Growth Plate Injury Research Articles

Evaluation of the effect of osteosynthesis wires on the structural reorganization of metaepiphyseal cartilage (an experimental and morphological study)

Introduction Premature arrest of bone growth is the most common complication of bone fractures at the growth plate level.The purpose of the work was to evaluate the structural reorganization of metaepiphyseal cartilage following its direct injury with metal and biodegradable wires in an experiment.Materials and methods The metaepiphyseal cartilage of the distal femur of 18 lambs of both sexes was studied. The age of the animals at the beginning of the study was (43.92 ± 0.8) days, by 60 and 120 days (102.63 ± 0.82) and (161.1 ± 0.9) days, respectively. The animals underwent transphyseal insertion of wires/ pins: series 1 — Kirschner wires, series 2 — titanium wires, series 3 — poly-L-lactic acid pins. The duration of the experiment was 60 and 120 days. Clinical and radiographic studies were carried out. Histomorphometry was performed using an AxioScope.A1 microscope and Zenblue software (CarlZeissMicroImagingGmbH, Germany).Results Reactive changes in the growth plate at the interface with the wire were manifested by proliferation of chondrocytes in the zone of proliferating cartilage and in the reserve zone; the minimally expressed changes were noted in series 2, the most pronounced were in series 1. By the end of the experiment, at the interface with the wire in series 1, blood vessels penetrated into the metaepiphyseal cartilage; in series 3 the amount of the fibrous component was increased, which indicates further formation of “bone bridges” and “fibrous bridges,” respectively. In undamaged areas of the growth plate in all series, the zonal structure was preserved. By the end of the experiment, increased values of the thickness of the metaepiphyseal cartilage were noted (1.2 times higher than the control), differences between series were a tendency; in series 2 and 3 the ratio of metaepiphyseal cartilage zones was comparable to the control; in series 1 the proportion of the proliferating cartilage zone was increased by 4 %.Discussion The main problem with growth plate injuries is the formation of bone tissue or fibrosis, which affects the growing process. Currently, the question of choosing a treatment tactic for growth plate injury depending on the size of the “bone bridges” is debatable. Relevant are future comparative studies of the regeneration of metaepiphyseal cartilage defects after the use of fixators made from different materials.Conclusion Histomorphometric characteristics of the growth zone reliably showed that the insertion of wires, regardless of their material, was not accompanied by inhibition of the bone-forming function of the distal metaepiphyseal cartilage of the femur.

Sustained release of MAPK14-targeting siRNA from polyelectrolyte complex hydrogels mitigates MSC osteogenesis in vitro with potential application in growth plate injury.

The growth plate is a cartilage structure at the end of long bones which mediates growth in children. When fractured, the formation of bony repair tissue known as a "bony bar" can occur and cause limb deformities. There are currently no effective clinical solutions for the prevention of the bony bar formation or regeneration of healthy growth plate cartilage after a fracture. This study employs previously developed alginate/chitosan polyelectrolyte complex (PEC) hydrogels as a sustained release vehicle for the delivery of short-interfering RNA (siRNA). Specifically, the siRNA targets the p38-MAPK pathway in mesenchymal stem cells (MSCs) to prevent their osteogenic differentiation. In vitro experimental findings show sustained release of siRNA from the hydrogels for 6 months. Flow cytometry and confocal imaging indicate that the hydrogels release siRNA to effectively knockdown GFP expression over a sustained period. MAPK-14 targeting siRNA was used to knockdown the expression of MAPK-14 and correspondingly decrease the expression of other osteogenic genes in MSCs in vitro over the span of 21 days. These hydrogels were used in a rat model of growth plate injury to determine whether siMAPK-14 released from the gels could inhibit bony bar formation. No significant reduction of bony bar formation was seen in vivo at the one concentration of siRNA examined. This PEC hydrogel represents a significant advancement for siRNA sustained delivery, and presents an interesting potential therapeutic delivery system for growth plate injuries and other regenerative medicine applications.

Depletion of b-series ganglioside prevents limb length discrepancy after growth plate injury

IntroductionGrowth plate damage in long bones often results in progressive skeletal growth imbalance and deformity, leading to significant physical problems. Gangliosides, key glycosphingolipids in cartilage, are notably abundant in articular cartilage and regulate chondrocyte homeostasis. This suggests their significant roles in regulating growth plate cartilage repair.MethodsChondrocytes from 3 to 5 day-old C57BL/6 mice underwent glycoblotting and mass spectrometry. Based on the results of the glycoblotting analysis, we employed GD3 synthase knockout mice (GD3-/-), which lack b-series gangliosides. In 3-week-old mice, physeal injuries were induced in the left tibiae, with right tibiae sham operated. Tibiae were analyzed at 5 weeks postoperatively for length and micro-CT for growth plate height and bone volume at injury sites. Tibial shortening ratio and bone mineral density were measured by micro-CT.ResultsGlycoblotting analysis indicated that b-series gangliosides were the most prevalent in physeal chondrocytes among ganglioside series. At 3 weeks, GD3-/- exhibited reduced tibial shortening (14.7 ± 0.2 mm) compared to WT (15.0 ± 0.1 mm, P = 0.03). By 5 weeks, the tibial lengths in GD3-/- (16.0 ± 0.4 mm) closely aligned with sham-operated lengths (P = 0.70). Micro-CT showed delayed physeal bridge formation in GD3-/-, with bone volume measuring 168.9 ± 5.8 HU at 3 weeks (WT: 180.2 ± 3.2 HU, P = 0.09), but normalizing by 5 weeks.ConclusionThis study highlights that GD3 synthase knockout mice inhibit physeal bridge formation after growth plate injury, proposing a new non-invasive approach for treating skeletal growth disorders.

Implants removal in children: results of a survey among Italian orthopaedic surgeons.

In the treatment of paediatric limb disorders, the use of metal implants has been increasing over the last decades. Recent studies have addressed the decision of orthopaedic surgeons regarding the removal of implants after the treatment of fracture, and there is a growing consensus within the scientific community supporting the choice of not removing implants in children. This survey aimed to investigate the rationale behind the Italian orthopaedic community's decision regarding metal implant removal in paediatric patients. An electronic questionnaire was sent to all members of the Italian Paediatric Orthopaedic and Traumatology Society, Italian Orthopaedic and Traumatology Society, Italian Club of Osteosynthesis, and South Italy Society of Orthopaedic and Traumatology. The survey comprised 34 questions about hardware removal after the treatment of long bone fractures, epiphyseal growth plate injuries, slipped capital femoral epiphysis (SCFE), and flat foot. Of the 3500 orthopaedic surgeons who received the questionnaire, 5.5% responded. The leading indications for implant removal were the patient's intolerance, pain, ROM limitations, and hardware breakage. Removal of elastic nails for long bone fractures, cannulated screws for growth plate injuries, and SCFE and screws for arthroereisis for flat foot correction were analysed in detail. The consensus among Italian Orthopaedic Surgeons is to remove elastic nails and cannulated screws in cases of pain, intolerance, or breakage and to reduce further risks during patient growth. An increasing number of physicians, however, are endorsing and advocating the growing trend in the literature of not routinely removing the hardware.

Ex vivo organotypic bone slice culture reveals preferential chondrogenesis after sustained growth plate injury

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.

Clinical analysis of 1301 children with hand and foot fractures and growth plate injuries.

Fractures of hands and feet are common in children, but relevant epidemiological studies are currently lacking. We aim to study the epidemiological characteristics of hand and foot fractures and growth plate injuries in children and provide a theoretical basis for their prevention, diagnosis, and treatment. We retrospectively analyzed the data of children with hand and foot fractures who were hospitalized at Shenzhen Children's Hospital between July 2015 and December 2020. Data on demographic characteristics, fracture site, treatment method, etiology of injury, and accompanying injuries were collected. The children were divided into four age groups: infants, preschool children, school children, and adolescents. The fracture sites were classified as first-level (the first-fifth finger/toe, metacarpal, metatarsal, carpal, and tarsal) and second-level (the first-fifth: proximal phalanx, middle phalanx, distal phalanx, metacarpal, and metatarsal) sites. The changing trends in fracture locations and injury causes among children in each age group were analyzed. Overall, 1301 children (1561 fractures; 835 boys and 466 girls) were included. The largest number of fractures occurred in preschool children (n = 549, 42.20%), with the distal phalanx of the third finger being the most common site (n = 73, 15.57%). The number of fractures in adolescents was the lowest (n = 158, 12.14%), and the most common fracture site was the proximal phalanx of the fifth finger (n = 45, 29.61%). Of the 1561 fractures, 1143 occurred in the hands and 418 in the feet. The most and least common first-level fracture sites among hand fractures were the fifth (n = 300, 26.25%) and first (n = 138, 12.07%) fingers, respectively. The most and least common first-level foot fracture locations were the first (n = 83, 19.86%) and fourth (n = 26, 6.22%) toes, respectively. The most common first-level and second level etiologies were life related injuries (n = 1128, 86.70%) and clipping injuries (n = 428, 32.90%), respectively. The incidence of sports injuries gradually increased with age, accounting for the highest proportion in adolescents (26.58%). Hand and foot fractures had many accompanying injuries, with the top three being nail bed injuries (570 cases, 36.52%), growth plate injuries (296 cases, 18.96%), and distal severed fracture (167 cases, 10.70%). Among the 296 growth plate injuries, 246 occurred on the hands and 50 on the feet. In contrast to previous epidemiological studies on pediatric hand and foot fractures, we mapped the locations of these fractures, including proximal, shaft, distal, and epiphyseal plate injuries. We analyzed the changing trends in fracture sites and injury etiologies with age. Hand and foot fractures have many accompanying injuries that require attention during diagnosis and treatment. Doctors should formulate accident protection measures for children of different ages, strengthen safety education, and reduce the occurrence of accidental injuries.

3D-printed PCL scaffolds with anatomy-inspired bionic stratified structures for the treatment of growth plate injuries

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.

Prospective review of open reduction and internal fixation with Kirschner wires (K-wires left exposed) fixation in displaced and rotated (Song V) lateral humerus condyle fractures in children

Background: Fractures of the lateral condyle of the humerus account for 10-15% of all elbow fractures in children. These include Salter Harris type 2 and type 4 growth plate injuries in which the fracture crosses the distal humeral growth plate and enter the elbow joint. Open reduction and internal fixation with K wire is treatment of choice for the displaced as well as minimally displaced lateral condyle fractures of children to prevent malunion, nonunion and further displacement. Methods: This was prospective analytical study conducted in Rajendra Institute of Medical Sciences, Ranchi from December 2020 to December 2022 which consisted of 30 patients (of whom only 27 were present for follow ups) who were treated by ORIF with K-wires fixation. We followed the classification pattern given by Song et al. Results were evaluated according to the criteria given by the Hardacre et al. Results: Major culprit for injuries was fall from height (44.4%), followed by playing indoor games (25.9%). RTA and sports each constituted of (14.8%). Functional outcomes based on Hardacre criteria are excellent (85.1%), good in 11.1% cases and fair in 3.7% cases. Conclusions: Our findings demonstrate that open reduction and internal fixation with 2 or 3 K-wires (which were left exposed) and immobilization with casting for 3-4 weeks is sufficient for most of displaced and rotated fractures of the lateral condyle of the humerus.

Rotator Cuff Repair in Pediatric and Adolescent Athletes: Indications and Outcomes.

Rotator cuff (RC) tears in pediatric and adolescent athletes are rare events. In these patients, RC tears are more likely to be traumatic or related to overuse among overhead. Repeated movements of abduction and external rotation are frequent mechanisms of injury. The supraspinatus is the most commonly involved tendon and the articular-sided tears are more common than the bursal side. Magnetic resonance imaging is considered the gold standard for diagnosing RC tears. Conservative treatment, arthroscopic, and open repair are all effective treatment methods depending on the type of injury. The risk of growth plate injury in these patients should be always considered when planning surgical interventions. Return to sport for competitive-level throwing athletes represents the greatest challenge in the treatment of these injuries.

Disruption of Endochondral Ossification and Extracellular Matrix Maturation in an Ex Vivo Rat Femur Organotypic Slice Model Due to Growth Plate Injury.

Postnatal bone fractures of the growth plate (GP) are often associated with regenerative complications such as growth impairment. In order to understand the underlying processes of trauma-associated growth impairment within postnatal bone, an ex vivo rat femur slice model was developed. To achieve this, a 2 mm horizontal cut was made through the GP of rat femur prior to the organotypic culture being cultivated for 15 days in vitro. Histological analysis showed disrupted endochondral ossification, including disordered architecture, increased chondrocyte metabolic activity, and a loss of hypertrophic zone throughout the distal femur. Furthermore, altered expression patterns of Col2α1, Acan, and ColX, and increased chondrocyte metabolic activity in the TZ and MZ at day 7 and day 15 postinjury were observed. STEM revealed the presence of stem cells, fibroblasts, and chondrocytes within the injury site at day 7. In summary, the findings of this study suggest that the ex vivo organotypic GP injury model could be a valuable tool for investigating the underlying mechanisms of GP regeneration post-trauma, as well as other tissue engineering and disease studies.

3D bioprinted hydrogel/polymer scaffold with factor delivery and mechanical support for growth plate injury repair.

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.

Injectable hydrogel loaded with bilayer microspheres to inhibit angiogenesis and promote cartilage regeneration for repairing growth plate injury.

Introduction: The repair and regeneration of growth plate injuries using tissue engineering techniques remains a challenge due to large bone bridge formation and low chondrogenic efficiency. Methods: In this study, a bilayer drug-loaded microspheres was developed that contains the vascular endothelial growth factor (VEGF) inhibitor, Bevacizumab, on the outer layer and insulin-like growth factor-1 (IGF-1), a cartilage repair factor, on the inner layer. The microspheres were then combined with bone marrow mesenchymal stem cells (BMSCs) in the gelatin methacryloyl (GelMA) hydrogel to create a composite hydrogel with good injectability and biocompatibility. Results: The in vitro drug-release profile of bilayer microspheres showed a sequential release, with Bevacizumab released first followed by IGF-1. And this hydrogel simultaneously inhibited angiogenesis and promoted cartilage regeneration. Finally, in vivo studies indicated that the composite hydrogel reduced bone bridge formation and improved cartilage regeneration in the rabbit model of proximal tibial growth plate injury. Conclusion: This bilayer microsphere-based composite hydrogel with sequential controlled release of Bevacizumab and IGF-1 has promising potential for growth plate injury repair.

The regenerative treatment of costal osteochondral graft implantation for partial growth arrest using a rabbit model

PurposeTo investigate the feasibility of cylindrical costal osteochondral graft transplantation as a novel regenerative treatment in growth arrest. MethodsThe 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. ResultsRadiographic 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. ConclusionThe costal osteochondral graft can achieve regeneration without bony bridge formation in partial growth plate injury.

Double-Bundle Quadriceps Tendon Autograft for Reconstruction of the Medial Patellofemoral Complex to Manage Recurrent Patellar Dislocation in Patients With Open Physes

Management of chronic patellar instability in patients with open physis requires special reconstruction techniques to minimize the risks of femoral growth plate injury due to the close proximity of the open physis to the native femoral origin of the medial patellofemoral ligament (MPFL). Children and adolescents have a relatively smaller patella than the adult group, so, there is a higher risk of patellar fracture when tunnels are performed in the patella. It is wise to mimic the normal anatomy of the medial patellofemoral complex (MPFC) by reconstruction of both of the medial quadriceps tendon femoral ligament (MQTFL) and MPFL, so as to restore the normal fan-shaped MPFC, with its wide anterior attachment to both of the patella and quadriceps tendon (QT). This article describes a simple, safe, reproducible, and cost effective technique for surgical management of chronic patellar instability in patients with open physis by reconstruction of the MPFC using a double-bundle QT autograft.

Biodegradable Dual-Cross-Linked Hydrogels with Stem Cell Differentiation Regulatory Properties Promote Growth Plate Injury Repair via Controllable Three-Dimensional Mechanics and a Cartilage-like Extracellular Matrix.

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.

Research progress on the mechanism of interleukin-1β on epiphyseal plate chondrocytes

Epiphyseal plate injury, a common problem in pediatric orthopedics, may result in poor bone repair or growth defects. Epiphyseal plate, also known as growth plate is a layer of hyaline cartilage tissue between the epiphysis and metaphyseal and has the ability to grow longitudinally. Under normal physiological conditions, the epiphyseal plate has a certain axial resistance to stress, but it is fragile in growth phase and can be damaged by excessive stress, leading to detachment or avulsion of the epiphysis, resulting in life-long devastating consequences for patients. There is an obvious inflammatory response in the phase of growth plate injury, the limited physiological inflammatory response locally favors tissue repair and the organism, but uncontrolled chronic inflammation always leads to tissue destruction and disease progression. Interleukin-1β (IL-1β), as representative inflammatory factors, not only affect the inflammatory phase response to bone and soft tissue injury, but have a potentially important role in the later repair phase, though the exact mechanism is not fully understood. At present, epiphyseal plate injuries are mainly treated by corrective and reconstructive surgery, which is highly invasive with limited effectiveness, thus new therapeutic approaches are urgently needed, so a deeper understanding and exploration of the pathological mechanisms of epiphyseal plate injuries at the cellular molecular level is an entry point. In this review, we fully introduced the key role of IL-1 in the progression of epiphyseal plate injury and repair, deeply explored the mechanism of IL-1 on the molecular transcript level and endocrine metabolism of chondrocytes from multiple aspects, and summarized other possible mechanisms to provide theoretical basis for the clinical treatment and in-depth study of epiphyseal plate injury in children.

KLF2 reduces dexamethasone-induced injury to growth plate chondrocytes by inhibiting the Runx2-mediated PI3K/AKT and ERK signalling pathways

Dexamethasone (Dex) is a type of glucocorticoid drug. Long term use can induce growth plate chondrocytes (GPCs) apoptosis, impair differentiation, and inhibit cell proliferation and bone growth. It has been reported that Krüppel-like factor 2 (KLF2) inhibits osteoblast damage induced by Dex, but the role in Dex-induced GPCs remains unclear. Dex was used to construct a model of growth plate injury in vitro. CCK-8 and TUNEL kits were used to determine cell viability and apoptosis. A model of growth plate injury was established by intraperitoneal injection of Dex. Immunohistochemistry was used to investigate the expression of KLF2 in rats. The results showed that KLF2 expression of rat tibial GPCs was down-regulated after Dex stimulation. Overexpression of KLF2 promoted cell viability and cell cycle, while inhibited apoptosis of growth plate Dex-induced chondrocytes. Moreover, KLF2 inhibited Runx2-mediated PI3K/AKT and ERK signalling pathways. And PI3K/AKT and ERK signalling pathways, which were involved in the regulation of KLF2 on GPCs. Further studies showed that KLF2 alleviated growth plate injury in vivo. In conclusion, our study found that KLF2 promoted proliferation and inhibited apoptosis of Dex-induced GPCs by targeting the Runx2-mediated PI3K/AKT and ERK signalling pathways.

Successful conservative treatment for Ogden type-IV tibial tubercle avulsion fracture with transverse fibular fracture in 15 years old boy in remote area: a case report

Background: Tibial tubercle avulsion fracture is very rare. Its incidence has been reported to account for only 3% of all proximal tibia fractures and less than 1% of all growth plate injuries. This fracture occurs when the quadriceps are forcefully contracted against resistance, such as during jumping, or when rapid knee flexion occurs with contracted quadriceps, such as during landing. Most authors recommended surgical options in type IV tibial tubercle avulsion; however, we reported successful conservative treatment in this case report. Case report: A 15-year-old male athlete with no significant past medical history presented via emergency medical services after a ground-level fall while playing basketball which landed with his left foot in a pivot position. He felt immediate pain and swelling about the left knee, all sensation was intact, as were pedal pulses, and neurovascularly remained intact. The patient did not want to go for medical evacuation to do surgery and consent to be managed with conservative treatment with close follow-up. Conclusion: The results and prognosis of these fractures are excellent, despite the fracture pattern or treatment used, as long as an anatomical reduction is obtained

A 3D printed mimetic composite for the treatment of growth plate injuries in a rabbit model

Growth plate injuries affecting the pediatric population may cause unwanted bony repair tissue that leads to abnormal bone elongation. Clinical treatment involves bony bar resection and implantation of an interpositional material, but success is limited and the bony bar often reforms. No treatment attempts to regenerate the growth plate cartilage. Herein we develop a 3D printed growth plate mimetic composite as a potential regenerative medicine approach with the goal of preventing limb length discrepancies and inducing cartilage regeneration. A poly(ethylene glycol)-based resin was used with digital light processing to 3D print a mechanical support structure infilled with a soft cartilage-mimetic hydrogel containing chondrogenic cues. Our biomimetic composite has similar mechanical properties to native rabbit growth plate and induced chondrogenic differentiation of rabbit mesenchymal stromal cells in vitro. We evaluated its efficacy as a regenerative interpositional material applied after bony bar resection in a rabbit model of growth plate injury. Radiographic imaging was used to monitor limb length and tibial plateau angle, microcomputed tomography assessed bone morphology, and histology characterized the repair tissue that formed. Our 3D printed growth plate mimetic composite resulted in improved tibial lengthening compared to an untreated control, cartilage-mimetic hydrogel only condition, and a fat graft. However, in vivo the 3D printed growth plate mimetic composite did not show cartilage regeneration within the construct histologically. Nevertheless, this study demonstrates the feasibility of a 3D printed biomimetic composite to improve limb lengthening, a key functional outcome, supporting its further investigation as a treatment for growth plate injuries.

A New Method for Modeling Rabbit Growth Plate Injury for the Study of Tissue Engineering Scaffolds.

Establishing a suitable animal model of growth plate injury is necessary to evaluate the effect of tissue engineering scaffolds on repairing the injured growth plate. However, the currently used animal models have limitations. Therefore in this study, we reported and evaluated a new modeling method termed the longitudinal disruption method, which is to make a longitudinal defect in the region of growth plate. To compare this new method with the traditional transverse disruption method, we constructed the models by both methods, respectively. To observe whether bone bridges were formed, histological sections were analyzed by hematoxylin-eosin (HE) and Masson staining at 3 weeks after modeling. The HE and Masson staining results showed the formation of bone bridges in both groups, implying that the two methods successfully injured the growth plate. However, it was unclear whether the exact injury to growth plate caused by both methods was consistent. Therefore, to evaluate the accuracy and precision of modeling method, the X-ray and micro-computed tomography (CT) were performed immediately after modeling. The percentages of accurate defect position in the longitudinal and transverse modeling groups were 88.89% and 55.56%, respectively. The micro-CT results revealed irregularly shaped defect cross sections in the transverse modeling group, whereas the defects in the longitudinal modeling group had regular shapes. The mean defect areas were 10.06 ± 0.86 and 12.30 ± 2.13 mm2 in the longitudinal and transverse modeling groups, respectively, while the difference between the actual area and the expected area were -1.94 ± 0.86 and -7.70 ± 2.13 mm2, respectively, showing the high precision of this new method. Altogether, we successfully demonstrated a new method for establishing a rabbit model of growth plate injury, which provides a simple and rapid modeling process, good modeling effect, high modeling accuracy, and convenient scaffold implantation. The new method provides an effective animal model for tissue engineering research on the repair and regeneration of injured growth plate. Impact Statement In recent years, an increasing number of studies have used tissue engineering scaffolds in the repair and regeneration of growth plate. However, the currently used animal models have certain limitations in the study of tissue engineering scaffold for growth plate. In this study, a new method is presented to establish a rabbit model of growth plate injury. This method is characterized by simple and rapid modeling process, good modeling effect, high modeling accuracy, and convenient scaffold implantation, which is suitable for the study of the repair effects of tissue engineering scaffolds. Altogether, this method provides an effective animal model for tissue engineering research on growth plate and facilitates the development of tissue engineering research on the repair and regeneration of injured growth plate.