Skeletal Dysplasia Research Articles

3D Bioprinting Strategies for Melatonin‐Loaded Polymers in Bone Tissue Engineering

AbstractBone pathologies are still among the most challenging issues for orthopedics. Over the past decade, different methods are developed for bone repair. In addition to advanced surgical and graft techniques, polymer‐based biomaterials, bioactive glass, chitosan, hydrogels, nanoparticles, and cell‐derived exosomes are used for bone healing strategies. Owing to their variation and promising advantages, most of these methods are not translated into clinical practice. Three dimensonal (3D) bioprinting is an additive manufacturing technique that has become a next‐generation biomaterial technique adapted for anatomic modeling, artificial tissue or organs, grafting, and bridging tissues. Polymer‐based biomaterials are mostly used for the controlled release of various drugs, therapeutic agents, mesenchymal stem cells, ions, and growth factors. Polymers are now among the most preferable materials for 3D bioprinting. Melatonin is a well‐known antioxidant with many osteoinductive properties and is one of the key hormones in the brain–bone axis. 3D bioprinted melatonin‐loaded polymers with unique lipophilic, anti‐inflammatory, antioxidant, and osteoinductive properties for filling large bone gaps following fractures or congenital bone deformities may be developed in the future. This study summarized the benefits of 3D bioprinted and polymeric materials integrated with melatonin for sustained release in bone regeneration approaches.

Modulation of biomineralization morphology by phosphorylated collagen peptides: insights into osteogenesis imperfecta pathophysiology.

Osteogenesis imperfecta (OI) is a hereditary skeletal disorder characterized by bone fragility and deformities, primarily attributed to defects in type I collagen, the most abundant structural protein in humans. Multiple phosphorylation sites have been detected within collagen, suggesting that phosphorylation may influence mineralization processes, thereby impacting the development of OI. In this study, we investigated the modulation of biomineralization morphology by phosphorylated collagen peptides mimicking Gly-Ser mutations in osteogenesis imperfecta. A series of collagen peptide sequences, including GPO13S, GPO13pS, GPO12S, GPO12pS, GPO11S, and GPO11pS, were synthesized to explore the role of phosphorylation in peptide stability and its templating effect on biomineralization. The CD results indicated that the phosphorylation of Gly-pSer mutants reduces the stability of collagen peptides. SEM images revealed that phosphorylated peptides acted as templates, guiding the morphology of calcium carbonate into either olive-like or spherical structures, depending on their conformational state of the peptides. Non-phosphorylated peptides maintained a calcite crystal structure. The XRD patterns predominantly exhibited peaks associated with calcite and vaterite for GPO13pS-CaCO3, GPO12pS-CaCO3, and GPO11pS-CaCO3, and peaks associated with calcite for GPO13S-CaCO3, GPO12S-CaCO3, and GPO11S-CaCO3, indicating a transformation of mesocrystals influenced by peptide phosphorylation. Our findings elucidate the crucial role of phosphorylated collagen peptides in mediating biomineralization morphology and polymorph selection, offering insights into the complex pathophysiology of OI.

Growth plate closure and therapeutic interventions.

Height gains result from longitudinal bone growth, which is largely dependent on chondrocyte differentiation and proliferation within the growth plates of long bones. The growth plate, that is, the epiphyseal plate, is divided into resting, proliferative, and hypertrophic zones according to chondrocyte characteristics. The differentiation poten-tial of progenitor cells in the resting zone, continuous capacity for chondrocyte differentiation and proliferation within the proliferative zone, timely replacement by osteocytes, and calcification in the hypertrophic zone are the 3 main factors controlling longitudinal bone growth. Upon ade quate longitudinal bone growth, growth plate senescence limits human body height. During growth plate senescence, progenitor cells within the resting zone are deplet ed, proliferative chondrocyte numbers de crease, and hypertrophic chondrocyte number and size decrease. After senescence, hypertrophic chondrocytes are replaced by osteocytes, the extracellular matrix is calcified and va-scularized, the growth plate is closed, and longitudinal bone growth is complete. To date, go nadotropin-releasing hormone analogs, aromatase inhi bitors, C-type natriuretic peptide analogs, and fibroblast growth factor receptor 3 inhibitors have been studied or used as therapeutic interv-entions to delay growth plate closure. Complex networks of cellular, genetic, paracrine, and endocrine signals are involved in growth plate closure. However, the detailed mechanisms of this process remain unclear. Further eluci-dation of these mechanisms will enable the development of new thera peutic modalities for the treatment of short stature, precocious puberty, and skeletal dysplasia.

Familial osteochondrodysplastic and cardiomyopathic syndrome in Chianina cattle.

Skeletal dysplasia encompasses a heterogeneous group of genetic disorders characterized by an abnormal development of bones, joints, and cartilage. Two Chianina half-sibling calves from consanguineous mating with congenital skeletal malformations and cardiac abnormalities were identified. To characterize the disease phenotype, to evaluate its genetic cause, and to determine the prevalence of the deleterious alleles in the Chianina population. Two affected calves, their parents and 332 Chianina bulls. The affected animals underwent clinicopathological investigation. Whole-genome sequencing trio-approach and PCR-based assessment of the frequency of TDP-glucose 4,6-dehydratase (TGDS) and laminin subunit alpha 4 (LAMA4) alleles were performed. The cases presented with retarded growth, poor nutritional status associated with muscular atrophy and angular deformities of the hindlimbs. Radiologic examination identified generalized osteopenia and shortening of the limb long bones. Necropsy showed osteochondrodysplastic limbs and dilatation of the heart right ventricle. On histological examination, the physeal cartilages were characterized by multifocal mild to moderate loss of the normal columnar arrangement of chondrocytes. Osteopenia also was observed. Genetic analysis identified a missense variant in TGDS and a splice-site variant in LAMA4, both of which were homozygous in the 2 cases. Parents were heterozygous and allele frequency in the Chianina population for the TGDS variant was 5% and for the LAMA4 variant was 2%. Genetic findings identified 2 potentially pathogenic alleles in TGDS and LAMA4, but no clear mode of inheritance could be determined.

Case report: exome sequencing identified mutations in the LRP5 and LGR4 genes in a case of osteoporosis with recurrent fractures and extraskeletal manifestations

BackgroundGenetic mutations have been reported in a number of bone disorders with or without extra-skeletal manifestations. The purpose of the present study was to investigate the genetic cause in a middle-aged woman with osteoporosis, recurrent fractures and extraskeletal manifestations.MethodsA 56-year-old Indian woman presented to the clinic with complaints of difficulty in walking, recurrent fractures, limb bending, progressive skeletal deformities, and poor overall health. At the age of 37, she had experienced severe anemia with diarrhea, significant weight loss, knuckle pigmentation, and a significant loss of scalp hair. She had received multiple blood transfusions and parenteral iron supplementation with normalization of hemoglobin. Subsequently, she had premature menopause at the age of 37. She died at the age of 61 due to liver failure. Exome sequencing followed by Sanger sequencing were undertaken to identify the potential pathogenic mutations.ResultsGenetic investigation identified likely pathogenic mutations in the LRP5 and LGR4 genes. Out of the two mutations, the heterozygous mutation (c.1199C>T) in the LRP5 gene resulted in a non-synonymous substitution of alanine with valine at the 400th position, and the second mutation (c.1403A>C) in the LGR4 gene led to a non-synonymous substitution of tyrosine with serine at the 468th residue of the protein. The minor allele frequencies of the c.1199C>T (LRP5) substitution in the 1000 genomes and IndiGenomes databases are 0.0003 and 0.001, while the c.1403A>C (LGR4) substitution has not been reported in these databases. Various in silico prediction tools suggested LGR4 mutation to be pathogenic and LRP5 mutation to be likely pathogenic.ConclusionHeterozygous mutations in the LRP5 and LGR4 genes had additive deteriorative effects on BMD, resulting in recurrent fractures and bone deformities, and extended the effect to extraskeletal sites, contributing to the poor overall health in this patient.

Adeno-Associated Virus Gene Transfer Ameliorates Progression of Skeletal Lesions in Mucopolysaccharidosis IVA Mice.

Mucopolysaccharidosis type IVA (MPS IVA) is an autosomal congenital metabolic lysosomal disease caused by a deficiency of the N-acetyl-galactosamine-6-sulfate sulfatase (GALNS) gene, leading to severe skeletal dysplasia. The available therapeutics for patients with MPS IVA, enzyme replacement therapy and hematopoietic stem cell transplantation, revealed limitations in the impact of skeletal lesions. Our previous study, a significant leap forward in MPS IVA research, showed that liver-targeted adeno-associated virus (AAV) gene transfer of human GALNS (hGALNS) restored GALNS enzymatic activity in blood and multiple tissues and partially improved the aberrant accumulation of storage materials. This promising approach was further validated in our current study, where we delivered AAV8 vectors expressing hGALNS, under the control of a liver-specific or ubiquitous promoter, into MPS IVA murine disease models. The results were highly encouraging, with both AAV8 vectors leading to supraphysiological enzymatic activity in plasma and improved cytoplasmic vacuolization of chondrocytes in bone lesions of MPS IVA mice. Notably, the ubiquitous promoter constructs, a potential game-changer, resulted in significantly greater enzyme activity levels in bone and improved pathological findings of cartilage lesions in these mice than in a liver-specific one during the 12-week monitoring period, reinforcing the positive outcomes of our research in MPS IVA treatment.

Open reduction and plate fixation of fractures of both bones in the forearm in Klippel-Trenaunay-Weber syndrome: a case report

Klippel-Trenaunay-Weber syndrome (KTWS) is a rare disease characterized by vascular malformations, port-wine staining, and soft tissue and bone hypertrophy. Lesions occur in the lower extremities in 95% of cases, whereas only 5% occur in the upper extremities. Several case reports have described the treatment of fractures in the lower extremities in patients with KTWS. However, the risk of massive bleeding, bone deformity, and poor bone quality can lead to suboptimal surgical outcomes. No reports describing the treatment of forearm shaft fractures in KTWS could be found in the English-language literature. Intramedullary nailing is difficult due to the deformed bone and the risk of nonunion. Open reduction and internal fixation (ORIF) should be considered with caution in KTWS patients due to the risks of intraoperative bleeding and wound problems. The authors report that satisfactory results were obtained with ORIF after preoperative vascular embolization in a 60-year-old KTWS patient with fractures in both bones of the forearm.

Lentiviral Vector-Mediated Ex Vivo Hematopoietic Stem Cell Gene Therapy for Mucopolysaccharidosis IVA Murine Model.

Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive disease caused by a mutation in the N-acetylgalactosamine-6-sulfate-sulfatase (GALNS) gene resulting in progressive systemic skeletal dysplasia. There is currently no effective treatment available for this skeletal condition. Thus, the development of a new therapy stands as an unmet challenge in reversing or alleviating the progression of the disease. Our research, which could be a game-changer, hypothesizes that ex vivo lentiviral (LV) gene therapy (GT) could produce the supraphysiological level of active GALNS enzyme by hematopoietic stem cells (HSCs) transduced with LVs carrying the native GALNS gene under two different promoters (CBh and COL2A1), impacting bone and cartilage abnormalities in MPS IVA. We conditioned newborn knock-out (Galns-/-) MPS IVA mice with busulfan and intravenously transplanted LV-modified HSCs isolated from the bone marrow of Galns-/- donor mice. Transplanted mice were autopsied at 16 weeks, and tissues were collected to assess the therapeutic efficacy of modified HSCs in MPS IVA mice. Although HSC-LV-CBh-hGALNS provided a higher GALNS enzyme activity in plasma, HSC-LV-COL2A1-hGALNS stably corrected heart and bone abnormalities better under a low level of GALNS enzyme. Our findings suggest that ex vivo LV-GT may potentially treat MPS IVA.

The Spondylocarpotarsal Synostosis Syndrome Case with Ventricular Septal Defect Caused by a Homozygous Frameshift Variation in FLNB

AbstractSpondylocarpotarsal synostosis syndrome (SCT) (OMIM: 272460), an autosomal recessive disorder, is characterized by block vertebrae, carpal–tarsal synostosis, and disproportionate short stature. The clinical features of SCT include dysmorphic facial traits, cleft palate, hypoplastic tooth enamel, brachydactyly, clinodactyly, limited joint movement, and mixed hearing loss. SCT is associated with biallelic nonsense and frameshift pathogenic variants in the FLNB gene. An 8-year-old patient was referred with suspected skeletal dysplasia. The patient presented with short stature, scoliosis, carpal–tarsal synostosis, and ventricular septal defect (VSD). Clinical exome sequence analysis revealed a homozygous frameshift variation in the FLNB gene (c.219_222dup p.Met75Profs*17). No other pathogenic variations in genes related to VSD were found. This study aims to discuss novel clinical findings related to the genotype–phenotype association. To the best of our knowledge, this is the first reported case of SCT with VSD.

Bone impairment in atypical hemolytic and uremic syndrome treated by long-term eculizumab.

Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy, related to complement dysregulation, including Factor H deficiency (FH) treated by lifelong eculizumab therapy. Its long-term tolerance is not yet fully described. We report two patients with genetic FH deficiency receiving long-term eculizumab and displaying a peculiar bone phenotype. First case is a 13-year-old girl, presenting with bone pains, arthritis, and deformities, for which X-rays and MRI described multifocal osteochondritis. Bone biopsy revealed an active remodeling bone (many areas of bone formation and resorption) and C3c accumulation on immunohistochemical staining. The second patient is an 11-year-oldgirl, displaying mechanical bone pains, for which bone scintigraphy found hypofixation of wrists and ankles. These findings could be consistent with a side effect of eculizumab, as C3c accumulation may result from the downstream C5-blockade. Alternatively, bone alterations could be due to the absence of FH, as described in murine models. Further investigations are required to characterize bone disease in aHUS.

A novel frameshift deletion variant of ARSL associated with X-linked recessive chondrodysplasia punctata 1: a case report and literature review of prenatal, confirmed cases

BackgroundX-linked recessive chondrodysplasia punctata 1 (CDPX1) is a rare congenital skeletal dysplasia characterized by stippled epiphyses, nasal hypoplasia, and brachytelephalangy. ARSL (formerly known as ARSE), a member of the sulfatase gene family located on Xp22.3, has been identified as the causative gene for CDPX1. The high clinical and genetic heterogeneity of CDPX1 presents a challenge to prenatal diagnosis.Case presentationA G1P0 woman in her 30s with an unremarkable prenatal course presented in the second trimester. Maternal diseases, tobacco, alcohol, and drug history during pregnancy were denied. Obstetrical ultrasound examination revealed a flattened nose and a flattened midface with echogenic alterations of lumbar spinous process in the fetus. Amniocentesis was performed for genetic testing. A normal karyotype and a negative result of CNV-seq were obtained. However, Whole exome sequencing (WES) in trios revealed a hemizygous ARSL variant [NM_000047.3:c.1108del p.(Trp370Glyfs*35)] in the fetus, which was maternally inherited as confirmed by Sanger sequencing. This variant was absent from the genomAD and HGMD databases. According to the ACMG guidelines, this variant was interpreted as likely pathogenic (PVS1 + PM2_Supporting). The couple decided to terminate the pregnancy. After induction of labour, a severe nasal hypoplasia was noted; and brachytelephalangy was not remarkable. Postmortem digital X-ray imaging revealed symmetrical stippled epiphyses of the vertebrae in all spine regions and enlargement of spinous process of L1-L4 vertebrae.ConclusionA novel frameshift deletion variant of ARSL and the associated fetal phenotype have been identified. This study provides useful information for prenatal diagnosis and genetic counseling of CDPX1.

Comparative analysis of alveolar bone volume reconstruction outcomes using the guided bone regeneration technique

Relevance. The success of dental implant treatment in cases of reduced alveolar bone volume hinges on restoring bone to the required dimensions in each case. The guided bone regeneration (GBR) technique, which encompasses various techniques, holds a central role in oral reconstructive surgery and dental implantology due to its capacity for continuous improvement. The authors' experience with a modified GBR technique incorporating a situational Vicryl framework (SVF) has demonstrated enhanced effectiveness, with the potential to restore vertical bone volume by 5 mm or more. This study aimed to evaluate the advantages of the modified GBR technique using SVF compared to the conventional GBR technique.Materials and methods. This study is based on a comprehensive comparative analysis of two datasets: a retrospective evaluation of dental implant treatment outcomes in 210 patients who required alveolar bone volume restoration using the classical GBR technique, and clinical data from 40 patients treated with both the classical GBR technique and the proposed modified SVF technique The oral status of 40 patients included in the clinical analysis was characterized by partial edentulism, accompanied by mild to moderate alveolar bone deformities resulting from either inflammatory resorption or natural atrophy. The retrospective group 1 (comparisons) consisted of archival data of 210 patients. Retrospective data from 210 patients and clinical data from 40 patients were subjected to statistical analysis using parametric and non-parametric methods with IBM SPSS Statistics software.Results. A comprehensive comparative analysis of retrospective and clinical data revealed the following results. The value of the integrated "restored bone volume" parameter after vertical reconstruction in group 1 was 2-3 mm. The mean value of the integrated "restored bone volume" parameter after vertical reconstruction in group 2 was 3.20±0.96 mm, while in group 3, it was 4.60±1.63 mm for patients of both sexes. Comparison of the integrated "baseline deformation" parameter by technique showed a median deformation of 2.95 mm in group 2, treated with the classical GBR technique, and 4.95 mm in group 3, treated with the modified SVF technique. Similarly, the integrated "restored bone volume" parameter showed a median value of 2.95 mm in group 2 and 4.85 mm in group 3. The average value of the integrated "restored bone volume" parameter in group 2 was comparable to retrospective data from 210 patients in group 1.Conclusion. The comprehensive analysis of alveolar bone volume reconstruction using two GBR techniques, based on "baseline deformation" and "restored bone volume" parameters, demonstrated a significant advantage of the modified GBR technique compared to the classical technique.

Dwarfism-related skeletal dysplasia in Italy. Multi-analytic study of 8th century CE human remains from Azzio (Varese) and biocultural implications of a pathology

Skeletal dysplasias are a broad family of genetic disorders, often challenging to diagnose even in clinical literature without molecular analysis. Some cases of possible skeletal dysplasia have also been identified in osteoarchaeological samples, although achieving a definitive diagnosis is fraught with difficulties. This paper presents the analysis of the osteological remains of AZ-III-3, discovered in the archaeological context of the Church of Sant’Antonio and Eusebio in Azzio (Varese province, Italy). The study aims to demonstrate that even with limited skeletal elements, a diagnosis can be hypothesised using macroscopic morphometric and radio diagnostic techniques. These methods, compared with clinical and paleopathological literature, have allowed for the identification of a rare Italian case of dwarfism-related skeletal dysplasia. This contribution seeks to address the biocultural presence of individuals affected by these skeletal dysplasias, listing and discussing all published Italian cases, including that of AZ-III-3, whose chronological framework was established through both archaeological context analysis and 14C dating.

Biomechanical evaluation of six zygomatic implants versus four zygomatic implants combined with dental implants in the treatment of different maxillary defects

BackgroundThis study aims to compare the biomechanics of six zygomatic implants (ZIs) and dental implants (DIs) combined with four ZIs with different maxilla defects.MethodsThree-dimensional constructs of the ZIs, DIs human skulls, and maxillary prostheses were created using SolidWorks Software (Version 2015, Dassault Systems SolidWorks Corporation, Waltham, MA, USA). Eight finite element models of the skull with four different alveolar defect types (0–4) were constructed. Type 0: No defect; Type 1: Bilateral posterior defects; Type 2: Right posterior defect; Type 3: Anterior and left posterior defects; Type 4: Bilateral posterior and anterior defects. In two models with the same defect type (for defect types 0–2), six ZIs or two DIs combined with four ZIs were inserted into the maxilla. Six ZIs were inserted in the maxilla models with defect types 3 and 4. Vertical (150 N) and masseteric (300 N) loads were simulated on the prosthesis. The maximum Von Mises stress in the implants/surrounding bone and bone deformation were evaluated.ResultsThe maximum Von Mises stresses in bone/implant were found highest in the defect type 2 model with four ZIs combined with two DIs. The lowest maximum Von Mises stress for bone was detected in the model with defect type 0 and with six ZIs.ConclusionAmong the four types of defects, the posterior unilateral defect caused the highest stress value.

A monoallelic variant in CCN2 causes an autosomal dominant spondyloepimetaphyseal dysplasia with low bone mass

Cellular communication network factor 2 (CCN2) is a secreted extracellular matrix-associated protein, and its aberrantly increased expression has been implicated in a diversity of diseases involving pathological processes of fibrosis, chronic inflammation, or tissue injury, which has promoted the evaluation of CCN2 as therapeutic targets for multiple disorders. However, human phenotypes associated with CCN2 deficiency have remained enigmatic; variants in CCN2 have not yet been associated with a human phenotype. Here, we collected families diagnosed with spondyloepimetaphyseal dysplasia (SEMD), and screened candidate pathogenic genes for families without known genetic causes using next-generation sequencing. We identified a monoallelic variant in signal peptide of CCN2 (NM_001901.2: c.65 G > C [p.Arg22Pro]) as the cause of SEMD in 14 subjects presenting with different degree of short stature, premature osteoarthritis, and osteoporosis. Affected subjects showed decreased serum CCN2 levels. Cell lines harboring the variant displayed decreased amount of CCN2 proteins in culture medium and an increased intracellular retention, indicating impaired protein secretion. And the variant weakened the stimulation effect of CCN2 on osteogenesis of bone marrow mesenchymal stem cells. Zebrafish ccn2a knockout model and osteoblast lineage-specific Ccn2-deficient mice (Ccn2fl/fl;Prx1Cre) partially recapitulated the phenotypes including low bone mass observed in affected subjects. Pathological mechanism implicated in the skeletal abnormality in Ccn2fl/fl;Prx1Cre mice involved decreased bone formation, increased bone resorption, and abnormal growth plate formation. Collectively, our study indicate that monoallelic variants in CCN2 lead to a human inherited skeletal dysplasia, and highlight the critical role of CCN2 in osteogenesis in human.

Challenges of Hip and Knee Arthroplasty in Patients With Osteopetrosis.

Osteopetrosis is a rare metabolic bone disease, characterized by dysfunction of osteoclasts, resulting in increased bone density and brittleness leading to pathological fractures and bone deformities. Hip and knee osteoarthritis (OA) are common long-term complications in patients with osteopetrosis. Joint arthroplasty surgery remains an effective and recommended treatment for these patients with an end-stage OA because it provides favorable outcomes. However, in osteopetrosis, joint arthroplasty surgery carries an increased risk of complications, and specific preoperative and perioperative considerations are required to deal with the technical challenges related to the disease. The aim of this article was to review some of the key aspects of osteopetrosis, provide technical recommendations, and answer clinically relevant questions related to hip and knee arthroplasty surgery.

Long-Term Outcomes of Airway Management in 6 Children With Campomelic Dysplasia.

This case series describes the outcomes of airway management, including airway reconstruction, in 6 patients with campomelic dysplasia and tracheostomy/ventilator dependence secondary to multilevel airway obstruction. Case series and clinical guidelines are provided for the airway management of patients with campomelic dysplasia. Average age of individuals is 19.4 years. Mean follow-up was 12.2 years. Four individuals underwent open airway reconstruction and achieved decannulation. One patient underwent airway reconstruction with improvement of a complete subglottic stenosis but remains ventilator dependent due to severe scoliosis. The remaining 2 patients did not require additional airway reconstruction, have been liberated from ventilator support, and are under evaluation for tracheostomy tube decannulation. Although campomelic dysplasia was historically considered a lethal form of congenital skeletal dysplasia, with many patients succumbing to respiratory failure due to tracheobronchomalacia in the neonatal period, airway reconstruction and long-term survivorship is feasible in children with campomelic dysplasia and significant airway disease.

Identification of LRP1+CD13+ human periosteal stem cells that require LRP1 for bone repair.

Human periosteal skeletal stem cells (P-SSCs) are critical for cortical bone maintenance and repair. However, their in vivo identity, molecular characteristics, and specific markers remain unknown. Here, single-cell sequencing revealed human periosteum contains SSC clusters expressing known SSC markers, PDPN and PDGFRA. Notably, human P-SSCs, but not bone marrow SSCs (BM-SSCs), selectively expressed newly identified markers, LRP1 and CD13. These LRP1+CD13+ human P-SSCs were perivascular cells with high osteochondrogenic but minimal adipogenic potential. Upon transplantation into bone injuries in mice, they preserved self-renewal capability in vivo. Single-cell analysis of mouse periosteum further supported the preferential expression of LRP1 and CD13 in Prx1+ P-SSCs. When Lrp1 was conditionally deleted in Prx1-lineage cells, it led to severe bone deformity, short statue, and periosteal defects. By contrast, local treatment with a LRP1 agonist at the injury sites induced early P-SSC proliferation and bone healing. Thus, human and mouse periosteum contains unique osteochondrogenic stem cell subsets, and these P-SSCs express specific markers, LRP1 and CD13, with regulatory mechanism through LRP1 that enhances P-SSC function and bone repair.

Hematopoietic stem cell transplantation in children with mucopolysaccharidosis IVA: single center experience.

Mucopolysaccharidosis IVA (MPS IVA; Morquio syndrome) is a lysosomal storage disorder and features systemic skeletal dysplasia that is caused by defective Nacetylgalactosamine-6-sulfate sulfatase (GALNS). Although there are convincing data for hematopoietic stem cell transplantation (HSCT) in certain types of MPS, the studies are limited for MPS IVA and more data is still pending to show the efficacy/safety of HSCT. This study included 3 girls and 7 boys, with a median age of 75,5 months (35-186 months), who underwent allogeneic HSCT for severe MPS IVA between February 12, 2021, and March 10, 2023. Enzyme levels, height growth, the most involved organs (ear, eye, and heart), and the activities of daily living (ADL) scoring system were monitored to assess the benefit of HSCT. In a median follow-up of 20 months (9-34 months), there is no severe transplant-related adverse event was observed. In all cases, normal enzyme levels were reached after HSCT. During the short follow-up period, our cases showed an increase in stature and improvement in daily activity functions. Here we present the data of our HSCT experience in MPS IVA with promising results regarding both safety and efficacy. Although there are signs of amelioration with HSCT, we need more data and long-term follow-up to comment properly on the benefits of HSCT in MPS IVA.

Comparative Histopathological Analysis of Nasal Osteotomy Techniques in a Rabbit Model.

Objective: Nasal osteotomy is a crucial step in rhinoplasty, explicitly addressing the open roof deformity in nasal bones. This study aimed to assess and compare the recovery patterns associated with 4 distinct osteotomy techniques in a rabbit model. Materials and Methods: Twenty white New Zealand rabbits weighing 2.5 to 3.0 kg were included in the study. Median osteotomies were performed on the left side using piezosurgery and on the right side using an oscillating micro-saw. Additionally, internal osteotomy was executed on the right side and external osteotomy on the left side, both performed with a chisel across all rabbits. Ten rabbits were sacrificed on the 7th day, while the remaining 10 were sacrificed on the 15th day for subsequent histological examination. The granulation tissue formation (GTF), vascularization, inflammation, collagen fibril content, osteotomy gap width, and new bone formation were evaluated in hematoxylin and eosin and Masson's trichrome-stained sections. Results: On the 7th day, piezosurgery demonstrated statistically-significant advantages in terms of GTF, neovascularization, and collagen fibril quantity when compared to the oscillating micro-saw (P < .05). Furthermore, a statistically-significant difference was observed among the groups concerning the distribution of connective tissue organization between the 7th and 15th days (P < .05). Conclusions: This study's findings unequivocally establish that bone healing after osteotomy with piezosurgery surpasses that achieved with an oscillating micro-saw in this rabbit model.