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BACKGROUND: In the initial stage of growth plate injury inflammation, platelet-derived growth factor BB promotes the repair of growth plate injury by promoting mesenchymal progenitor cell infiltration, chondrogenesis, osteogenic response, and regulating bone remodeling. OBJECTIVE: To elucidate the action mechanism of platelet-derived growth factor BB after growth plate injury METHODS: PubMed, VIP, WanFang, and CNKI databases were used as the literature sources. The search terms were “growth plate injury, bone bridge, platelet-derived growth factor BB, repair” in English and Chinese. Finally, 66 articles were screened for this review. RESULTS AND CONCLUSION: Growth plate injury experienced early inflammation, vascular reconstruction, fibro ossification, structural remodeling and other pathological processes, accompanied by the crosstalk of chondrocytes, vascular endothelial cells, stem cells, osteoblasts, osteoclasts and other cells. Platelet-derived growth factor BB, as an important factor in the early inflammatory response of injury, regulates the injury repair process by mediating a variety of cellular inflammatory responses. Targeting the inflammatory stimulation mediated by platelet-derived growth factor BB may delay the bone bridge formation process by improving the functional activities of osteoclasts, osteoblasts, and chondrocytes, so as to achieve the injury repair of growth plate. Platelet-derived growth factor BB plays an important role in angiogenesis and bone repair tissue formation at the injured site of growth plate and intrachondral bone lengthening function of uninjured growth plate. Inhibition of the coupling effect between angiogenesis initiated by platelet-derived growth factor BB and intrachondral bone formation may achieve the repair of growth plate injury. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tissue engineering is considered an ideal treatment for growth plate regeneration. However, most of the current research on regenerative tissue engineering is the traditional scaffold-based strategy. As the limitations of traditional scaffolds are gradually revealed, the research direction is gradually diversifying. OBJECTIVE: To summarize the application of scaffold-based and scaffold-free strategies in the treatment of growth plate cartilage regeneration and their respective advantages and disadvantages. METHODS: The relevant articles were searched from PubMed, Wiley, and Elsevier. The search terms were “growth plate injury, regeneration, tissue engineering, scaffold, scaffold-free, biomimetic, cartilage” in English. The time was limited from 1990 to 2023. Finally, 104 articles were included for review. RESULTS AND CONCLUSION: The biomimetic strategy is to reduce the cell composition, biological signals and unique mechanical properties of each region to the greatest extent by simulating the unique organizational structure of the growth plate, so as to build a biomimetic microenvironment that can promote tissue regeneration. Therefore, the design of a biomimetic scaffold is to simulate the original growth plate as far as possible in terms of composition, structure and mechanical properties. Although some results have been achieved, there is still the problem of the unstable regeneration effect. The scaffold-free strategy believes that the limitations of scaffolds will have adverse effects on regenerative therapy. Therefore, the design of scaffold-free constructs relies as much as possible on the ability of cells to generate and maintain extracellular matrix without interfering with cell-cell signals or introducing exogenous substances. However, there are some problems, such as poor stability, low mechanical strength and greater difficulty in operation. Biomimetic strategy and scaffoldfree strategy have different emphases, advantages and disadvantages, but they both have positive effects on growth plate cartilage regeneration. Therefore, subsequent studies, whether adopting a biomimetic strategy or a scaffold-free strategy, will focus on the continuous optimization of existing technologies in order to achieve effective growth plate cartilage regeneration therapy. [ABSTRACT FROM AUTHOR]

To investigate the feasibility of cylindrical costal osteochondral graft transplantation as a novel regenerative treatment in growth arrest. The medial portion of the proximal tibial growth plate of 6-week-old male New Zealand White rabbits was resected to establish an experimental model of partial growth plate injury. The rabbits were divided into four groups: no-treatment, bone wax transplantation, costal chondral graft, and costal osteochondral graft groups. Radiographic and micro-computed tomography scan results were analyzed to evaluate angular deformity of the tibia and bony bridge formation at the injury site. In addition, repair of the injured growth plate cartilage was assessed histologically at 4, 8, and 12 weeks postoperatively. Radiographic examination revealed that bone wax transplantation continuously decreased the medial proximal tibial angle (MPTA) while the costal chondral graft implantation reduced the decrease of MPTA at 12 weeks postoperatively. The costal osteochondral graft implantation recovered the MPTA, close to the normal. Histologically, the costal osteochondral grafts retained the MPTA in the injured site compared to costal chondral grafts. Additionally, hypertrophic chondrocytes were observed at the graft site in the costal osteochondral graft group at 12 weeks, suggesting that endochondral ossification may occur at the graft site similar to normal ossification. The fluorescence in situ hybridization analysis of osteochondral grafts transplanted from male to female rabbits indicated that they were replaced by cells of host origin. The costal osteochondral graft can achieve regeneration without bony bridge formation in partial growth plate injury. [ABSTRACT FROM AUTHOR]

OBJECTIVE The growth arrest of epiphyseal plates is an inevitable complication of radiotherapy in most pediatric cancer patients, yet our understanding of the regulatory mechanisms governing the recovery response remains limited. This experiment sought to delve into the roles of yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) transcriptional co-activators, crucial drivers of the regenerative process, in this recovery response. METHODS In the study, thirty-six 8-week-old male rabbits underwent radiotherapy targeting the left distal femur and proximal tibia growth plates, while the right extremity served as an unirradiated control. The rabbits were divided into six groups based on post-irradiation time points (1, 7, 10, 14, 17, and 21 days). Histomorphological assessments through hematoxylin-eosin staining and immunohistochemical labeling of PTHrP, YAP1, and TAZ were conducted on the excised growth plates from both irradiated and unirradiated sides. RESULTS The initial week post-radiotherapy exhibited arresting effects, including increased apoptosis, reduced proliferative activity, and disruption of the columnar structure. Evidence of the recovery response, characterized by regenerative chondrocyte clones, became evident around day 10 and peaked on day 14. Subsequently, cellular and structural degeneration prevailed, with a transition to osteogenesis in the following days. The radiation notably decreased the nuclear immunopositivity ratio of the three molecules. While nuclear expression levels of YAP1 and TAZ initially declined within the 1st week, they subsequently rebounded sharply, though not reaching control levels. CONCLUSION These preliminary findings suggest that YAP1 and TAZ could play a pivotal role as regulators in the recovery response of growth plates following irradiation. [ABSTRACT FROM AUTHOR]

The growth plate is a cartilaginous tissue with three distinct zones. Resident chondrocytes are highly organized in a columnar structure, which is critical for the longitudinal growth of immature long bones. Once injured, the growth plate may potentially be replaced by bony bar formation and, consequently, cause limb abnormalities in children. It is well-known that the essential step in growth plate repair is the remolding of the organized structure of chondrocytes. To achieve this, we prepared an anatomy-inspired bionic Poly(ε-caprolactone) (PCL) scaffold with a stratified structure using three-dimensional (3D) printing technology. The bionic scaffold is engineered by surface modification of NaOH and collagen Ⅰ (COL Ⅰ) to promote cell adhesion. Moreover, chondrocytes and bone marrow mesenchymal stem cells (BMSCs) are loaded in the most suitable ratio of 1:3 for growth plate reconstruction. Based on the anatomical structure of the growth plate, the bionic scaffold is designed to have three regions, which are the small-, medium-, and large-pore-size regions. These pore sizes are used to induce BMSCs to differentiate into similar structures such as the growth plate. Remarkably, the X-ray and histological results also demonstrate that the cell-loaded stratified scaffold can successfully rebuild the structure of the growth plate and reduce limb abnormalities, including limb length discrepancies and angular deformities in vivo. This study provides a potential method of preparing a bioinspired stratified scaffold for the treatment of growth plate injuries.

The repair of growth plate injuries is a highly complex process that involves precise spatiotemporal regulation of multiple cell types. While significant progress has been made in understanding the pathological mechanisms underlying growth plate injuries, effectively regulating this process to regenerate the injured growth plate cartilage remains a challenge. Tissue engineering technology has emerged as a promising therapeutic approach for achieving tissue regeneration through the use of functional biological materials, seed cells and biological factors, and it is now widely applied to the regeneration of bone and cartilage. However, due to the unique structure and function of growth plate cartilage, distinct strategies are required for effective regeneration. Thus, this review provides an overview of current research on the application of tissue engineering to promote growth plate regeneration. It aims to elucidates the underlying mechanisms by which tissue engineering promotes growth plate regeneration and to provide novel insights and therapeutic strategies for future research on the regeneration of growth plate. [ABSTRACT FROM AUTHOR]

Introduction: Growth plate injury is a significant challenge in clinical practice, as it could severely affect the limb development of children, leading to limb deformity. Tissue engineering and 3D bioprinting technology have great potential in the repair and regeneration of injured growth plate, but there are still challenges associated with achieving successful repair outcomes.Methods: In this study, GelMA hydrogel containing PLGA microspheres loaded with chondrogenic factor PTH(1–34) was combined with BMSCs and Polycaprolactone (PCL) to develop the PTH(1–34)@PLGA/BMSCs/GelMA-PCL scaffold using bio-3D printing technology.Results: The scaffold exhibited a three-dimensional interconnected porous network structure, good mechanical properties, biocompatibility, and was suitable for cellchondrogenic differentiation. And a rabbit model of growth plate injury was appliedto validate the effect of scaffold on the repair of injured growth plate. The resultsshowed that the scaffold was more effective than injectable hydrogel in promotingcartilage regeneration and reducing bone bridge formation. Moreover, the addition ofPCL to the scaffold provided good mechanical support, significantly reducing limbdeformities after growth plate injury compared with directly injected hydrogel.Discussion: Accordingly, our study demonstrates the feasibility of using 3D printed scaffolds for treating growth plate injuries and could offer a new strategy for the development of growth plate tissue engineering therapy.

We report the entrapment of the extensor tendons following a growth plate fracture of the distal radius in a teenager. It is difficult to detect tendon entrapment at the fracture site immediately after the injury and diagnosis is typically made after fracture union when patients present with an inability to extend the thumb/reduced digital movement. A careful examination of our patient demonstrated some loss of digital motion and the plain radiographs, and computed tomographic scan showed incomplete reduction suggesting tendon entrapment. Early detection of the entrapped tendons allowed prompt release averting the need for tendon reconstruction. This report highlights the need for clinicians to maintain a high index of suspicion for tendon entrapment in patients with distal radius fractures that present with limited digital motion associated with incomplete reduction. An early diagnosis followed by the timely release can result in excellent outcomes. Level of Evidence: Level V (Therapeutic) [ABSTRACT FROM AUTHOR]

The proximal tibia physis’ anterior growth arrest is the cause of the uncommon condition known as acquired genu recurvatum, which can also be congenital, idiopathic, or secondary to trauma, infections, cerebrovascular accidents, or neuromuscular diseases. In order to avoid the reported drawbacks that could complicate osteotomies—incomplete correction, patella infera, knee pain or stiffness, and the requirement to remove plate metalwork—physeal distraction and callotasis with external fixation has been suggested. We present the case of a 14-year-old boy who had a 5 cm difference in limb length, with the right leg being shorter, and a right knee that was 30° recurved with flexion restriction beyond 40°. The correction was made in 50 days, and the external fixator was removed in 92 days after we performed a physeal distraction with an axial EF (ST.A.R., Citieffe) through an anterior physeal osteotomy just proximal to the tuberosity in conjunction with simultaneous asymmetrical tibial and femoral contralateral epiphysiodesys. The patient returned to playing football within 8 months despite the persistence of a 3 cm leg length discrepancy and had a symmetric full range of motion of the knee without any complications or persistent pain. The correction of genu recurvatum in adolescents may be achieved safely and effectively through physeal distraction with an axial external fixator.

[Display omitted] • Exo-AMG shows promise for treating growth plate injuries by promoting cartilage regeneration. • It fosters a conducive microenvironment of growth plate regeneration. • It suppresses inflammation, and enhances BMSC proliferation and chondrogenic differentiation. The growth plate is vital for childhood development, and most of the injuries can formation of bone bridges on it, which has negative impact on limb development. Current biomaterial scaffolds often lack essential cartilage matrix components, which hurdles to get an acceptable regeneration. Additionally, stem cell transplantation faces challenges including high apoptosis rates and uncertain differentiation. Then, we designed an injectable composite hydrogel (Exo-AMG) loaded with exosomes (Exo) and composed of methacrylate-modified acellular cartilage matrix (ACMMA) and gelatin methacrylate (GelMA) to repair the growth plate for children and adolescents. The hydrogel is administered via minimally invasive injection and undergoes in-situ photocrosslinking to fill the growth plate defects. It exhibited suitable mechanical properties, biodegradation rates; it also could sustain exosome release. Moreover, it promoted M2 macrophage polarization and secretion of anti-inflammatory factors, and it enhanced bone mesenchymal stem cells (BMSCs) proliferation and chondrogenic differentiation in vitro. In vivo study, this Exo-AMG induced growth plate cartilage regeneration without bone bridge formation. Therefore, this injectable and in-situ photocrosslinkable composite hydrogel is promising on growth plate injury repair by alleviating inflammation and promoting chondrogenic differentiation. [ABSTRACT FROM AUTHOR]

Postnatal bone growth primarily relies on chondrocyte proliferation and osteogenic differentiation within the growth plate (GP) via endochondral ossification. Despite its importance, the GP is vulnerable to injuries, affecting 15-30 % of bone fractures. These injuries may lead to growth discrepancies, influence bone length and shape, and negatively affecting the patient's quality of life. This study aimed to investigate the molecular and cellular physiological and pathophysiological regeneration following sustained growth plate injury (GPI) in an ex vivo rat femur organotypic culture (OTC) model. Specifically, focusing on postnatal endochondral ossification process. 300 μm thick ex vivo bone cultures with a 2 mm long horizontal GPI was utilized. After 15 days of cultivation, gene expression analysis, histological and immunohistochemistry staining's were conducted to analyze key markers of endochondral ossification. In our OTCs we observed a significant increase in Sox9 expression due to GPI at day 15. The Ihh-PTHrP feedback loop was affected, favoring chondrocyte proliferation and maturation. Ihh levels increased significantly on day 7 and day 15, while PTHrP was downregulated on day 7. GPI had no impact on osteoclast number and activity, but gene expression analysis indicated OTCs' efforts to inhibit osteoclast differentiation and activation, thereby reducing bone resorption. In conclusion, our study provides novel insights into the molecular and cellular mechanisms underlying postnatal bone growth and regeneration following growth plate injury (GPI). We demonstrate that chondrocyte proliferation and differentiation play pivotal roles in the regeneration process, with the Ihh-PTHrP feedback loop modulating these processes. Importantly, our ex vivo rat femur organotypic culture model allows for the detailed investigation of these processes, providing a valuable tool for future research in the field of skeletal biology and regenerative medicine., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Inappropriate treatment of growth plate injury may cause complications such as malunion or early arrest of the growth plate. Identification of intra-articular lesions is mandatory in patients with a growth plate injury of the distal tibia. Arthroscopic assessment is useful in identifying intra-articular injury. We report three cases of intra-articular growth plate injury of the distal tibia that were treated via internal fixation with arthroscopic assessment in our hospital. Materials and Methods: All three cases were performed pre- and postoperative arthroscopic assessment and open reduction and internal fixation with a cannulated cancellous screw (CCS; Meira, Japan). All patients were then examined for postoperative complications, functional recovery, at the end of the final follow-up consultation. Results: Intraoperatively, a small cartilage injury was found in the non-fracture area in two cases; the remaining case had a reversed cartilage fragment at the talus, which was arthroscopically removed. Conclusions: Arthroscopic assessment followed by internal fixation is a useful minimally invasive method for the identification of intra-articular lesions such as osteochondral injury or free bodies. [ABSTRACT FROM AUTHOR]

The proximal tibia physis' anterior growth arrest is the cause of the uncommon condition known as acquired genu recurvatum, which can also be congenital, idiopathic, or secondary to trauma, infections, cerebrovascular accidents, or neuromuscular diseases. In order to avoid the reported drawbacks that could complicate osteotomies--incomplete correction, patella infera, knee pain or stiffness, and the requirement to remove plate metalwork--physeal distraction and callotasis with external fixation has been suggested. We present the case of a 14-year-old boy who had a 5 cm difference in limb length, with the right leg being shorter, and a right knee that was 30° recurved with flexion restriction beyond 40°. The correction was made in 50 days, and the external fixator was removed in 92 days after we performed a physeal distraction with an axial EF (ST.A.R., Citieffe) through an anterior physeal osteotomy just proximal to the tuberosity in conjunction with simultaneous asymmetrical tibial and femoral contralateral epiphysiodesys. The patient returned to playing football within 8 months despite the persistence of a 3 cm leg length discrepancy and had a symmetric full range of motion of the knee without any complications or persistent pain. The correction of genu recurvatum in adolescents may be achieved safely and effectively through physeal distraction with an axial external fixator. [ABSTRACT FROM AUTHOR]

Abstract Faulty bony repair causes dysrepair of injured growth plate cartilage and bone growth defects in children; however, the underlying mechanisms are unclear. Recently, we observed the prominent induction of neurotrophin‑3 (NT-3) and its important roles as an osteogenic and angiogenic factor promoting the bony repair. The current study investigated its roles in regulating injury site remodelling. In a rat tibial growth plate drill-hole injury repair model, NT-3 was expressed prominently in osteoblasts at the injury site. Recombinant NT-3 (rhNT-3) systemic treatment enhanced, but NT-3 immunoneutralization attenuated, expression of cartilage-removal proteases (MMP-9 and MMP-13), presence of bone-resorbing osteoclasts and expression of osteoclast protease cathepsin K, and remodelling at the injury site. NT-3 was also highly induced in cultured mineralizing rat bone marrow stromal cells, and the conditioned medium augmented osteoclast formation and resorptive activity, an ability that was blocked by presence of anti-NT-3 antibody. Moreover, NT-3 and receptor TrkC were induced during osteoclastogenesis, and rhNT-3 treatment activated TrkC downstream kinase Erk1/2 in differentiating osteoclasts although rhNT-3 alone did not affect activation of osteoclastogenic transcription factors NF-κB or NFAT in RAW 264.7 osteoclast precursor cells. Furthermore, rhNT-3 treatment increased, but NT-3 neutralization reduced, expression of osteoclastogenic cytokines (RANKL, TNF-α, and IL-1) in mineralizing osteoblasts and in growth plate injury site, and rhNT-3 augmented the induction of these cytokines caused by RANKL treatment in RAW 264.7 cells. Thus, injury site osteoblast-derived NT-3 is important in promoting growth plate injury site remodelling, as it induces cartilage proteases for cartilage removal and augments osteoclastogenesis and resorption both directly (involving activing Erk1/2 and substantiating RANKL-induced increased expression of osteoclastogenic signals in differentiating osteoclasts) and indirectly (inducing osteoclastogenic signals in osteoblasts). Graphical abstract Unlabelled Image Highlights • Injury site osteoblast-derived NT-3 has both direct and indirect roles in promoting growth plate injury site remodeling. • NT-3 enhances expression of MMP-9 and MMP-13 and osteoclast recruitment and function at the growth plate injury site. • NT-3 was induced in mineralizing BMSCs, and the conditioned medium augmented osteoclastogenesis and resorptive activity. • NT-3 can induce osteoclastogenic cytokines and RANKL in osteoblasts. • NT-3 and TrkC were induced, and rhNT-3 treatment activated TrkC downstream kinase Erk1/2 in differentiating osteoclasts. [ABSTRACT FROM AUTHOR]

Injury to the growth plate is associated with growth disturbances, most notably premature cessation of growth. The goal of this study was to identify spatial changes in the structure and composition of the growth plate in response to injury to provide a foundation for developing therapies that minimize the consequences for skeletal development. We used contrast-enhanced microcomputed tomography (CECT) and histological analyses of a murine model of growth plate injury to quantify changes in the cartilaginous and osseous tissue of the growth plate. To distinguish between local and global changes, the growth plate was divided into regions of interest near to and far from the injury site. We noted increased thickness and CECT attenuation (a measure correlated with glycosaminoglycan (GAG) content) near the injury, and increased tissue mineral density (TMD) of bone bridges within the injury site, compared to outside the injury site and contralateral growth plates. Furthermore, we noted disruption of the normal zonal organization of the physis. The height of the hypertrophic zone was increased at the injury site, and the relative height of the proliferative zone was decreased across the entire injured growth plate. These results indicate that growth plate injury leads to localized disruption of cellular activity and of endochondral ossification. These local changes in tissue structure and composition may contribute to the observed retardation in femur growth. In particular, the changes in proliferative and hypertrophic zone heights seen following injury may impact growth and could be targeted when developing therapies for growth plate injury. [ABSTRACT FROM AUTHOR]

Growth plate injuries over the distal femur typically occur due to high-energy trauma. It is commonly associated with serious complications such as growth disturbance. Its occurrence in children undergoing limb-lengthening procedures is uncommon. We report a case of distal femur growth plate injury in a 13-year-old boy undergoing a limb-lengthening procedure for femoral hypoplasia. Conservative treatment yielded a good functional outcome in this patient., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Esmat et al.)

Purpose: The purpose of this study was to investigate the effects of transplantation of an in vitro-generated, scaffold-free, tissueengineered cartilage tissue analogue (CTA) using a suspension chondrocyte culture in a rabbit growth-arrest model. Materials and Methods: We harvested cartilage cells from the articular cartilage of the joints of white rabbits and made a CTA using a suspension culture of 2107 cells/mL. An animal growth plate defect model was made on the medial side of the proximal tibial growth plate of both tibias of 6-week-old New Zealand white rabbits (n=10). The allogenic CTA was then transplanted onto the right proximal tibial defect. As a control, no implantation was performed on the left-side defect. Plain radiographs and the medial proximal tibial angle were obtained at 1-week intervals for evaluation of bone bridge formation and the degree of angular deformity until postoperative week 6. We performed a histological evaluation using hematoxylin-eosin and Alcian blue staining at postoperative weeks 4 and 6. Results: Radiologic study revealed a median medial proximal tibial angle of 59.0° in the control group and 80.0° in the CTA group at 6 weeks. In the control group, statistically significant angular deformities were seen 3 weeks after transplantation (p<0.05). On histological examination, the transplanted CTA was maintained in the CTA group at 4 and 6 weeks postoperative. Bone bridge formation was observed in the control group. Conclusion: In this study, CTA transplantation minimized deformity in the rabbit growth plate injury model, probably via the attenuation of bone bridge formation. [ABSTRACT FROM AUTHOR]

Background: To elucidate the association between growth plate injury size and the beginning of physeal growth disturbance by MRI. Methods: Thirty-two 5-week-old male Japanese white rabbits were used. Injuries were made to the right tibial proximal growth plate central region with a 3.0-mm and a 1.2-mm drill. The left tibia was used as a control. MRI (7.04 Tesla [T], gradient echo: repetition time [TR], 71.68 ms; echo time [TE], 3.60 ms; proton-density weighted imaging: TR, 2000 ms; TE, 12 ms) of the growth plates was performed at 1, 4, 8, 10, and 12 weeks postinjury. Tibia length, histology, radiography, and microcomputed tomography (µCT) were studied. Results: MRI showed that at 10 and 12 weeks postinjury in the 3.0-mm group, the medial and lateral growth plates in the noninjured regions were significantly reduced compared with the controls (P < 0.05). At 12 weeks postinjury in the 1.2-mm group, medial and lateral growth plates in the noninjured regions were significantly reduced (P < 0.05). Tibia length and histological growth plate height of injured side in both groups were significantly shorter than controls at 12 weeks postinjury (P < 0.05). Comparison with the controls showed no significant difference at any of the time periods in either the 3.0- or 1.2-mm group according to the radiographic studies (P > 0.05). Bony bridges developed in all the subjects of the 3.0-mm group and in five of eight subjects of the 1.2-mm group, as shown by µCT images. Conclusion: This study suggested that growth plate injury size was associated with the timing of the beginning of physeal growth disturbance. [ABSTRACT FROM AUTHOR]

Recent breakthroughs in cell transplantation therapy have revealed the promising potential of bone marrow mesenchymal stem cells (BMSCs) for promoting the regeneration of growth plate cartilage injury. However, the high apoptosis rate and the uncertainty of the differentiation direction of cells often lead to poor therapeutic effects. Cells are often grown under three-dimensional (3D) conditions in vivo, and the stiffness and components of the extracellular matrix (ECM) are important regulators of stem cell differentiation. To this end, a 3D cartilage-like ECM hydrogel with tunable mechanical properties was designed and synthesized mainly from gelatin methacrylate (GM) and oxidized chondroitin sulfate (OCS) via dynamic Schiff base bonding under UV. The effects of scaffold stiffness and composition on the survival and differentiation of BMSCs in vitro were investigated. A rat model of growth plate injury was developed to validate the effect of the GMOCS hydrogels encapsulated with BMSCs on the repair of growth plate injury. The results showed that 3D GMOCS hydrogels with an appropriate modulus significantly promoted chondrogenic differentiation of BMSCs, and GMOCS/BMSC transplantation could effectively inhibit bone bridge formation and promote the repair of damaged growth plates. Accordingly, GMOCS/BMSC therapy can be engineered as a promising therapeutic candidate for growth plate injury.

Injuries to the growth plate cartilage often lead to bony repair, resulting in bone growth defects such as limb length discrepancy and angulation deformity in children. Currently utilised corrective surgeries are highly invasive and limited in their effectiveness, and there are no known biological therapies to induce cartilage regeneration and prevent the undesirable bony repair. In the last 2 decades, studies have investigated the cellular and molecular events that lead to bony repair at the injured growth plate including the identification of the four phases of injury repair responses (inflammatory, fibrogenic, osteogenic and remodelling), the important role of inflammatory cytokine tumour necrosis factor alpha in regulating downstream repair responses, the role of chemotactic and mitogenic platelet-derived growth factor in the fibrogenic response, the involvement and roles of bone morphogenic protein and Wnt/B-catenin signalling pathways, as well as vascular endothelial growth factor-based angiogenesis during the osteogenic response. These new findings could potentially lead to identification of new targets for developing a future biological therapy. In addition, recent advances in cartilage tissue engineering highlight the promising potential for utilising multipotent mesenchymal stem cells (MSCs) for inducing regeneration of injured growth plate cartilage. This review aims to summarise current understanding of the mechanisms for growth plate injury repair and discuss some progress, potential and challenges of MSC-based therapies to induce growth plate cartilage regeneration in combination with chemotactic and chondrogenic growth factors and supporting scaffolds. [ABSTRACT FROM AUTHOR]

Growth plate injuries often result in undesirable bony repair causing bone growth defects, for which the underlying mechanisms are unclear. Whilst the key importance of pro-angiogenic vascular endothelial growth factor (VEGF) is well-known in bone development and fracture repair, its role during growth plate bony repair remains unexplored. Using a rat tibial growth plate injury repair model with anti-VEGF antibody, Bevacizumab, as a single i.p. injection (2.5 mg/kg) after injury, this study examined the roles of VEGF-driven angiogenesis during growth plate bony repair. Histology analyses observed isolectin-B4-positive endothelial cells and blood vessel-like structures within the injury site on days 6 and 14, with anti-VEGF treatment significantly decreasing blood-vessel-like structures within the injury site (P!0.05). Compared with untreated controls, anti-VEGF treatment resulted in an increase in undifferentiated mesenchymal repair tissue, but decreased bony tissue at the injury site at day 14 (P!0.01). Consistently, microcomputed tomography analysis of the injury site showed significantly decreased bony repair tissue after treatment (P!0.01). RT-PCR analyses revealed a significant decrease in osteocalcin (P!0.01) and a decreasing trend in Runx2 expression at the injury site following treatment. Furthermore, growth plate injury-induced reduced tibial lengthening was more pronounced in anti-VEGF-treated injured rats on day 60, consistent with the observation of a significantly increased height of the hypertrophic zone adjacent to the growth plate injury site (P!0.05). These results indicate that VEGF is important for angiogenesis and formation of bony repair tissue at the growth plate injury site as well as for endochondral bone lengthening function of the uninjured growth plate. [ABSTRACT FROM AUTHOR]

ABSTRACT The skeleton of a subadult individual from the medieval graveyard of La Madeleine (Orléans, France) exhibits varus deformity of its right humerus. The affected bone is shortened, the diaphysis is angulated and the head is grossly deformed. The skeleton is otherwise normal. Several diagnoses are debated, including mucopolysaccharidoses, thalassemia, infection and trauma, the latter being preferred. The severity of the bone changes suggests that the growth disturbance occurred early in the life of the individual. We therefore suppose that the causative trauma occurred at the time of birth or during the early postnatal period. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Injuries to growth plates may initiate the formation of reversible or irreversible bone-bridges, may leading to bone length discrepancy or axis deviation. As vascular invasion is essential for the formation of bone tissue, the aim of our study was to investigate the kinetic expression of Vascular Endothelial Growth Factor (VEGF) and its receptors R1 and R2 and the ingrowth of vessels in the formation of bone bridges in a rat physeal injury model. Quantitative Real-Time Polymerase Chain Reaction was performed for VEGF and its receptors. Samples from the proximal physis of the tibial bone were immunohistochemically evaluated for the expression of VEGF and its R1 and R2 receptors and Laminin. Morphologically, physeal bone bridge formation was validated by means of Magnetic Resonance Imaging. Kinetic expression of VEGF and VEGF-R1 mRNA documented a tendency towards an increase in expression on day 7. Histological analyses showed a hematoma containing bone debris on day 1 which was replaced with bony trabeculae by day 14, forming a bone bridge by day 28 which was preceded and accompanied by angiogenesis and consistent with MRI data. VEGF and VEGF-R2 was expressed on the debris within the hematoma and bone trabeculae from days 1 to 28. VEGF-R1 expression was only noted until day 14. The findings of our study suggest that physeal bone bridge formation is in part triggered by VEGF expression and associated with angiogenesis, which was shown to precede bone bridge formation and may be further stimulated through VEGF-positive bone debris. [ABSTRACT FROM AUTHOR]

Abstract: Injuries to the growth plate remain a significant clinical challenge. The need to better understand mechanisms of growth disruption following transphyseal injuries and evaluate new therapeutic approaches to growth restoration motivates development of a well characterized model of growth plate injury. The goals of this study were to develop a growth plate defect model in the rat and to use microcomputed tomography (micro-CT) imaging to detect and quantify associated changes in growth plate morphology and mineralization over time following injury and in response to treatment. Three-dimensional images of the growth plate were created from micro-CT scans and used to quantify the volume of mineralized tissue within the defect site. Growth plate thickness and volume as well as the degree of growth plate fusion were also measured from the reconstructed 3D images. Growth deficiency was then quantified as a function of time post-injury from whole limb micro-CT scans. Finally, this model was used to determine the ability of an injectable in situ gelling hydrogel to prevent formation of a bony bridge within the defect and the subsequent effect on limb length deficiency and changes to growth plate morphology. Growth plate injury resulted in significant shortening of the defect limb by day 28 and significant thinning and fusion of the surrounding growth plate up to day 112. Limb length reduction was correlated with changes in the growth plate volume and average thickness at day 56. Injection of an in situ gelling agarose into the defect resulted in a reduction of limb length discrepancy as well as a thicker growth plate on average compared to empty defect controls. These results establish a novel method of characterizing changes in whole bone and growth plate morphology due to a growth plate injury and indicate that treatment with agarose hydrogel reduces limb length discrepancy but is not sufficient to regenerate growth plate tissue or fully restore growth function. [Copyright &y& Elsevier]

Abstract: Two cases of asymmetrical closure of the proximal tibial epiphysis without a clear aetiological factor were presented. In both cases premature closure of the growth plate resulted in progressive recurvatum and valgus deformity of the knee with leg length discrepancy. The correction of deformity was obtained using Taylor Spatial frame with excellent results at 2 years follow-up. We hypothesize that repetitive trauma or chronic overloading during sports activities might be a factor of growth arrest in reported cases. Orthopedic surgeons should be aware of the possibility of subtle physeal injuries, causing angular deformities, in the cases of even minor knee trauma in skeletally immature population. [Copyright &y& Elsevier]

In 12 patients affected by thalassemia major who received an intensive transfusion regimen combined with continuous iron chelation therapy (desferrioxamine 50-80 mg/kg daily), radiologic abnormalities of the long bones were observed similar to those observed in rickets and scurvy. These abnormalities were associated with a growth retardation. The pathogenesis of these lesions is uncertain, but probably the toxic effect of desferrioxamine plays an important role in their development. A relative deficiency of vitamins D and/or C cannot be entirely excluded. [ABSTRACT FROM AUTHOR]

Adolescents are at risk of unique ankle fracture patterns due to closing physes. Transitional ankle fractures, in particular, are an entity specific to adolescent patients due to the asymmetrically open distal tibia physis. Transitional ankle fractures are rarely seen in combination with bimalleolar ankle fracture patterns. This case is of interest because the combined fracture pattern and the treatment method presented have not been previously reported in the literature to our knowledge. A 15-year-old female presented with right ankle pain after a fall while roller skating. Imaging demonstrated a right Tillaux fracture with ipsilateral displaced medial malleolus fracture and minimally displaced Weber C distal fibula fracture. The Tillaux fracture and medial malleolus fractures were treated with open reduction and internal fixation with partially threaded compression screws. The lateral malleolus remained minimally displaced and did not require operative fixation. The patient healed well with no complications. Transitional injuries of the ankle in adolescents have been reported in the literature; however, combined injuries are uncommon and lack representation in the current literature base. These combined injuries are important to be aware of, as missed injuries can result in long-term pain and disability., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Helmig et al.)

Extravasation injuries are frequent complications, especially in extremely preterm neonates treated in neonate intensive care units (NICU). Depending on the type of the extravasated substance, the duration, and the amount of the leak, extravasation may result in necrosis of the soft tissues adjacent to the leak, compartment syndrome, and limb amputation. However, in some cases, the results of extravasation may be evident years after NICU treatment. In this case report, we describe a rare case of physeal arrest of the distal tibia in a preterm and discuss the possible causes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Samelis et al.)

Growth plate injury of the proximal humerus is rare. We herein report a traumatic growth plate injury of the proximal humerus in an elite diving athlete. A 16-year-old female diving athlete injured her left shoulder during 7.5 m platform hands-first diving practice. At the first visit, she presented with upper left shoulder tenderness and left shoulder range-of-motion limitation. There was no fracture or dislocation on X-ray and computed tomography (CT), but magnetic resonance imaging (MRI) showed a high-intensity zone in the left lateral epiphysis of the proximal humerus. We treated her conservatively by rest with sling and rehabilitation. She partially restarted diving practice five weeks post-injury and returned to competition eight weeks post-injury. Even if there is no sign of fracture or dislocation, we should consider MRI for patients who are before the age of growth plate closure., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Asai et al.)