Calcified Cartilage Research Articles

Premature Calcification of Costochondral Cartilage: A Scoping Review of the Literature

Premature Calcification of Costochondral Cartilage: A Scoping Review of the Literature

Comparison of Early-Stage Knee Osteoarthritis Induced by Medial Meniscus Tear Versus Tibial Osteotomy in the Rat Model.

Medial meniscus tear (MMT) is a common method to induce osteoarthritis in rats, but mimics secondary osteoarthritis. A novel method of carrying out a medial wedge closing tibial osteotomy (TO) has been recently developed to induce primary osteoarthritis. This study aims to validate it, compared to MMT. Twenty rats were divided equally into 2 groups. Outcome measures such as histology graded according to Osteoarthritis Research Society International (OARSI) guidelines and computed tomography (CT) scans were analyzed at 6 weeks post-operatively. Observational gait analysis and serum biomarkers such as C-terminal cross-linked telopeptides of type II collagen (CTX-II) and interleukin-1 beta (IL-1β) were collected at 2-weekly intervals up to 6 weeks post-operatively. Serum CTX-II and IL-1β levels did not reveal a statistically significant difference across all time points between the 2 groups. CT grading was significantly more severe (2.80 ± 1.10 vs 1.40 ± 0.548, P = 0.0389) in the MMT group compared to the TO group. In addition, histological gradings such as calcified cartilage score (2.10 ± 1.91 vs 0.00 ± 0.00, P < 0.01) and cartilage degeneration score (4.80 ± 5.18 vs 0.00 ± 0.00, P < 0.01) revealed significantly more severe osteoarthritis in the MMT compared to TO group. Synovial membrane score did not reveal a statistically significant difference (1.10 ± 0.994 vs 1.00 ± 0.00, P = 1.00). TO is a novel method in inducing primary osteoarthritis in the rat model compared to MMT between the 6 and 12 weeks' time frame.

Bending properties of human cartilaginous ribs and costal cartilage material vary with age, sex, and calcification.

Costal cartilage plays an important functional role in the rib cage, but its mechanical properties have not been well characterized. The objective of this study is to characterize the properties of human costal cartilage and examine the effects of age, sex, rib level, and degree of calcification. We obtained cadaveric costal cartilage samples of ribs 3-6 with intact perichondrium from 24 donors (12 females and 12 males) evenly distributed by age (range 47-94yr). Peripheral QCT scans were used to quantify geometric properties (area moments) and tissue calcification (as volume, length, and classified as central, peripheral, and mixed). Four-point bending tests were performed on each sample, and bending stiffness and modulus outcomes were evaluated by fitting data from mechanical testing with non-linear pseudo-elastic models (composed of linear and cubic components, separated into loading and unloading regimes). Effects of sex, age, rib level, and cartilage calcification on bending stiffness and modulus outcomes were assessed with mixed-effects regression models. Cartilage size (area moment) was larger in males than females and positively associated with age, while there was more calcification volume in cartilage of females than males. During loading, stiffness (linear and cubic) was larger in males, while modulus (linear and cubic) was larger in females. Linear stiffness and modulus were both negatively associated with age, positively associated with calcification, and varied between rib levels. Cubic (nonlinear) components of stiffness and modulus were positively associated with calcification and varied by rib, while modulus (but not stiffness) was negatively associated with age. During unloading, the linear stiffness and modulus values were much lower, though some similar associations were found. Overall, this study adds to our understanding of the behavior of costal cartilage as a nonlinear visco-elastic material, and the effects of sex, aging, and calcification on mechanical behavior.

Designing biphasic nanocellulose hydrogels to mimic the complex cartilage-bone interface

Osteochondral lesions, which affect both the cartilage and the bone, present significant challenges in treatment due to the complex mechanical and biochemical properties of these tissues. A crucial consideration in developing tissue replacements for these lesions is the simultaneous regeneration of cartilage and calcified cartilage, which forms the transition zone to bone. Our current study aims to fabricate a bilayer polymeric hydrogel designed not only to support cartilage regeneration but also to serve as an interface between cartilage and bone. The bilayer hydrogel was created by combining oxidized bacterial nanocellulose, gelatin, and alginate in one layer, while the other layer consisted of the same three biopolymers and hydroxyapatite. The bacterial nanocellulose was effectively oxidized (20%) with sodium periodate and then mineralized with calcium and phosphorus (Ca/P ratio = 0.97), as confirmed by EDX analysis. Remarkably, both layers of the biphasic hydrogel demonstrated cytocompatibility with chondrocytes. Moreover, the addition of hydroxyapatite significantly improved the mechanical strength from 72 kPa (OBC/Gel/Alg) to 90 kPa (MOBC/Gel/Alg). This bilayer hydrogel holds promise for promoting bone-cartilage integration and has the potential to contribute to the healing of osteochondral defects, offering new possibilities in the field of orthopedic tissue engineering and regenerative medicine.

RNA sequencing uncovers key players of cartilage calcification: potential implications for osteoarthritis pathogenesis.

Osteoarthritis (OA) is a joint disease linked with pathologic cartilage calcification, caused by the deposition of calcium-containing crystals by chondrocytes. Despite its clinical significance, the precise mechanisms driving calcification remain elusive. This study aimed to identify crucial players in cartilage calcification, offering insights for future targeted interventions against OA. Primary murine chondrocytes were stimulated with secondary calciprotein particles (CPP2) or left untreated (NT) for 6 h. Calcification was assessed by alizarin red staining. RNA was analyzed by Bulk RNA sequencing. Differentially expressed (DE) genes were identified (cutoff: abs(LogFC)>1 and adj.p-val < 0.05), and top 50 DE genes were cross-referenced with human OA datasets from previous studies (ie healthy vs OA cartilage, or undamaged vs damaged cartilage). RNA from NT and CPP2-stimulated primary human OA chondrocytes were used to validate genes by qPCR. CPP2 induced crystal formation by chondrocytes and significantly modulated 1466 genes. Out of the top 50 DE genes in CPP2, 27 were confirmed in published OA cartilage datasets. Of those genes, some are described in calcification and/or OA (Errfi1, Ngf, Inhba, Col9a1). Two additional ones (Rcan1, Tnfrsf12a) appear novel and interesting in the context of calcification and OA. We validated modulation of these six genes in calcifying human chondrocytes from 5 patients. Ultimately, we unveiled two distinct gene families modulated by CPP2: the first comprised cytoskeletal genes (Actb, Tpm1, Cfl1, Tagln2, Lmna), while the second encompassed extracellular matrix genes (Fmod, Sparc, Col9a1, Cnmd). CPP2 modulates genes in chondrocytes that could represent new targets for therapeutic interventions in OA.

Bone microstructure analyses in ontogenetic series of Mesosaurus tenuidens from the early Permian of Brazil.

Osteohistological evidence is widely used to infer paleobiological traits of fossil vertebrates, such as ontogeny and growth rates. Mesosaurs, an enigmatic group of aquatic reptiles from the early Permian, are the most well-known Paleozoic amniotes from Africa and South America. Their fossils are abundant in South America, ranging from the central-west region of Brazil to the southernmost areas, as well as parts of Paraguay and Uruguay. In this contribution, we examined the bone microstructure of Mesosaurus tenuidens by analyzing thin sections of axial and appendicular elements of several specimens collected from various Brazilian sites. The microstructure of the bones showed minimal histological variability among elements, predominantly composed of parallel-fibered tissues, indicating slow growth rhythm, along with increased bone density attributed to pachyosteosclerosis. The cortical area consists of poorly vascularized parallel-fibered bone tissue, which was interrupted by multiple cyclical growth marks, some of them being supernumerary, suggesting a strong influence of seasonality. Moreover, the organization of growth marks suggests distinct life history trajectories among individuals collected from different outcrops, reflecting environmental heterogeneity throughout the basin. Internally, the endosteal domain exhibits greater vascularization compared to the cortices and frequently contained calcified cartilage. In the ontogenetic series, there was a progressive filling of the medullary region from small to large individuals. The presence of the External Fundamental System (a proxy indicating somatic maturity) was observed in femora and ribs, suggesting that determinate growth was already occurring in Permian mesosaurs and may not be an exclusive specialization of crown amniotes.

Unique bone histology of modern giant salamanders: a study on humeri and femora of Andrias spp.

The osteohistology of Andrias spp. is a pivotal analogue for large fossil non-amniotes (e.g., Temnospondyli), and the endangered status of this taxon underlines the importance of gathering information on its growth. We here present the first osteohistological study by petrographic thin sections of an ontogenetic series of humeri and femora of eight individuals of varying sizes (28.5–104 cm) and ages (2.5–32 years) of Andrias japonicus from the Hiroshima City Asa Zoological Park, Japan. In addition, two individuals of A. cf. davidianus of unknown age but of different size (62 cm and 94 cm) were studied. All samples of Andrias spp. show a primary avascular periosteal cortex made of parallel-fibred tissue around the ossification center in the petrographic thin sections. Mainly in small individuals, the fibers forming this tissue are very coarse and loosely organized. With increasing size and age, the coarse tissue is irregularly intermixed and later replaced with finer and better organized fibers. This histologic change is accompanied by a change from diffuse annuli in the inner cortex to distinct lines of arrested growth (LAGs) in the outer cortex. We interpret these changes in tissue and the appearance of distinct growth marks as indicating the onset of active reproduction. The lack of primary vascularization around the ossification center in our Andrias spp. sample is striking and contradicts other observations. Vascularity may be prone to plasticity and further studies are necessary. We hypothesize that the large osteocyte lacunae and the dense networks of canaliculi observed in our sample may have nourished the tissue instead of primary vascular canals. We measured the size of osteocyte lacunae of Andrias spp. in comparison to other Lissamphibia, and found them to be significantly larger throughout ontogeny. The periosteal cortex contains a high amount of thick Sharpey’s fibers all around the midshaft cross sections. The two samples of Andrias cf. davidianus show tissue and growth mark distribution similar to that observed in A. japonicus. However, the large individual of A. cf. davidianus differed in its extremely osteosclerotic condition and the retention of a small layer of calcified cartilage in the endosteal region of the femur. It remains unclear whether these differences are related to plasticity, taxonomy, sex, exogenous factors, or attributable to a regenerated but fully regrown leg. Although the present study is based on zoo-kept and not wild, animals, it yields important insights into osteohistological plasticity and growth patterns in giant salamanders.

Injectable Janus Base Nanomatrix (JBNm) in Maintaining Long-Term Homeostasis of Regenerated Cartilage for Tissue Chip Applications.

Engineered cartilage tissues have wide applications in in vivo cartilage repair as well as in vitro models, such as cartilage-on-a-chip or cartilage tissue chips. Currently, most cartilage tissue engineering approaches focus on promoting chondrogenesis of stem cells to produce regenerated cartilage. However, this regenerated cartilage can dedifferentiate into fibrotic tissue or further differentiate into hypertrophic or calcified cartilage. One of the most challenging objectives in cartilage tissue engineering is to maintain long-term cartilage homeostasis. Since the microenvironment of engineered cartilage tissue is crucial for stem cell adhesion, proliferation, differentiation, and function, we aim to develop a novel scaffold that can maintain the long-term homeostasis of regenerated cartilage. Therefore, we developed a library of Janus base nanomatrices (JBNms), composed of DNA-inspired Janus nanotubes (JBNts) as well as cartilage extracellular matrix (ECM) proteins. The JBNms were developed to selectively promote chondro-lineage cell functions while inhibiting bone and endothelial cell growth. More importantly, the JBNm can effectively promote chondrogenesis while inhibiting hypertrophy, osteogenesis, angiogenesis, and dedifferentiation. Additionally, the JBNm is injectable, forming a solid scaffold suitable for producing and maintaining regenerated cartilage tissue in microfluidic chips, making it ideal for tissue chip applications. In this study, we successfully created cartilage tissue chips using JBNms. These chips can model cartilage tissue even after long-term culture and can also mimic arthritis progression, making them useful for drug screening. Thus, we have developed a novel nanomaterial approach for improved cartilage tissue engineering and cartilage tissue chip applications.

New role of calcium-binding fluorescent dye alizarin complexone in detecting permeability from articular cartilage to subchondral bone.

Osteoarthritis (OA) is a chronic degenerative joint disorder characterized by the progressive deterioration of articular cartilage and concomitant alterations in subchondral bone architecture. However, the precise mechanisms underlying the initiation and progression of OA remains poorly understood. In the present study, we explored whether the calcification in the articular cartilage occurred in the early stage of mouse OA model, generated by the surgery destabilization of the medial meniscus (DMM), via the intra-articular injection of alizarin complexone due to its anionic nature for binding calcium-containing crystals. Although we did not observe the calcification in the articular cartilage of early stage of DMM mice, we unexpectedly identified alizarin complexone had the diffusion capacity for detecting the permeability from the articular cartilage to subchondral bone. Our data showed that the diffusion of alizarin complexone from the articular cartilage to calcified cartilage was greater in the early stage of DMM mice than that in sham controls. Additionally, we observed enhanced penetration of alizarin complexone through the periosteum in DMM mice compared to sham mice. In summary, we developed a novel imaging method that offers a valuable tool for further exploration of biochemical communication underlying OA development. Our findings provided new evidence that increased molecular interactions between the articular cartilage and subchondral bone is involved in the pathogenesis of OA progression.

Gelatin-based hydrogels with tunable network structure and mechanical property for promoting osteogenic differentiation

Osteoarthritis (OA) is a joint disease involving all joint components, including cartilage, calcified cartilage, and subchondral bone. The repair of osteochondral defects remains a significant challenge in orthopedics. Development of new strategies is essential for effective osteochondral injury repair. In this study, gelatin (Gel), polyethylene glycol diglycidyl ether (PEGDGE), hydroxyethyl cellulose (HEC) and chitosan (CS) were used to prepare semi-IPNs and IPNs hydrogels. Mechanical properties of Gel based hydrogels significantly improved with the semi-IPN and IPN structures. Tensile strength ranges from 238.7 KPa to 479.5 KPa, and its compressive strength ranges from 35.6 KPa to 112.7 KPa. Additionally, the stress relaxation rate increased with higher CS concentrations, ranging from 25 % to 35 %. The network structure of Gel-based hydrogels was a key factor in regulating stress relaxation. Viscoelasticity was adjusted by its network structures. Swelling and degradation behaviors of Gel based hydrogels were systematically investigated. Gel based hydrogels had good cytocompatibility. Both semi-IPN and IPN structures Gel based hydrogels could promote cell spreading and osteogenic differentiation. G10HEC1 and G10CS1 hydrogels show promise as candidates for osteochondral tissue regeneration, offering a new strategy for osteochondral tissue engineering.

The Significance of Intracellular Versus Extracellular Calcium Pyrophosphate Crystals in Diagnosing Calcium Pyrophosphate Crystal Arthritis.

Acute and chronic calcium pyrophosphate (CPP) crystal arthritis is characterized by the presence of synovial CPP crystals within a clinically inflamed joint. CPP crystals may be situated intracellularly or extracellularly; however, the clinical significance of their location remains understudied. The objective of this retrospective cohort study was to assess the relevance of the CPP crystal location in diagnosing acute/chronic CPP crystal arthritis. Data were collected from Waikato District Health Board to identify a study population with synovial fluid samples positive for CPP crystals. The cohort was stratified into 2 groups based on crystal location: intracellular and extracellular. The proportions of acute/chronic CPP crystal arthritis cases were compared between these groups. Acute/chronic CPP crystal arthritis was diagnosed when synovial CPP crystals were present, with objective evidence of joint inflammation and no other alternative diagnosis. Further analysis was made with respect to demographics, other laboratory results, and cartilage calcification. This study included 134 patients: 108 with intracellular CPP crystals and 26 with extracellular CPP crystals. Acute/chronic CPP crystal arthritis was diagnosed in 85% of cases in the intracellular and 50% in the extracellular group (P < 0.001). Following exclusion of septic arthritis cases, acute/chronic CPP crystal arthritis was diagnosed in 97% of patients in the intracellular group and in 62% of those in the extracellular group (P < 0.001). The presence of intracellular CPP crystals is more strongly associated with acute/chronic CPP crystal arthritis than with extracellular CPP crystals alone.

Instrumentation Considerations for Calcified Thyroid Cartilage during Chondrolaryngoplasty

ObjectiveChondrolaryngoplasty, also known as thyroid cartilage reduction, alleviates gender dysphoria by reducing the thyroid cartilage to conform to a patient's gender identity. Reduction of the thyroid cartilage prominence (“Adam's apple”) is often performed with a scalpel, but in cases of cartilage calcification, rongeurs or drills are utilized. This study aims to characterize the success rate with scalpel‐only excision and relate this to patient age and operative time.MethodsBilling records were screened for chondrolaryngoplasties performed between 2020 and 2023 by a single surgeon. Patient demographics, operative notes, and operation duration were recorded. Type of instrumentation was categorized as scalpel only, rongeur, or drill. All cases began with attempted scalpel excision of cartilage and were transitioned to rongeur or drill if there was calcification that prevented sharp excision. Descriptive statistics were used to describe patient and surgical factors.Results52 individuals underwent chondrolaryngoplasty: 30 cases (57.7%) had soft cartilage requiring only a blade, 22 (42.3%) required use of either drill or rongeur. The average age of these groups was 25.7 (SE 1.8) and 41.3 years (SE 2.2), respectively; this difference was statistically significant (p &lt; 0.0001). Cases requiring a drill or rongeur lasted on average 78.5 min (SE 2.3), whereas those using only a blade were shorter at 66.8 min (SE 2.7); this difference was significant (p = 0.0017).ConclusionCartilage calcification should be expected in a significant number of chondrolaryngoplasties, and surgeons should be prepared for this scenario. The need for alternative instrumentation is higher in older individuals and may extend procedural time.Level of Evidence4 Laryngoscope, 2024

The diagnostic utility of CT attenuation values in detecting calcification within costal cartilage

BackgroundTo establish and verify diagnostic criteria for the identification of costal cartilage calcification based on CT attenuation value. Methods360 chest CT slices of 120 patients were reviewed and annotated retrospectively and ROC curve was used to evaluate the diagnostic ability of CT attenuation value. Another 20 slices containing calcification were randomly selected and annotated by 4 doctors for further validation. H&E and COLX staining was performed on the residual costal cartilage. ResultsIn total 355129 voxels were detected and 187.5 was confirmed as the optimal CT attenuation value threshold, with a sensitivity of 98.6% and a specificity of 99.7%, for costal cartilage calcification diagnosis. Threshold-based identification of calcification demonstrated a similarity of nearly 80% with specialists' assessments, and exhibited advantages in the identification of subtle calcifications in the further validation. We also observed that CT attenuation values among males demonstrated a centralized distribution, whereas those among females exhibited a bimodal distribution. Threshold-based identified calcification showed a positivity of COLX. ConclusionsCT attenuation value could validly and reliably diagnose calcification within costal cartilage. Further investigations involving larger cohorts of patients are required to elucidate the risk factors and underlying mechanisms of costal cartilage calcification.

Comparative Morphology of Skeletal Development in Homo sapiens and Raja asterias: Divergent Stiffening Patterns Due to Different Matrix Calcification Processes.

Before calcification begins, the early embryonic and fetal skeletal development of both mammalian Homo sapiens and the chondrichthyan fish Raja asterias consists exclusively of cartilage. This cartilage is formed and shaped through processes involving tissue segmentation and the frequency, distribution, and orientation of chondrocyte mitoses. In the subsequent developmental phase, mineral deposition in the cartilage matrix conditions the development further. The stiffness and structural layout of the mineralized cartilage have a significant impact on the shape of the anlagen (early formative structure of a tissue, a scaffold on which the new bone is formed) and the mechanical properties of the skeletal segments. The fundamental difference between the two studied species lies in how calcified cartilage serves as a scaffold for osteoblasts to deposit bone matrix, which is then remodeled. In contrast, chondrichthyans retain the calcified cartilage as the definitive skeletal structure. This study documents the distinct mineral deposition pattern in the cartilage of the chondrichthyan R. asterias, in which calcification progresses with the formation of focal calcification nuclei or "tesserae". These are arranged on the flat surface of the endo-skeleton (crustal pattern) or aligned in columns (catenated pattern) in the radials of the appendicular skeleton. This anatomical structure is well adapted to meet the mechanical requirements of locomotion in the water column. Conversely, in terrestrial mammals, endochondral ossification (associated with the remodeling of the calcified matrix) provides limb bones with the necessary stiffness to withstand the strong bending and twisting stresses of terrestrial locomotion. In this study, radiographs of marine mammals (reproduced from previously published studies) document how the endochondral ossification in dolphin flippers adapts to the mechanical demands of aquatic locomotion. This adaptation includes the reduction in the length of the stylopodium and zeugopodium and an increase in the number of elements in the autopodium's central rays.

3D-printed gradient scaffolds for osteochondral defects: Current status and perspectives.

Articular osteochondral defects are quite common in clinical practice, and tissue engineering techniques can offer a promising therapeutic option to address this issue.The articular osteochondral unit comprises hyaline cartilage, calcified cartilage zone (CCZ), and subchondral bone.As the interface layer of articular cartilage and bone, the CCZ plays an essentialpart in stress transmission and microenvironmental regulation.Osteochondral scaffolds with the interface structure for defect repair are the future direction of tissue engineering. Three-dimensional (3D) printing has the advantages of speed, precision, and personalized customization, which can satisfy the requirements of irregular geometry, differentiated composition, and multilayered structure of articular osteochondral scaffolds with boundary layer structure. This paper summarizes the anatomy, physiology, pathology, and restoration mechanisms of the articular osteochondral unit, and reviews the necessity for a boundary layer structure in osteochondral tissue engineering scaffolds and the strategy for constructing the scaffolds using 3D printing. In the future, we should not only strengthen the basic research on osteochondral structural units, but also actively explore the application of 3D printing technology in osteochondral tissue engineering. This will enable better functional and structural bionics of the scaffold, which ultimately improve the repair of osteochondral defects caused by various diseases.

Change in Thickness of Adult Male Human Calcified Articular Cartilage Zone with Aging

Objective: To measure change in the thickness of calcified cartilage zone of male human articular cartilage (AC). Methodology: Forty articular cartilage samples. were collected from the right knees of male cadavers aged between 21 to 60 years. The samples were placed in four groups. Tissue processing and cutting were followed by H&amp;E staining. And calcified cartilage zone thickness was measured. Results: With advancing age there was increase in thickness of articular cartilage at knee joint. Conclusions: With advancing age, the calcified articular cartilage zone thickness increases leading to osteoarthritis. Delaying or preventing of this change with aging makes this zone an important target for preventive and therapeutic measures.

Materials Suitable for Osteochondral Regeneration.

Osteochondral defects affect articular cartilage, calcified cartilage, and subchondral bone. The main problem that they cause is a different behavior of cell tissue in the osteochondral and bone part. Articular cartilage is composed mainly of collagen II, glycosaminoglycan (GAG), and water, and has a low healing ability due to a lack of vascularization. However, bone tissue is composed of collagen I, proteoglycans, and inorganic composites such as hydroxyapatite. Due to the discrepancy between the characters of these two parts, it is difficult to find materials that will meet all the structural and other requirements for effective regeneration. When designing a scaffold for an osteochondral defect, a variety of materials are available, e.g., polymers (synthetic and natural), inorganic particles, and extracellular matrix (ECM) components. All of them require the accurate characterization of the prepared materials and a number of in vitro and in vivo tests before they are applied to patients. Taken in concert, the final material needs to mimic the structural, morphological, chemical, and cellular demands of the native tissue. In this review, we present an overview of the structure and composition of the osteochondral part, especially synthetic materials with additives appropriate for healing osteochondral defects. Finally, we summarize in vitro and in vivo methods suitable for evaluating materials for restoring osteochondral defects.

Histological and Histopathological Features of the Third Metacarpal/Tarsal Parasagittal Groove and Proximal Phalanx Sagittal Groove in Thoroughbred Horses with Racing History.

Information regarding the histopathology of the proximal phalanx (P1) sagittal groove in racehorses is limited. Twenty-nine cadaver limbs from nine Thoroughbred racehorses in racing/race-training underwent histological examination. Histological specimens of the third metacarpal/metatarsal (MC3/MT3) parasagittal grooves and P1 sagittal grooves were graded for histopathological findings in hyaline cartilage (HC), calcified cartilage (CC), and subchondral plate and trabecular bone (SCB/TB) regions. Histopathological grades were compared between (1) fissure and non-fissure locations observed in a previous study and (2) dorsal, middle, and palmar/plantar aspects. (1) HC, CC, and SCB/TB grades were more severe in fissure than non-fissure locations in the MC3/MT3 parasagittal groove (p < 0.001). SCB/TB grades were more severe in fissure than non-fissure locations in the P1 sagittal groove (p < 0.001). (2) HC, CC, and SCB/TB grades including SCB collapse were more severe in the palmar/plantar than the middle aspect of the MC3/MT3 parasagittal groove (p < 0.001). SCB/TB grades including SCB collapse were more severe in the dorsal and middle than the palmar/plantar aspect of the P1 sagittal groove (p < 0.001). Histopathology in the SCB/TB region including bone fatigue injury was related to fissure locations, the palmar/plantar MC3/MT3 parasagittal groove, and the dorsal P1 sagittal groove.

Unveiling the role of hypertrophic chondrocytes in abnormal cartilage calcification: insights into osteoarthritis mechanisms

Unveiling the role of hypertrophic chondrocytes in abnormal cartilage calcification: insights into osteoarthritis mechanisms

Bioceramic-mediated chondrocyte hypertrophy promotes calcified cartilage formation for rabbit osteochondral defect repair

Osteochondral tissue is a highly specialized and complex tissue composed of articular cartilage and subchondral bone that are separated by a calcified cartilage interface. Multilayered or gradient scaffolds, often in conjunction with stem cells and growth factors, have been developed to mimic the respective layers for osteochondral defect repair. In this study, we designed a hyaline cartilage-hypertrophic cartilage bilayer graft (RGD/RGDW) with chondrocytes. Previously, we demonstrated that RGD peptide-modified chondroitin sulfate cryogel (RGD group) is chondro-conductive and capable of hyaline cartilage formation. Here, we incorporated whitlockite (WH), a Mg2+-containing calcium phosphate, into RGD cryogel (RGDW group) to induce chondrocyte hypertrophy and form collagen X-rich hypertrophic cartilage. This is the first study to use WH to produce hypertrophic cartilage. Chondrocytes-laden RGDW cryogel exhibited significantly upregulated expression of hypertrophy markers in vitro and formed ectopic hypertrophic cartilage in vivo, which mineralized into calcified cartilage in bone microenvironment. Subsequently, RGD cryogel and RGDW cryogel were combined into bilayer (RGD/RGDW group) and implanted into rabbit osteochondral defect, where RGD layer supports hyaline cartilage regeneration and bioceramic-containing RGDW layer promotes calcified cartilage formation. While the RGD group (monolayer) formed hyaline-like neotissue that extends into the subchondral bone, the RGD/RGDW group (bilayer) regenerated hyaline cartilage tissue confined to its respective layer and promoted osseointegration for integrative defect repair.