Aims. Accurate skeletal age and final adult height prediction methods in paediatric orthopaedics are crucial for determining optimal timing of growth-guiding interventions and minimizing complications in treatments of various conditions. This study aimed to evaluate the accuracy of final adult height predictions using the central peak height (CPH) method with long leg X-rays and four different multiplier tables. Methods. This study included 31 patients who underwent temporary hemiepiphysiodesis for varus or valgus deformity of the leg between 2014 and 2020. The skeletal age at surgical intervention was evaluated using the CPH method with long leg radiographs. The true final adult height (FH. TRUE. ) was determined when the growth plates were closed. The final height prediction accuracy of four different multiplier tables (1. Bayley and Pinneau; 2. Paley et al; 3. Sanders – Greulich and Pyle (SGP); and 4. Sanders – peak height velocity (PHV)) was then compared using either skeletal age or chronological age. Results. All final adult height predictions overestimated the FH. TRUE. , with the SGP multiplier table having the lowest overestimation and lowest absolute deviation when using both chronological age and skeletal age. There were no significant differences in final height prediction accuracy between using skeletal age and chronological age with PHV (p = 0.652) or SGP multiplier tables (p = 0.969). Adult height predictions with chronological age and SGP (r = 0.769; p ≤ 0.001), as well as chronological age and PHV (r = 0.822; p ≤ 0.001), showed higher correlations with FH. TRUE. than predictions with skeletal age and SGP (r = 0.657; p ≤ 0.001) or skeletal age and PHV (r = 0.707; p ≤ 0.001). Conclusion. There was no significant improvement in adult height prediction accuracy when using the CPH method compared to chronological age alone. The study concludes that there is no advantage in routinely using the CPH method for skeletal age determination over the simple use of chronological age. The findings highlight the need for more accurate methods to predict final adult height in contemporary patient populations. Cite this article: Bone Jt Open 2023;4(10):750–757

The concept of guided growth was proposed by Andry in 1741. In the last decades the concept has been widely used as implants has been introduced that can modulate the growth of the bone and pediatric longitudinal and angular deformities is widely treated by this technique. However, there is there is a huge variation in techniques and implants used and high-quality clinical trials is still lacking. Recently implants correcting rotational bony deformities have been proposed and clinical case series have been published. The current status of guided growth will be presented in this narrative review and preliminary experiences with rotational guided growth will be shared. Is guided growth to be considered a safe treatment at this time point?

Purpose. Angular deformity in the lower extremities can result in pain, gait disturbance, cosmetic deformity and joint degeneration. Up until the introduction of guided growth in 2007, which has since become the gold standard, treatment for correcting angular deformities in skeletally immature patients had been either an osteotomy, a hemiepiphysiodesis, or the use of staples. Methods. We reviewed the surgical records and diagnostic imaging in our childrens hospital to identify all patients who had guided growth surgery since 2007. All patients were followed until skeletal maturity or until their metalwork was removed. Results. 113 patients, with 147 legs were assessed for eligibility. Three were excluded for various reasons including inadequate follow-up or loss of records. Of the 144 treated legs which met the criteria for final assessment 32 (22.2%) were unsuccessful, the other 112 (77.8%) were deemed successful at final follow up. Complications were few, but included infection in one case and metal failure in another. Those with a pre-treatment diagnosis of idiopathic genu valgum/genu varum had a success rate of 83.6%. Conclusions. In our hands, guided growth had a seventy-eight percent success rate when all diagnosis were considered. Those procedures that were unlikely to be successful included growth disturbances due to mucopolysaccharide storage disease (28% failure rate), Blounts disease (66.6% failure rate) and achondroplasia (37.5% failure rate). If you exclude those three diagnoses, success rate for all other conditions was 81.4%. We continue to advocate the use of guided growth as a successful treatment option for skeletally immature patients with limb deformity

Abstract. Aims. Growth disturbances after transphyseal paediatric ACL reconstruction have led to the development of physeal-sparing techniques. However, evidence in their favour remains weak. This study reviews the literature to identify factors associated with growth disturbances in paediatric ACL reconstructions. Materials and Methods. Web of Science, Scopus and Pubmed were searched for case series studying paediatric ACL reconstructions. Titles, abstracts, text, results and references were examined for documentation of growth disturbances. Incidences of graft failures were also studied in these selected studies. Results. 78 studies with 2693 paediatric ACL reconstructions had 70 growth disturbances (2.6%). Of these 17 were varus, 26 valgus, 13 shortening, 14 lengthening and 5 patients had reduced tibial slope. Coronal plane deformities were seen more frequently with eccentric physeal arrest and lengthening with intraepiphyseal tunnelling. Shortening and reduced tibial slope were related to large central physeal arrest and anterior tibial physeal arrest respectively. Extraphyseal technique were least likely to have growth disturbances. 62 studies documented 166 graft failures in 2120 patients (7.83%). Conclusion. Growth disturbances resulting from transphyseal ACL reconstruction can be minimised by keeping drill size small, drilling steep and away from the physeal periphery. Insertion of bone plug, hardware or synthetic material through the drilled physis should be avoided. The evidence to accurately quantify such growth disturbances till skeletal maturity remains weak. Robust long term studies such as national ligament registries may standardise preoperative and postoperative outcome assessment to further characterise the risk of growth disturbance and re-ruptures

Aims. Osteoarthritis (OA) is the most prevalent systemic musculoskeletal disorder, characterized by articular cartilage degeneration and subchondral bone (SCB) sclerosis. Here, we sought to examine the contribution of accelerated growth to OA development using a murine model of excessive longitudinal growth. Suppressor of cytokine signalling 2 (SOCS2) is a negative regulator of growth hormone (GH) signalling, thus mice deficient in SOCS2 (Socs2. -/-. ) display accelerated bone growth. Methods. We examined vulnerability of Socs2. -/-. mice to OA following surgical induction of disease (destabilization of the medial meniscus (DMM)), and with ageing, by histology and micro-CT. Results. We observed a significant increase in mean number (wild-type (WT) DMM: 532 (SD 56); WT sham: 495 (SD 45); knockout (KO) DMM: 169 (SD 49); KO sham: 187 (SD 56); p < 0.001) and density (WT DMM: 2.2 (SD 0.9); WT sham: 1.2 (SD 0.5); KO DMM: 13.0 (SD 0.5); KO sham: 14.4 (SD 0.7)) of growth plate bridges in Socs2. -/-. in comparison with WT. Histological examination of WT and Socs2. -/-. knees revealed articular cartilage damage with DMM in comparison to sham. Articular cartilage lesion severity scores (mean and maximum) were similar in WT and Socs2. -/-. mice with either DMM, or with ageing. Micro-CT analysis revealed significant decreases in SCB thickness, epiphyseal trabecular number, and thickness in the medial compartment of Socs2. -/-. , in comparison with WT (p < 0.001). DMM had no effect on the SCB thickness in comparison with sham in either genotype. Conclusion. Together, these data suggest that enhanced GH signalling through SOCS2 deletion accelerates growth plate fusion, however this has no effect on OA vulnerability in this model. Cite this article: Bone Joint Res 2022;11(3):162–170

Vertebral growth remains a mystery, especially with regards to the contribution of different growth plates and the mechanisms of growth after closure of these plates. As an example of vertebral growth in general, the growth of the vertebral canal was assessed in a rat model using fluorochromes. Although 80–90% of vertebral canal growth was due to growth plates, the remaining canal growth occurred via periosteal absorption and deposition. This is contrary to the traditional idea that periosteal mechanisms do not change the shape or dimensions of bone and suggests that the vertebrae exhibit a different model of growth than typical bones. Vertebral growth remains largely a mystery. The contributions of different growth plates and the mechanisms of growth after closure of these plates requires further exploration. As an example of vertebral growth, vertebral canal growth was assessed in a living rat model using fluorochromes. Vertebral canal growth and presumably vertebral growth in general occurred by different mechanisms at different phases of development. Growth plates accounted for the majority of growth although periosteal mechanisms also resulted in changes in the size and shape of the vertebrae. This is contrary to the traditional concept of periosteal growth and suggests that vertebrae may exhibit a different model of growth than typical bones. The growth of the vertebrae in a particular dimension and during a particular phase of development is dependent on different mechanisms of growth, which may play a role in interpreting vertebral growth anomalies. The interspinous junction closed by the end of the first week, whereas the neurocentral junction closed between weeks three and four. By four weeks, the vertebral canal had achieved 80–90% of its growth in area and diameter. After growth plate closure, the canal continued to grow by periosteal mechanisms and was displaced posteriorly. Thirty-six Sprague-Dawley rats (age one week-seven weeks) were injected with tetracycline and alizarin using a dosing interval of four days. Thoracic vertebrae were sectioned using a cryostat and examined under a fluorescence microscope. In addition to noting fluoro-chrome deposition, the dimensions of the growth plates and canal were noted. Funding: Edmonton Orthopaedic Research Association and University of Alberta Department of Radiology and Diagnostic Imaging

Introduction. Genu valgum is a common presentation in paediatric patients with congenital limb deformities. The aim of this study is to assess the outcome of guided growth surgery in paediatric patients referred via our physiotherapy pathway with isolated genu valgum and associated patellar instability. Materials & Methods. Patients were identified from our prospective patellar instability database. Inclusion criteria was acquired or congenital genu valgum associated with patellar instability in skeletally immature patients. The mechanical lateral-distal femoral angle was assessed on long leg alignment radiographs (mLDFA <85 degrees). Surgical treatment was the placement of a guided growth plate (PediPlate, OrthoPediatrics, USA) on the medial distal femoral physis (hemi-epiphysiodesis). KOOS-child scores were collected pre-operatively and post-operatively (minimum at 6 months). Results. Eleven patients (seven female) with mean age of 12(range 5–15) were identified. Five patients had congenital talipes equinovarus(CTEV), one fibular hemimelia, one di-George syndrome, one septic growth arrest and three had idiopathic genu valgum. Pre- and post-operative KOOS-child scores showed overall improvement: 58(range 36–68) to 88(65–99) and knee symptoms subscores: 64(43–71) to 96(68–100) p<0.01, t-test. Mean follow-up was 10 months (range 3–23). No subsequent dislocations/subluxations occurred during follow-up. Conclusions. Guided growth surgery is an effective way of treating symptomatic patellar instability in skeletally immature patients with genu valgum in the absence of other structural pathology. It was most common in our cohort in patients with unilateral CTEV. We would recommend to screen syndromic and congenital limb deformity patients for patellar instability symptoms in the presence of genu valgum

Problems of vertebral growth plate metabolism regulation at different stages of ontogenesis are insufficiently covered in the literature. However, the study of function mechanism of provisional cartilage of vertebral growth plate is a practical and theoretical basis of pathogenesis model of idiopathic scoliosis and Scheuermann’s disease both associated with growth disorders. Objective: To investigate the function mechanism of vertebral growth plate structural components during formation and growth. Materials and methods: Fifty vertebral body specimens of children at the age from 1 to 14 years obtained from the forensic medicine department were studied by methods of morphohistochemistry, biochemistry, and ultra-structural analysis. The expression of five proteoglycan genes and their albuminous products was investigated by RT-PCR method. Results: The process of growth represents a sequence of morphogenetic movements ongoing up to the achievement of sexual maturity. But morphofunctional organization and regulation of growth are different in different periods of ontogenesis. Early postnatal growth of vertebral bodies is governed by a radially located zone of growth. The cell population in a just-formed cartilage growth plate is non-uniform: from poorly differentiated chondroblast through the form of highly differentiated ones to degrading chondrocyte. This period of the spine development is characterised by the presence of vessels in provisional cartilage tissue. The concept of “chondro/hematic barrier” suggested and validated by A.M Zaidman explains a conservation of homeostasis at a stage of vertebral bodies differentiation. The process of chondrogenic differentiation of prechondroblasts in the early postnatal period is inducted by the chorda influence. In the late postnatal period (12–14 years) the laws of structural and functional organization of cartilage growth plate of vertebral body remain the same: phenotypic heterogeneity, polarity, and zonality of cells. A metabolic centre of complex architectonics of cartilage tissue is chondroblast. Chondroblast is functioning at the level of chondron which is a functional unit of vertebral growth plate. Chondroblast (chondrocyte) is located in the centre of chondron and surrounded by pericellular matrix presented by diffuse aggrecan molecules, or growth plate aggregates. Due a peculiar architectonics, growth plate molecules have inner spaces comparable in size with Golgi’s vesicles. Metabolites, small molecules, and water freely penetrate through these molecules. Diffuse molecules together with type II thin collagenic fibres, minor collagenes, and structure-forming growth plates perform barrier function. Besides barrier function, diffuse molecules perform information function inside a chondron, forming a kind of information field. Signals of this field are perceived by chondroblast receptors, and the cell gene apparatus expression is carried out through second messengers. Thus, either stimulation of proliferative activity with subsequent differentiation during intensive growth, or interruption of these processes (period of growth delay) occurs. Single chondrons unite into chains in proliferation zones. Cell interaction inside chondron occurs due transmembrane structures, as a contact coordination of functions of cells with inherent high specificity. Concentration of diffuse molecules of growth plate (aggrecan) in proliferation zones is the highest on evidence of histochemical and ultrastructural assays. Besides, diffuse molecules are the short-distance regulators of DNA synthesis the mechanism of action of which is realised through the system of receptors on a cellular membrane. Hence, contact intercellular interactions are one of the mechanisms controlling cell division. These are so-called extracellular factors of chondroblast proliferation regulation. Thus, the process of growth represents a complex two-stage mechanism of proliferation and differentiation of chondroblasts, and adequate osteogenesis. All three processes provide harmonious spine formation, and disturbance of one of them results in pathology development

Introduction. Current treatments of rotational deformities of long bones in children are osteotomies and fixations. In recent years, the use of guided growth for correction of rotational deformities has been reported in several pre-clinical and clinical studies. Various techniques have been used, and different adverse effects, like growth retardation and articular deformities, have been reported. We tested a novel plate concept intended for correction of rotational deformities of long bones by guided growth, with sliding screw holes to allow for longitudinal growth, in a porcine model. Method. Twelve, 12-week-old female porcines were included in the study. Surgery was performed on the left femur. The right femur was used as control. Plates were placed distally to induce external rotation, as longitudinal growth occurred. CT-scans of the femurs were processed to 3-D models and used for measuring rotation. Result. The plates rotated as intended in all 12 porcines. One porcine was excluded due to congenital deformity of the proximal part of the femurs. Two porcines had cut-out of the proximal screw on the lateral side, observed at the end of the intervention. These two porcines were included in the results. We observed a Δrotation of 5.7° ± 2° in external direction (CI: 3.7°– 7.7°). ΔFemur length was -0.4 cm [-0.7 cm – 0 cm] equal to 1.5% shortening of the operated femur. No significant difference was observed in coronal or sagittal plane. Conclusion. Significant external rotation was achieved with minimal effect on longitudinal growth. While the use of guided growth for correction of rotational deformities is already being used clinically, it is still to be considered an experimental procedure with sparse evidence. This study shows promising results for the feasibility of the method in a large animal model and is an important first step in validating the technique and detecting possible adverse effects, before future clinical studies

The aim of this scoping review is to understand the extent and type of evidence in relation to the use of guided growth for correcting rotational deformities of long bones. Guided growth is routinely used to correct angular deformities in long bones in children. It has also been proven to be a viable method to correct rotational deformities, but the concept is not yet fully examined. Databases searched include Medline, Embase, Cochrane Library, Web of Science and Google Scholar. All identified citations were uploaded into Rayyan.ai and screened by at least two reviewers. The search resulted in 3569 hits. 14 studies were included: 1 review, 3 clinical trials and 10 pre-clinical trials. Clinical trials: a total of 21 children (32 femurs and 5 tibiae) were included. Surgical methods were 2 canulated screws connected by cable, PediPlates obliquely oriented, and separated Hinge Plates connected by FiberTape. Rotation was achieved in all but 1 child. Adverse effects reported include limb length discrepancy (LLD), knee stiffness and rebound of rotation after removal of tethers. 2 pre-clinical studies were ex-vivo studies, 1 using 8-plates on Sawbones and 1 using a novel z-shaped plates on human cadaver femurs. There were 5 lapine studies (2 using femoral plates, 2 using tibial plates and 1 using an external device on tibia), 1 ovine (external device on tibia), 1 bovine (screws and cable on metacarp) and a case-report on a dog that had an external device spanning from femur to tibia. Rotation was achieved in all studies. Adverse effects reported include implant extrusions, LLD, articular deformities, joint stiffness and rebound. All included studies conclude that guided growth is a viable treatment for rotational deformities of long bones, but there is great variation in models and surgical methods used, and in reported adverse effects

Herein we address, hyaline cartilage regeneration issue by engineering a synthetic biocompatible hydrogel scaffold capable to promote chondrogenic differentiation. In this study, the chemically crosslinked hydrogels consisting of synthetic peptides that have the collagen-like sequence Cys-Gly-(Pro-Lys-Gly)4 (Pro-Hyp-Gly)4 (Asp-Hyp-Gly)4- conjugated with RGD sequence (CLP-RGD) and crosslinked hydrogels of type I collagen (CA) were used. For cartilage formation, we used human skeletal muscle-derived stem/progenitor cells (hMDSPCs) set for differentiation towards a chondrogenic lineage by BMP-7 and TGF-ß3 growth factors. Initially 150, 100 and 75 ng of BMP-7and TGF-ß3 growth factors were inserted in each scaffold and amount of growth factors diffusing out of the scaffolds was observed by ELISA assays. In vitro experiments were performed by seeding hMDSPCs onto hydrogels loaded with growth factors (75ng/scaffold) and cultured for 28 days. Cartilage formation was monitored by ELISA and RT-PCR assays. All experiments were performed in triplicates or quadruplicates. Growth factors incorporation strategy allowed a sustained release of TGF-ß3 growth factor, 6.00.3% of the initially loaded amount diffused out after 4 h and 2.70.5% already at the second time point (24h) from CA and CLP-RGD substrates. For the BMP-7 growth factor, 13.12.3% and 15.751.6% of the initially loaded amount diffused out after 4 h, 1.70.2% and 2.450.3% at the second time point (24 h) from CA and CLP-RGD respectively. In vitro experiments shown that scaffolds with immobilized growth factors resulted in higher collagen type II accumulation when compared to the scaffolds alone. The gene expression on CLP-RGD hydrogels with growth factors has shown lower collagen type I expression and higher aggrecan expression compared to day 0. However, we also report increased collagen X gene expression on CA hydrogels (with growth factors). Our results support the potential of the strategy of combining hydrogels functionalized with differentiation factors toward improving cartilage repair

Cells typically respond to a variety of geometrical cues in their environment, ranging from nanoscale surface topography to mesoscale surface curvature. The ability to control cellular organisation and fate by engineering the shape of the extracellular milieu offers exciting opportunities within tissue engineering. Despite great progress, however, many questions regarding geometry-driven tissue growth remain unanswered. Here, we combine mathematical surface design, high-resolution microfabrication, in vitro cell culture, and image-based characterization to study spatiotemporal cell patterning and bone tissue formation in geometrically complex environments. Using concepts from differential geometry, we rationally designed a library of complex mesostructured substrates (10. 1. -10. 3. µm). These substrates were accurately fabricated using a combination of two-photon polymerisation and replica moulding, followed by surface functionalisation. Subsequently, different cell types (preosteoblasts, fibroblasts, mesenchymal stromal cells) were cultured on the substrates for varying times and under varying osteogenic conditions. Using imaging-based methods, such as fluorescent confocal microscopy and second harmonic generation imaging, as well as quantitative image processing, we were able to study early-stage spatiotemporal cell patterning and late-stage extracellular matrix organisation. Our results demonstrate clear geometry-dependent cell patterning, with cells generally avoiding convex regions in favour of concave domains. Moreover, the formation of multicellular bridges and collective curvature-dependent cell orientation could be observed. At longer time points, we found clear and robust geometry-driven orientation of the collagenous extracellular matrix, which became apparent with second harmonic generation imaging after ∼2 weeks of culture. Our results highlight a key role for geometry as a cue to guide spatiotemporal cell and tissue organisation, which is relevant for scaffold design in tissue engineering applications. Our ongoing work aims at understanding the underlying principles of geometry-driven tissue growth, with a focus on the interactions between substrate geometry and mechanical forces

Introduction. The proteoglycan aggrecan is a major component of the cartilaginous matrices which provides resistance against compressive forces. Spontaneously occurring functional null mutations in the aggrecan gene (Acan) in various species lead to perinatal chondrodysplasia. The aim of the present study was to investigate the cellular and biomechanical properties of the cartilaginous growth plate, and the development of intervertebral disc in a novel, experimentally induced aggrecan mutant mouse strain carrying an insertion in exon 5 of the Acan gene. Methods. The novel aggrecan mutant mice were generated by inserting a loxP site into exon 5 (E5i) by homologous recombination in ES cells. Wild type and homozygous mutant (Acan-E5i/E5i) mice were analyzed by skeletal staining, histology and immunohistochemistry. Proliferation and survival were assessed by phosphorylated histone H3 immunostaining and TUNEL assay, respectively. Shape index (SI) in the proliferative zone (PZ) of the growth plate (GP) was calculated as a ratio of the long and short axes of the cells. Orientation of the PZ chondrocytes was characterized by the angle between the cell long axis and longitudinal direction of the bone growth. Imaging and stiffness measurements were performed by atomic force microscopy (AFM). Results. Acan-E5i/E5i mice are characterized by severe dwarfism, short snout, protruding tongue, cleft palate, and die at birth due to respiratory failure. On sections the cartilage of mutant mice appeared as tightly packed chondrocytes surrounded by a compressed matrix. At E18.5 and E14.5, the mutant PZ consisted of rounded (SI=1.71 at E18.5; SI=1.72 at E14.5) non-oriented chondrocytes, compared to the wild type PZ with flattened (SI=3.92 at E18.5; SI=3.90 at E14.5), columnar cells oriented with right angle to the longitudinal axis of the growth. At E13, the shape and orientation of mutant chondrocytes were similar to control. AFM at E14.5 and E18.5 demonstrated a stiffer matrix with denser collagen network in the mutant compared to wild type. The mutant cartilage had increased apoptosis and reduced proliferation rate at E18.5. The IVDs development appeared normal at E13.5-E14.5, however, the IVD was severely malformed at E18.5. Discussion. We have shown that aggrecan deficiency impairs cartilage biomechanics and results in a stiffer matrix. The altered mechanical properties might be responsible for the disorganization of mutant GP and compression of the IVD at around birth. Interestingly, the altered matrix mechanics is dispensable for early flattening and orientation of GP proliferative chondrocytes. In summary, aggrecan is essential for proper cartilage cytoarchitecture and morphogenesis by ensuring the suitable mechanical environment

Introduction. Angular deformity in the lower extremities can result in pain, gait disturbance, deformity and joint degeneration. Guided growth modulation uses the tension band principle with the goal of treatment being to normalise the mechanical axis. To assess the success of this procedure we reviewed our results in an attempt to identify patients who may not benefit from this simple and elegant procedure. Materials and Methods. We reviewed the surgical records and imaging in our tertiary children's hospital to identify all patients who had guided growth surgery since 2007. We noted the patient demographics, diagnosis, peri-operative experience and outcome. All patients were followed until skeletal maturity or until metalwork was removed. Results. 173 patients with 192 legs were assessed for eligibility. Six were excluded due to inadequate follow-up or loss of records. Of the 186 treated legs meeting criteria for final assessment 19.8% were unsuccessful, the other 80.2% were deemed successful at final follow up. Complications included infection and metal-work failure. Those with a pre-treatment diagnosis of idiopathic genu valgum/ varum had a success rate of 83.6%. Conclusions. In our hands, guided growth had an 80-percent success rate when all diagnosis were considered. Those procedures that were unlikely to be successful included growth disturbances due to mucopolysaccharide storage disease, Blounts disease and achondroplasia. Excluding those three diagnoses, success rate was 85.4%. We continue to advocate the use of guided growth as a successful treatment option for skeletally immature patients with limb deformity

Background. Despite aggressive debridement, thorough irrigation, administration of systemic antibiotics and staged treatment, many open fractures still become infected. A graft that can promote bone regeneration and prevent infection could decrease complications. Polyurethane (PUR) scaffolds have been previously shown in separate studies to be non-toxic, osteoconductive, can promote bone growth through BMP delivery and prevent infection by having sustained release of an antibiotic. This scaffold can deliver both BMP and vancomycin simultaneously; the purpose of this study is to determine if the co-delivery of the antibiotic inhibits bone formation. Methods. Using an established critical size defect rat femur model, the amount of bone formation created by PUR scaffolds containing low and high doses of rhBMP-2 (2.4 μg and 22.4 μg respectively) and 0.8 mg vancomycin (8% of graft by weight) were compared to scaffolds that contained rhBMP-2 without antibiotics. After 4 weeks, the femurs were harvested and bone growth was assessed using microCT. Results. There were no significant differences in bone growth between the groups that had the high dose of rhBMP-2. Surprisingly, the scaffolds that had the low dose of rhBMP-2 and vancomycin promoted more bone formation than scaffolds that had rhBMP-2 and no antibiotics. Conclusions. The addition and co-delivery of vancomycin to the scaffolds did not inhibit bone growth. The addition of vancomycin to the PUR scaffolds may have altered the release kinetics of the rhBMP-2; this may explain the increase of bone formation in this group. This study demonstrates that incorporation of a therapeutic and a clinically-relevant level of vancomycin does not inhibit bone formation. These results suggest that a dual delivery bone graft has potential to reducing complications associated with open fractures

Re-rupture rates after rotator cuff repair remain high because of inadequate biological healing at the tendon-bone interface. Single-growth factor therapies to augment healing at the enthesis have so far yielded inconsistent results. An emerging approach is to combine multiple growth factors over a spatiotemporal distribution that mimics normal healing. We propose a novel combination treatment of insulin-like growth factor 1 (IGF-1), transforming growth factor β1 (TGF-β1) and parathyroid hormone (PTH) incorporated into a controlled-release tyraminated poly-vinyl-alcohol hydrogel to improve healing after rotator cuff repair. We aimed to evaluate this growth factor treatment in a rat chronic rotator cuff tear model. A total of 30 male Sprague-Dawley rats underwent unilateral supraspinatus tenotomy. Delayed rotator cuff repairs were then performed after 3 weeks, to allow tendon degeneration that resembles the human clinical scenario. Animals were randomly assigned to: [1] a control group with repair alone; or [2] a treatment group in which the hydrogel was applied at the repair site. All animals were euthanized 12 weeks after rotator cuff surgery and the explanted shoulders were analyzed for biomechanical strength and histological quality of healing at the repair site. In the treatment group had significantly higher stress at failure (73% improvement, P=0.003) and Young's modulus (56% improvement, P=0.028) compared to the control group. Histological assessment revealed improved healing with significantly higher overall histological scores (10.1 of 15 vs 6.55 of 15, P=0.032), and lower inflammation and vascularity. This novel combination growth factor treatment improved the quality of healing and strength of the repaired enthesis in a chronic rotator cuff tear model. Further optimization and tailoring of the growth factors hydrogel is required prior to consideration for clinical use in the treatment of rotator cuff tears. This novel treatment approach holds promise for improving biological healing of this clinically challenging problem

Introduction. Herein, a tri-layered core-shell microfibrous scaffold with layer-specific growth factors (GFs) release is developed using coaxial electrohydrodynamic (EHD) printing for in situ cell recruitment and differentiation to facilitate gradient enthesis tissue repair. Our findings suggest that the microfibrous scaffolds with layer-specific GFs release may offer a promising clinical solution for enthesis regeneration. Method. Utilizing coaxial electrohydrodynamic (EHD) printing, we engineered tri-layered core-shell microfibrous scaffolds, each layer tailored with specific growth factors (GFs) for targeted enthesis tissue repair. This configuration aims to sequentially guide cell migration and differentiation, mirroring the natural enthesis’ gradient structure. SDF-1 was strategically loaded into the shell, while bFGF, TGF-β, and BMP-2 were encapsulated in the core, each selected for their roles in stimulating the regeneration of corresponding enthesis tissue layers. Result. The coaxial EHD-printed microfibrous scaffolds demonstrated a core-shell fiber width of 24.3 ± 6.3 μm, supporting distinct tenogenic, chondrogenic, and osteogenic layers with pore sizes of 81.5 ± 4.6 μm, 173.3 ± 6.9 μm, and 388.9 ± 6.9 μm, respectively. This structure facilitated a targeted and effective release of growth factors, optimizing stem cell recruitment and differentiation. In vivo assessments demonstrated that the scaffolds significantly enhanced biomechanical properties and facilitated the formation of gradient enthesis structures, with improved biomechanical strength approximately 2-3 times that of control groups. These results highlight the scaffold's capability to mimic the native enthesis structure, encouraging a conducive environment for cell-mediated repair and regeneration. Conclusion. The integration of layer-specific growth factors not only fostered a conducive environment for tissue regeneration but also exemplified a leap in the design of scaffolds that closely mimic the native tendon-to-bone interface. The findings illuminate the scaffold's capacity to direct cellular behavior and tissue formation, heralding a new era in regenerative strategies and offering a promising avenue for clinical translation in the treatment of rotator cuff injuries

In recent years numerous growth factors acting on musculoskeletal tissues have been identified. This presentation summarizes our experience with IGF1 in the stimulation of growth of the physis and TGF beta in the formation of bone and cartilage. IGF1 in a carrier, agarose, was instilled in a paraphsyeal region in rabbit tibias. The physeal height was measured over a period of time and was found to have increased in the group treated with IGF1 when compared to the control group. In addition there was delayed closure of the physeal plate. These findings may have clinical applications in stimulation of physeal growth in small by length discrepancies. A polycaprolactone scaffold impregnated with TGF beta was implanted under the skin, in the muscle and under the periosteum in rabbits. Over a period of time the scaffolds were harvested and subjected to histological analysis with a variety to stains. Formation of bone and cartilage was found in these scaffolds implanted under the periosteum. Subdermal and intramuscular implantation of the scaffolds did not produce the same results. It is postulated that apart from TGF Beta local and environmental factors may play a part in bone and cartilage formation. This model may be useful in creating complex scaffolds in-vivo for subsequent transplantations

Background: Despite aggressive debridement, thorough irrigation, systemic antibiotics, and staged treatment, many open fractures still become infected. A graft that can promote bone regeneration and prevent infection could decrease complications. Polyurethane (PUR) scaffolds have previously been shown in separate studies to be nontoxic, osteoconductive, can promote bone growth by delivering BMP, and prevent infection by the sustained release of an antibiotic. This scaffold can deliver both BMP and vancomycin simultaneously; the purpose of this study is to determine if the co-delivery of the antibiotic inhibits bone formation. Methods: Using an established critical size defect rat femur model, the amount of bone formation created by PUR scaffolds containing low and high doses of rhBMP-2 (2.4 μg and 22.4 μg respectively) and 0.8 mg vancomycin (8% of graft by weight) were compared to scaffolds that contained rhBMP-2 without antibiotics. After 4 weeks, the femurs were harvested and bone growth was assessed using microCT. Results: There was no significant difference in bone growth between the groups that had the high dose of rhBMP-2. Surprisingly, the scaffolds that had the low dose of rhBMP-2 and vancomycin promoted more bone formation than scaffolds that had rhBMP-2 and no antibiotics. Conclusions: The addition and co-delivery of vancomycin to the scaffolds did not inhibit bone growth. The addition of vancomycin to the PUR scaffolds may have altered the release kinetics of the rhBMP-2; this may explain the increase of bone formation in this group. This study demonstrates that incorporation of a therapeutic and a clinically-relevant level of vancomycin does not inhibit bone formation. These results suggest that a dual delivery bone graft has potential to reducing complications associated with open fractures

Introduction. To evaluate the results of correction of knee deformities based on deformity analysis in Achondroplasia, the commonest skeletal dysplasia as some have concomitant ligamentous deformities. Materials and Methods. Retrospective study from a prospective database (2007–2020) of achondroplasts who underwent growth modulation. Analysis of medical records with objective measurement of mechanical axis radiographs was done (Traumacad). Satisfactory alignment was defined as neutral to slightly varus (0–15 mm MAD) so that the MCL/LCL laxity is not revealed. Results. 23 patients, 41 limbs, 34 bilateral, 6 unilateral underwent multiple growth modulation procedures. 2 had valgus knees. 15 patients underwent proximal fibular epiphysiodesis in addition for LCL laxity with one isolated fibular epiphysiodesis. Mechanical axis deviation (MAD) improved or normalised in 16 patients (70%). 4 patients were still undergoing correction. 4 patients needed further surgery out of which 2 patients were over 13 years when growth modulation was attempted and 2 needed correction of ankle varus. JLCA improved/ normalised in 12 patients (75%) with evidence of indirect LCL tightening and no improvement was seen in 4. The rate of correction was MAD 0.61mm/month, LDFA 0.29°/month and MPTA 0.13°/month; expectedly lower in achondroplasia due to lower growth velocity. Conclusions. This study highlights the pathology, application of growth modulation as per deformity analysis unlike previous studies. Proximal fibular epiphysiodesis improves LCL laxity in a majority of these children and is a simple procedure compared to our published series with indirect LCL tightening with frames