo implantation, disrupted bone formation in knock-down constructs was observed. The importance of COLX was confirmed during both chondrogenic differentiation and subsequent EO in this tissue engineered setting.