A multicenter, open-label, randomized, phase II study of cediranib with or without lenalidomide in iodine 131-refractory differentiated thyroid cancer.

BACKGROUND: Multitargeted tyrosine kinase inhibitors (TKIs) of the vascular endothelial growth factor receptor (VEGFR) pathway have activity in differentiated thyroid cancer (DTC). Lenalidomide demonstrated preliminary efficacy in DTC, but its safety and efficacy in combination with VEGFR-targeted TKIs is unknown. We sought to determine the safety and efficacy of cediranib, a VEGFR-targeted TKI, with or without lenalidomide, in the treatment of iodine 131-refractory DTC. PATIENTS AND METHODS: In this multicenter, open-label, randomized, phase II clinical trial, 110 patients were enrolled and randomized to cediranib alone or cediranib with lenalidomide. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate, duration of response, toxicity, and overall survival (OS). Patients (≥18 years of age) with DTC who were refractory to further surgical or radioactive iodine (RAI) therapy as reviewed at a multispecialty tumor board conference, and evidence of disease progression within the previous 12 months and no more than one prior line of systemic therapy were eligible. RESULTS: Of the 110 patients, 108 started therapy and were assessable for efficacy. The median PFS was 14.8 months [95% confidence interval (CI) 8.5-23.8 months] in the cediranib arm and 11.3 months (95% CI 8.7-18.9 months) in the cediranib with lenalidomide arm (P = 0.36). The 2-year OS was 64.8% (95% CI 43.3% to 86.4%) and 75.3% (95% CI 59.4% to 91.0%), respectively (P = 0.80). The serious adverse event rate was 41% in the cediranib arm and 46% in the cediranib with lenalidomide arm. CONCLUSIONS: Single-agent therapy with cediranib showed promising efficacy in RAI-refractory DTC similar to other VEGFR-targeted TKIs, while the addition of lenalidomide did not result in clinically meaningful improvements in outcomes.

[Is there more to hypodontia then missing teeth?] / Ernstige hypodontie: meer dan alleen ontbrekende gebitselementen?

Dental care professionals regularly see patients with hypodontia. Hypodontia can be acquired, for example through chemotherapy or radiation at a young age, but is hereditary in most patients. Due to an error (pathogenic variant) in one of the many genes that control odontogenesis, the formation of the tooth germ is disrupted at an early stage. The genes involved are not only crucial for tooth development, but they also play an important role in other physical processes. This article provides background information on hypodontia. Based on an inventory of gastrointestinal complaints in patients with hypodontia and a case description of the simultaneous occurrence of a coagulation disorder and hypodontia, the importance of a broad view of this patient group is illustrated. It is concluded that, in addition to a dental assessment, examination of these patients should include a limited physical examination and the medical history of the patient and his close relatives.

A Novel Method for Quantitative Three-Dimensional Analysis of Zygomatico-Maxillary Complex Symmetry.

OBJECTIVE: To develop a reliable and accurate method to quantify the symmetry of the zygomaticomaxillary complex (ZMC). METHODS: Virtual three-dimensional models were created from 53 computed-tomography scans: 15 healthy cases without maxillofacial disorders and 38 patients with ZMC fractures requiring surgical treatment.Asymmetry of the ZMC was measured using a mirroring and surface-based matching technique that uses the anterior cranial fossa as reference to determine the symmetrical position of the ZMC. The measure for ZMC asymmetry was defined as mean surface distance (MSD) between the ZMC-surface and the symmetrical position.Reliability of the method was tested in the 15 healthy cases. Inter-and intra-observer correlation coefficients (Ce) and variabilities were assessed. Accuracy was assessed by comparing ZMC asymmetry between healthy and ZMC fracture cases, and by assessing correlation of ZMC fracture severity with ZMC asymmetry. RESULTS: The average MSD of the 15 healthy cases was 1.40 ± 0.54 mm and the average MSD of the 38 ZMC fracture cases was 2.69 ± 0.95 mm ( P < 0.01). Zygomaticomaxillary complex asymmetry correlated with fracture severity ( P = 0.01). Intra-rater CC was 0.97 with an intra-rater variability of 0.09 ± 0.11 mm. Inter-rater Ce was 0.95 with an inter-rater variability of 0.12 ± 0.13 mm. CONCLUSIONS: Our method is reliable and accurate for quantitative three-dimensional analysis of ZMC-symmetry. It takes into account asymmetry caused by the shape of the ZMC as well as asymmetry caused by the position of the ZMC. CLINICAL RELEVANCE: This method is useful for the evaluation of ZMC asymmetry associated with congenital and acquired disorders of craniofacial skeleton, for surgical planning and for evaluation of postoperative results.

[Reconstruction of the mandible after loss of the middle segment due to an odontogenic myxoma]. / Reconstructie van de mandibula na verlies van het middensegment door een odontogeen myxoom.

In an 18-year-old boy, the middle segment of the mandible was removed because of a locally aggressive tumour. The reconstruction became infected and was lost, resulting in 2 separately-moving mandible parts and oral disability. For the second reconstruction, skeletal fixation with osteosynthesis plates, dental fixation with a stabilization frame and intermaxillary fixation were used. Preparation for returning the jaws to their original position was facilitated by three-dimensional simulation software. After a successful second reconstruction, an implant-supported removable bridge was eventually placed.

The chondrogenic differentiation potential of dental pulp stem cells.

Dental pulp stem cells (DPSCs) are particularly promising for tissue engineering (TE) due to the ease of their isolation procedure, great expansion potential and capability to differentiate towards several cell types of the mesodermal, ectodermal and endodermal lineages. Although several studies hint that DPSCs exhibit potential for cartilage tissue formation, the chondrogenic potential of DPSCs has only been marginally explored. Thus, the aim of the present study was to closely investigate the chondrogenic differentiation capacity of DPSCs for TE applications. More specifically, the potential of DPSCs for engineering hyaline and fibrous cartilage was determined. DPSCs obtained from 7 human molars were expanded and chondrogenically differentiated in a 3D pellet culture model. After 21 d of differentiation with chondrogenic stimuli, DPSCs displayed glycosaminoglycan, aggrecan and limited collagen type II deposition. Cells presented an elongated morphology and produced a collagen-rich extracellular matrix, with a predominance of collagen type I in most of the samples, a characteristic of fibrous cartilage tissue. Variations in the administration periods of several chondro-inductive growth factors, including transforming growth factor beta 3, bone morphogenetic protein-2, -6, -7 and insulin-like growth factor-1, did not increase glycosaminoglycan or collagen type II deposition, typical markers of hyaline cartilage tissue. Furthermore, DPSCs could not be stimulated to go into hypertrophic chondrogenesis. These results indicated that under a large variety of chondro-inductive culture conditions, DPSCs could form fibrocartilaginous tissues but not hyaline cartilage. Thus, DPSCs represent a valuable cell source for the regeneration of fibrocartilage in joints.

[Prophylaxis with antibiotics after radiotherapy in the head and neck area]. / AB-profylaxe na radiotherapie in het hoofd-halsgebied.

A side effect of radiotherapy in the head and neck area is a reduction of the capillary blood flow and with it, a reduction in local defenses. Depending on the duration and intensity of the radiation, hypoxia, hypocellularity and hypovascularity, may occur, resulting in an increased risk of infection. Hyposalivation, a commonly occurring phenomenon after radiotherapy, leads to a higher caries sensitivity. To keep oral health at an acceptable level as much as possible, teeth are checked by a dentist prior to radiotherapy. Non-essential teeth and teeth with pathology are extracted, in order to prevent future problems. Dental treatment in the area treated with radiation will nevertheless sometimes be necessary after radiotherapy. Because the risk of infection is high and may result in the loss of part of the jaw, antibiotic prophylaxis is started prior to invasive treatment. In general, amoxicillin 500 mg 3dd 1 is chosen for 14 days. After treatment, wound healing should be checked by the specialist.

Engineering of a complex bone tissue model with endothelialised channels and capillary-like networks.

In engineering of tissue analogues, upscaling to clinically-relevant sized constructs remains a significant challenge. The successful integration of a vascular network throughout the engineered tissue is anticipated to overcome the lack of nutrient and oxygen supply to residing cells. This work aimed at developing a multiscale bone-tissue-specific vascularisation strategy. Engineering pre-vascularised bone leads to biological and fabrication dilemmas. To fabricate channels endowed with an endothelium and suitable for osteogenesis, rather stiff materials are preferable, while capillarisation requires soft matrices. To overcome this challenge, gelatine-methacryloyl hydrogels were tailored by changing the degree of functionalisation to allow for cell spreading within the hydrogel, while still enabling endothelialisation on the hydrogel surface. An additional challenge was the combination of the multiple required cell-types within one biomaterial, sharing the same culture medium. Consequently, a new medium composition was investigated that simultaneously allowed for endothelialisation, capillarisation and osteogenesis. Integrated multipotent mesenchymal stromal cells, which give rise to pericyte-like and osteogenic cells, and endothelial-colony-forming cells (ECFCs) which form capillaries and endothelium, were used. Based on the aforementioned optimisation, a construct of 8 × 8 × 3 mm, with a central channel of 600 µm in diameter, was engineered. In this construct, ECFCs covered the channel with endothelium and osteogenic cells resided in the hydrogel, adjacent to self-assembled capillary-like networks. This study showed the promise of engineering complex tissue constructs by means of human primary cells, paving the way for scaling-up and finally overcoming the challenge of engineering vascularised tissues.

[An infected necrosis of the chin]. / Geïnfecteerde necrose van de kin.

A 51-year-old man was referred by his dentist to a maxillofacial surgeon with complaints of illness and pain in the mandible, associated with a rapidly expanding area of black gingiva and mucosa surrounding the lower front teeth. Clinically and radiographically there was evidence of an infected necrosis of the chin and floor of mouth. Following debridement at the operating room, the patient was treated at the intensive care unit for septic shock leading to prolonged hospitalisation. Investigation of the bone marrow did not provide an explanation for pancytopenia or the severity of the illness. In addition, genetic investigation of thiopurine S-methyltransferase gene showed no mutations. This gene codes for an identically named protein enzyme that contributes in the metabolising of the medicine azathioprine, used daily for an autoimmune disease. A combination of the use of azathioprine, a folic acid deficiency and sepsis led to this exceptional course of illness. Therapeutic intervention consisted of surgical debridement and treatment of the bacteraemia. Afterwards several corrective surgeries were necessary to restore oral functions.

New method for analysing spatial relationships of facial muscles on MRI: a pilot study.

Dysfunction of the facial musculature can have significant physical, social, and psychological consequences. In surgeries such as cleft surgery or craniofacial bimaxillary osteotomies, the perioral facial muscles may be detached or severed, potentially altering their functional vectors and mimicry capabilities. Ensuring correct reconstruction and maintenance of anatomical sites and muscle vectors is crucial in these procedures. However, a standardized method for perioperative assessment of the facial musculature and function is currently lacking. The aim of this study was to develop a workflow to analyse the three-dimensional vectors of the facial musculature using magnetic resonance imaging (MRI) scans. A protocol for localizing the origins and insertions of these muscles was established. The protocol was implemented using the 3DMedX computer program and tested on 7 Tesla MRI scans obtained from 10 healthy volunteers. Inter- and intra-observer variability were assessed to validate the protocol. The absolute intra-observer variability was 2.6 mm (standard deviation 2.0 mm), and absolute inter-observer variability was 2.6 mm (standard deviation 1.5 mm). This study presents a reliable and reproducible method for analysing the spatial relationships and functional significance of the facial muscles. The workflow developed facilitates perioperative assessment of the facial musculature, potentially aiding clinicians in surgical planning and potentially enhancing the outcomes of midface surgery.

The average three-dimensional face for different sex and age groups in a Dutch population.

The increasing use of three-dimensional imaging calls for reference models representing large parts of the population. The aim of this prospective study was to create templates depicting facial maturation in the younger age groups. Healthy Dutch volunteers were captured, without selection of inclusions. Three-dimensional average faces were created using MATLAB, for both genders in four age groups (4-8 years, 8-12 years, 12-16 years, and ≥16 years). Variation within the groups was calculated and depicted on an average face with a green to red colour scale, corresponding to standard deviations between 0 and ≥ 3 mm, respectively. Measurements of the distances of eight peri-oral landmarks were provided as ratios. The statistical analysis was performed using ANOVA and Tukey's test. Three-dimensional reconstructions of the average face and their first principal component were created for each gender and age group. The first principal component comprised the facial width for each group, and the variation of landmarks was low. All ratios showed an increasing trend with increasing age, except for the ratio of philtrum width to mouth width. This study is novel in comparing facial morphology by means of ratios and in creating average faces for the different young age groups. These data provide useful insights into facial maturation, which might be beneficial for facial surgeons.

Value of cone beam computed tomography for detecting bone invasion in squamous cell carcinoma of the maxilla.

OBJECTIVE: To determine the diagnostic value of cone beam computed tomography (CBCT) in detecting bone invasion in maxillary squamous cell carcinoma (MSCC). STUDY DESIGN: In this retrospective cohort study, preoperative CBCT scans were independently assessed by a single surgeon in imaging assessment 1 (IA 1) and by 1 surgeon with 2 dentists in consensus (IA 2) for the presence of bone invasion in MSCC. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, area under the receiver operating characteristic curve (AUC), and Cohen's κ were calculated. Histopathologic results of resection specimens served as the reference standard. RESULTS: Of 27 patients, 19 (70%) had proven bone invasion. IA 1 yielded 68.4% sensitivity, 75.0% specificity, 86.7% PPV, 50.0% NPV, 70.4% accuracy, and 0.717 AUC. All results of IA 2 were true-positive and true-negative, resulting in 100% sensitivity, specificity, PPV, NPV, accuracy, and AUC. The assessments differed in 6 cases. Interobserver κ was fair (0.38, 95% CI 0.04-0.72, P = .038). There was a significant association between CBCT detection of bone invasion and extent of surgical treatment (P = .006) CONCLUSIONS: The diagnostic accuracy of CBCT was high but observer-dependent. CBCT examination may be useful in surgical treatment planning.

Zygomaticomaxillary complex fracture repair with intraoperative CBCT imaging. A prospective cohort study.

The aim of this study was to evaluate the value of intraoperative conebeam computed tomography (CBCT) imaging in the treatment of zygomaticomaxillary complex (ZMC) fractures. A prospective single center cohort study was performed. Included were consecutive patients who underwent surgery for a unilateral ZMC fracture. An intraoperative CBCT scan was performed after reduction of the ZMC fracture. Revision reduction was performed of the ZMC and/or orbital floor (OF) on indication. The preoperative and postoperative asymmetry of the outer surface of the ZMC was measured on digital 3D-models of CBCT scans, using a mirroring and surface-based matching technique. The postoperative asymmetry of the ZMC in the study group was compared to the asymmetry of the ZMC in the control group with healthy individuals. A total of 38 patients with a unilateral ZMC fracture were included. The mean postoperative asymmetry in the study group (1.67 mm, SD 0.89) was less than the mean preoperative asymmetry (2.69 mm, SD 0.95) (paired samples T-test p < 0.01) but showed no statistically significant difference with the mean asymmetry in the healthy control group (1.40 mm, SD 0.54) (independent samples T-test p = 0.31). Revision reduction of the ZMC and/or OF fracture had been performed in 11 cases after malalignment was noted on the intraoperative CBCT. The indication for intraoperative revision reduction was associated with comminuted ZMC fractures and/or fractures with indication for OF reduction (Pearson Chi Square p < 0.01). Within the limitations of the study, intraoperative CBCT imaging seemed to have a positive influence on ZMC fracture treatment, especially in the case of comminuted ZMC fractures and/or fractures with indication for OF treatment.

Observing stage-shifts in head and neck squamous cell carcinoma from initial clinical outpatient staging to definite clinical tumour board staging using radiological and endoscopical investigations: will less do?

OBJECTIVES: Staging head and neck squamous cell carcinoma usually is initiated in the outpatient department (OPD) using patient history and physical examination. To reach consensus on stage and therapy, imaging and panendoscopy are more or less routinely applied as additional staging tests. Staging results from the outpatient department were evaluated for tumour and neck stage. We investigated in which situations additional staging tests are needed. DESIGN: Prospective cohort study. SETTING: Head and Neck Oncology Group, University Medical Centre. PARTICIPANTS: Of 341 patients, initial staging results from the outpatient department were compared with the ultimate staging results from the tumour board review, which provides the basis for decisions on therapy. MAIN OUTCOME MEASURES: Tumour stage and neck stage migrations during this staging tract. RESULTS: In staging head and neck tumours are squamous cell carcinomas, additional staging tests like imaging and/or panendoscopy remain necessary to evaluate the primary tumour stage. Average accuracies of T-staging in oral cavity, pharynx and larynx only amount to 71%, 47% and 61%, respectively. For T1N0 and T2N0 oral cavity tumours, neck assessment in the outpatient department was accurate in 100% (95% CI: 91-100%) and 93% (95% CI: 80-98%), respectively. In the larynx group, this was 100% (95% CI: 91-100%) and 97% (95% CI: 86-100%), respectively. CONCLUSIONS: For oral cavity and laryngeal tumours staged as T1-2N0 in the outpatient department, we concluded that the outpatient department staging is highly predictive of the final pre-treatment staging. In these cases, computer tomography and/or MRI remain a necessity but additional ultrasound with or without fine needle aspiration cytology can be omitted. In our institution, this would have resulted in a 46% reduction in ultrasound procedures. If T-stage is upgraded during imaging or panendoscopy, additional staging tests for N-stage should still be considered.

Inflammatory pseudotumour of the alveolar process of the maxilla as clinical manifestation of IgG4-related disease: a case report and literature review.

IgG4-related disease (IgG4-RD) is an uncommon immune-mediated condition considered to be a systemic disease, described in multiple organ systems. IgG4-RD that involves the maxillary and sinonasal region is rare. This report presents a very rare presentation of IgG4-RD in the maxillary alveolar process. The patient presented with left-sided facial pain, headache, and mobility and loss of teeth. The first biopsy and resection specimen reports were inconclusive and showed a non-specific chronic inflammatory process. After the third resection, the diagnosis was finally established through findings that satisfied the 2012 consensus criteria for IgG4-RD. Consequently high doses of oral corticosteroids and azathioprine were given, tapered over a total period of 36 months. Weaning is still in progress, but no recurrence was observed after 34 months. A review of the English-language literature was performed, which identified seven cases of IgG4-RD with maxillary and sinonasal involvement. Cases were excluded from the review if there was any doubt that they met the consensus statement on the pathology.

Endochondral Bone Regeneration by Non-autologous Mesenchymal Stem Cells.

Mimicking endochondral bone formation is a promising strategy for bone regeneration. To become a successful therapy, the cell source is a crucial translational aspect. Typically, autologous cells are used. The use of non-autologous mesenchymal stromal cells (MSCs) represents an interesting alternative. Nevertheless, non-autologous, differentiated MSCs may trigger an undesired immune response, hampering bone regeneration. The aim of this study was to unravel the influence of the immune response on endochondral bone regeneration, when using xenogeneic (human) or allogeneic (Dark Agouti) MSCs. To this end, chondrogenically differentiated MSCs embedded in a collagen carrier were implanted in critical size femoral defects of immunocompetent Brown Norway rats. Control groups were included with syngeneic/autologous (Brown Norway) MSCs or a cell-free carrier. The amount of neo-bone formation was proportional to the degree of host-donor relatedness, as no full bridging of the defect was observed in the xenogeneic group whereas 2/8 and 7/7 bridges occurred in the allogeneic and the syngeneic group, respectively. One week post-implantation, the xenogeneic grafts were invaded by pro-inflammatory macrophages, T lymphocytes, which persisted after 12 weeks, and anti-human antibodies were developed. The immune response toward the allogeneic graft was comparable to the one evoked by the syngeneic implants, aside from an increased production of alloantibodies, which might be responsible for the more heterogeneous bone formation. Our results demonstrate for the first time the feasibility of using non-autologous MSC-derived chondrocytes to elicit endochondral bone regeneration in vivo. Nevertheless, the pronounced immune response and the limited bone formation observed in the xenogeneic group undermine the clinical relevance of this group. On the contrary, although further research on how to achieve robust bone formation with allogeneic cells is needed, they may represent an alternative to autologous transplantation.

Low skeletal muscle mass is a strong predictive factor for surgical complications and a prognostic factor in oral cancer patients undergoing mandibular reconstruction with a free fibula flap.

BACKGROUND: Fibula free flaps (FFF) are effective in accomplishing successful reconstruction for segmental defects of the mandible. Potential risk factors for FFF complications have been described in previous research, e.g. age, comorbidity and smoking. Low skeletal muscle mass (SMM) has shown to be an emerging predictive factor for complications and prognostic factor for survival in head and neck cancer. This study aims to identify the predictive and prognostic value of low SMM for surgical FFF related complications, postoperative complications and survival in patients who underwent mandibular reconstruction with FFF after oral cavity cancer resection. MATERIALS AND METHODS: A retrospective study was performed between 2002 and 2018. Pre-treatment SMM was measured at the level of the third cervical vertebra and converted to SMM at the level of the third lumbar vertebra (L3). SMM at the level of L3 was corrected for squared height. Low SMM was defined as a lumbar skeletal muscle index (LSMI) below 43.2 cm2/m2. RESULTS: 78 patients were included, of which 48 (61.5%) had low SMM. Low SMM was associated with an increased risk of FFF related complications (HR 4.3; p = 0.02) and severe postoperative complications (Clavien-Dindo grade III-IV) (HR 4.0; p = 0.02). In addition low SMM was a prognosticator for overall survival (HR 2.4; p = 0.02) independent of age at time of operation, ACE-27 score and TNM stage. CONCLUSION: Low SMM is a strong predictive factor for FFF reconstruction complications and other postoperative complications in patients undergoing FFF reconstruction of the mandible. Low SMM is also prognostic for decreased overall survival.

Feasibility of CT quantification of intratumoural 166Ho-microspheres.

BACKGROUND: Microspheres loaded with radioactive 166Ho (166Ho-MS) are novel particles for radioembolisation and intratumoural treatment. Because of the limited penetration of ß radiation, quantitative imaging of microsphere distribution is crucial for optimal intratumoural treatment. Computed tomography (CT) may provide high-resolution and fast imaging of the distribution of these microspheres, with lower costs and widespread availability in comparison with current standard single-photon emission tomography (SPECT) and magnetic resonance imaging. This phantom study investigated the feasibility of CT quantification of 166Ho-MS. METHODS: CT quantification was performed on a phantom with various concentrations of HoCl and Ho-MS to investigate the CT sensitivity and calibrate the CT recovery. 166Ho-MS were injected into ex vivo tissues, in VX-2 cancer-bearing rabbits, and in patients with head-neck cancer, to demonstrate sensitivity and clinical visibility. The amount of Ho-MS was determined by CT scanning, using a density-based threshold method and compared with a validated 166Ho SPECT quantification method. RESULTS: In the phantom, a near perfect linearity (least squares R2 > 0.99) between HU values and concentration of 166Ho was found. Ex vivo tissue experiments showed an excellent correlation (r = 0.99, p < 0.01) between the dose calibrator, SPECT, and CT imaging. CT recovery was on average 86.4% ex vivo, 76.0% in rabbits, and 99.1% in humans. CONCLUSION: This study showed that CT-based quantification of Ho microspheres is feasible and is a high-resolution alternative to SPECT-based determination of their local distribution.

Articular soft tissue injuries associated with mandibular condyle fractures and the effects on oral function.

The majority of studies debating the optimization of treatment for condylar mandibular fractures focus on the bony aspect first. However, fractures of the mandibular condyle may go together with soft tissue injury of the temporomandibular joint. An electronic literature search for this topic was undertaken. Assessment of quality was carried out using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Sixteen articles were included in this review. The reviewed literature showed that intracapsular fractures and dislocated condylar fractures result in more severe injuries. Serious injury to the disc and capsule of the temporomandibular joint is a contributing factor towards development of complications after closed treatment. The results of this review give an overview of the published studies focusing on articular soft tissue injuries caused by condylar mandibular fractures. Additionally, an overview of the magnetic resonance imaging (MRI) settings used to detect these injuries is provided. Until now, the relation between soft tissue injuries and type of condylar trauma and their influence on clinical outcome has been insufficiently investigated. Before considering reduction of soft tissues next to reduction of the fracture, more research is needed into the impact of soft tissue injuries on oral functioning, in which a uniform classification is used.

Intact vitreous humor as a potential extracellular matrix hydrogel for cartilage tissue engineering applications.

Decellularisation of tissues, utilising their biochemical cues, poses exciting tissue engineering (TE) opportunities. However, removing DNA from cartilage (dCart) requires harsh treatments due to its dense structure, causing loss of bioactivity and limiting its application as a cartilaginous extra cellular matrix (ECM). In this study, we demonstrate for the first time the successful application of vitreous humor (VH), a highly hydrated tissue closely resembling the glycosaminoglycan (GAG) and collagen composition of cartilage, as an ECM hydrogel to support chondrogenic differentiation. Equine VH was extracted followed by biochemical quantifications, histological examinations, cytotoxicity (human mesenchymal stromal cells, hMSCs and human articular chondrocytes, hACs) and U937 cell proliferation studies. VH was further seeded with hACs or hMSCs and cultured for 3-weeks to study chondrogenesis compared to scaffold-free micro-tissue pellet cultures and collagen-I hydrogels. Viability, metabolic activity, GAG and DNA content, chondrogenic gene expression (aggrecan, collagen I/II mRNA) and mechanical properties were quantified and matrix deposition was visualised using immunohistochemistry (Safranin-O, collagen I/II). VH was successfully extracted, exhibiting negligible amounts of DNA (0.4 ±â€¯0.4 µg/mg dry-weight) and notable preservation of ECM components. VH displayed neither cytotoxic responses nor proliferation of macrophage-like U937 cells, instead enhancing both hMSC and hAC proliferation. Interestingly, encapsulated cells self-assembled the VH-hydrogel into spheroids, resulting in uniform distribution of both GAGs and collagen type II with increased compressive mechanical properties, rendering VH a permissive native ECM source to fabricate cartilaginous hydrogels for potential TE applications. STATEMENT OF SIGNIFICANCE: Fabricating bioactive and cell-instructive cartilage extracellular matrix (ECM) derived biomaterials and hydrogels has over recent years proven to be a challenging task, often limited by poor retention of inherent environmental cues post decellularisation due to the dense and avascular nature of native cartilage. In this study, we present an alternative route to fabricate highly permissive and bioactive ECM hydrogels from vitreous humor (VH) tissue. This paper specifically reports the discovery of optimal VH extraction protocols and cell seeding strategy enabling fabrication of cartilaginous matrix components into a hydrogel support material for promoting chondrogenic differentiation. The work showcases a naturally intact and unmodified hydrogel design that improves cellular responses and may help guide the development of cell instructive and stimuli responsive hybrid biomaterials in a number of TERM applications.