Bone Formation Research Articles

ATAD2 Drives Prostate Cancer Progression to Metastasis.

Metastasis accounts for the overwhelming majority of cancer deaths. In prostate cancer and many other solid tumors, progression to metastasis is associated with drastically reduced survival outcomes, yet the mechanisms behind this progression remain largely unknown. ATAD2 (ATPase family AAA domain containing 2) is an epigenetic reader of acetylated histones that is overexpressed in multiple cancer types and usually associated with poor patient outcomes. However, the functional role of ATAD2 in cancer progression and metastasis has been relatively understudied. Here we employ genetically engineered mouse models of prostate cancer bone metastasis, as well as multiple independent human cohorts, to show that ATAD2 is highly enriched in bone metastasis compared to primary tumors and significantly associated with the development of metastasis. We show that ATAD2 expression is associated with MYC pathway activation in patient datasets and that, at least in a subset of tumors, MYC and ATAD2 can regulate each other's expression. Using functional studies on mouse bone metastatic cell lines and innovative organ-on-a-chip bone invasion assays, we establish a functional role for ATAD2 inhibition in diminishing prostate cancer metastasis and growth in bone. Implications: Our study highlights ATAD2 as a driver of prostate cancer progression and metastasis and suggests it may constitute a promising novel therapeutic target.

Chiral Supramolecular Hydrogels Regulating Both Osteoblastogenesis and Osteoclastogenesis

Osteoporosis, a chronic bone disorder, poses a global threat to the health of millions of individuals. The disruption of bone homeostasis is the fundamental cause of osteoporosis. Currently, clinical drugs are employed to promote bone formation via enhancing osteogenesis and/or reduce bone loss via inhibiting osteoclastogenesis. However, it is difficult for the current drugs to simultaneously address the osteoblastogenesis and osteoclastogenesis issues associated with osteoporosis. Hence, L/D-phenylalanine derivatives (L/DPF), combined with Mg2+ ions, are employed to assemble into chiral supramolecular hydrogels which facilitate osteocyte activity and inhibit osteoclast function. LPF_Mg hydrogels and DPF_Mg hydrogels demonstrate the opposite supramolecular chirality. Specifically, LPF_Mg hydrogels and DPF_Mg hydrogels are composed of left-handed (M-type) helical nanofibers and right-handed (P-type) helical nanofibers, respectively. The hydrogen bonding and π–π stacking interactions are crucial in the process of hydrogel formation. The chiral left-handed nanofibrous DPF_Mg hydrogels significantly promote osteogenic differentiation of MC3T3 cells and inhibit osteoclast differentiation of RAW267.4 cells, thereby demonstrating substantial potential for applications in improving skeletal health. These findings provide a promising novel perspective on the application of chiral functional materials for osteoporosis therapy.

Clinical efficacy and safety of P-15 peptide enhanced bone graft substitute in surgical bone regenerative procedures in adult maxillofacial, spine, and trauma patients : a systematic literature review.

Autologous bone graft (ABG) is considered the 'gold standard' among graft materials for bone regeneration. However, complications including limited availability, donor site morbidity, and deterioration of regenerative capacity over time have been reported. P-15 is a synthetic peptide that mimics the cell binding domain of Type-I collagen. This peptide stimulates new bone formation by enhancing osteogenic cell attachment, proliferation, and differentiation. The objective of this study was to conduct a systematic literature review to determine the clinical efficacy and safety of P-15 peptide in bone regeneration throughout the skeletal system. PubMed, Embase, Web of Science, and Cochrane Library were searched for relevant articles on 13 May 2023. The systematic review was reported according to the PRISMA guidelines. Two reviewers independently screened and assessed the identified articles. Quality assessment was conducted using the methodological index for non-randomized studies and the risk of bias assessment tool for randomized controlled trials. After screening, 28 articles were included and grouped by surgical indication, e.g. maxillofacial procedures (n = 18), spine (n = 9), and trauma (n = 1). Published results showed that P-15 peptide was effective in spinal fusion (n = 7) and maxillofacial (n = 11), with very few clinically relevant adverse events related to P-15 peptide. This systematic literature review concluded that moderate- (risk of bias, some concern: 50%) to high-quality (risk of bias, low: 46%) clinical evidence exists showing equivalent safety and efficacy in bone regeneration using a P-15 peptide enhanced bone graft substitute compared to ABG. P-15 peptide is safe and effective, resulting in rapid bone formation with a low probability of minor complications.

Immune cell profiles and predictive modeling in osteoporotic vertebral fractures using XGBoost machine learning algorithms.

Osteoporosis significantly increases the risk of vertebral fractures, particularly among postmenopausal women, decreasing their quality of life. These fractures, often undiagnosed, can lead to severe health consequences and are influenced by bone mineral density and abnormal loads. Management strategies range from non-surgical interventions to surgical treatments. Moreover, the interaction between immune cells and bone cells plays a crucial role in bone repair processes, highlighting the importance of osteoimmunology in understanding and treating bone pathologies. This study aims to investigate the xCell signature-based immune cell profiles in osteoporotic patients with and without vertebral fractures, utilizing advanced predictive modeling through the XGBoost algorithm. Our findings reveal an increased presence of CD4 + naïve T cells and central memory T cells in VF patients, indicating distinct adaptive immune responses. The XGBoost model identified Th1 cells, CD4 memory T cells, and hematopoietic stem cells as key predictors of VF. Notably, VF patients exhibited a reduction in Th1 cells and an enrichment of Th17 cells, which promote osteoclastogenesis and bone resorption. Gene expression analysis further highlighted an upregulation of osteoclast-related genes and a downregulation of osteoblast-related genes in VF patients, emphasizing the disrupted balance between bone formation and resorption. These findings underscore the critical role of immune cells in the pathogenesis of osteoporotic fractures and highlight the potential of XGBoost in identifying key biomarkers and therapeutic targets for mitigating fracture risk in osteoporotic patients.

Application and progress of 3D printed biomaterials in osteoporosis

Osteoporosis results from a disruption in skeletal homeostasis caused by an imbalance between bone resorption and bone formation. Conventional treatments, such as pharmaceutical drugs and hormone replacement therapy, often yield suboptimal results and are frequently associated with side effects. Recently, biomaterial-based approaches have gained attention as promising alternatives for managing osteoporosis. This review summarizes the current advancements in 3D-printed biomaterials designed for osteoporosis treatment. The benefits of biomaterial-based approaches compared to traditional systemic drug therapies are discussed. These 3D-printed materials can be broadly categorized based on their functionalities, including promoting osteogenesis, reducing inflammation, exhibiting antioxidant properties, and inhibiting osteoclast activity. 3D printing has the advantages of speed, precision, personalization, etc. It is able to satisfy the requirements of irregular geometry, differentiated composition, and multilayered structure of articular osteochondral scaffolds with boundary layer structure. The limitations of existing biomaterials are critically analyzed and future directions for biomaterial-based therapies are considered.

Wnt signaling as a translational target in rheumatoid and psoriatic arthritis.

Rheumatoid arthritis (RA) and Psoriatic arthritis (PsA) are chronic inflammatory diseases mainly affecting joints. RA primarily targets the synovial joints and is characterized by cartilage and bone erosion, whereas PsA is associated with skin and nail psoriasis and is characterized by erosive bone damage with an exuberant bone formation and soft tissue involvement. Recent evidence described the involvement of the Wnt pathway in the pathogenesis of these diseases. Thus, we aimed to analyze some components of Wnt signaling, i.e. DKK1, Wnt 5a and β-catenin, and their association with disease activity indices, investigating possible differences between the two diseases. Sera from 18 RA patients naïve for biological therapy, 18 PsA patients and 20 matched healthy donors (HD) were tested for DKK1 by ELISA, Wnt 5a and β-catenin by Immunoblotting. Values were correlated with CTX-1, detected by ELISA, and with disease activity indices: Disease Activity Score on 28 joints (DAS28-CRP) for RA and the Disease Activity in Psoriatic Arthritis (DAPSA) score for PsA. This study highlights significant increase in DKK1, Wnt 5a, and β-catenin levels in RA and PsA patients compared to HD, with distinct patterns of correlation with disease activity indices. Indeed, in RA patients, DKK1 levels positively correlated with DAS28-CRP score, whereas in PsA patients, DKK1 levels negatively correlated with DAPSA score. Our findings showed a strong correlation between DKK1 and CTX-1 levels in RA patients, supporting the relationship between DKK1 levels and the presence of joint erosions. Furthermore, a significant positive correlation was found between β-catenin and IL-6 levels in RA, indicating that β-catenin may be involved in the inflammatory cascade. This study compares the involvement of Wnt signaling in RA and PsA, suggesting that Wnt signaling may represent a possible mechanism of disease activity. In particular, it indicates that DKK1 levels are correlated with CTX-1, a marker of bone resorption, and with disease activity in RA patients. These findings underscore the importance of these biomarkers in the potential monitoring of patients, offering insights into disease mechanisms and potential therapeutic targets.

Astaxanthin Prevents Glucocorticoid-Induced Femoral Head Osteonecrosis by Targeting Ferroptosis through the JAK2/STAT3 Signaling Pathway.

Glucocorticoid (GC) is extensively used in clinical practice, and the osteonecrosis of the femoral head caused by them is a common issue in orthopedic surgery, yet the underlying mechanisms remain unclear. Astaxanthin (AST), a potent natural antioxidant, has an unexplored impact on GC-induced osteonecrosis of the femoral head (GIONFH). This study explores the effects and mechanisms of AST in counteracting dexamethasone (Dex)-induced ferroptosis and GIONFH. We developed a rat model of GIONFH using intraperitoneal Dex injections and conducted in vitro analysis by culturing osteoblasts (OBs) with Dex treatment. We assessed the impact of AST on Dex-treated OBs using C11-BODIPY and FerroOrange staining, mitochondrial functionality tests, and protein expression analyses through Western blot and immunofluorescence. The influence of AST on bone microarchitecture of femoral head in rat was assessed using micro-CT, hematoxylin and eosin staining, immunofluorescence, and immunohistochemistry at imaging and histological levels. Our findings suggest that AST exerts an inhibitory effect on Dex-induced ferroptosis and GIONFH. In vitro, AST treatment increased glutathione and decreased malondialdehyde, lipid peroxidation, and mitochondrial-reactive oxygen species. Additionally, AST treatment also enhances the phosphorylation of STAT3, upregulates glutathione peroxidase 4 and osteogenic-related proteins, and stimulates bone formation. To delve deeper into the mechanism, the findings revealed that AST triggered activation of JAK2/STAT3 signaling. Moreover, the use of siRNA-STAT3 blocked the beneficial effect of AST in OBs cultivated with Dex. In brief, AST combats GIONFH by activating the JAK2/STAT3 pathway to inhibit ferroptosis.

Age-specific over-the-top techniques for physeal sparing anterior cruciate ligament (ACL) reconstruction in skeletally immature patients: Current concepts for prepubescents to older adolescents.

Tailored surgical strategies for anterior cruciate ligament (ACL) reconstruction in skeletally immature patients are presented, emphasizing techniques to minimize growth plate damage and ensure stability. As ACL injuries in youth increase, delaying surgery can lead to joint damage and poor recovery outcomes. Using magnetic resonance imaging-based assessments of skeletal maturity, the authors propose the 'over-the-top (OTT)' approach with lateral tenodesis, adapted for three growth stages: prepubescents, young adolescents and older adolescents. For prepubescents, the extra-physeal approach avoids growth plate drilling; for young adolescents, the supra-physeal technique places tunnels above the growth plate; and for older adolescents, the trans-physeal method mirrors adult techniques, as growth plates are closing. The minimally invasive OTT technique preserves hamstring insertion, ensures isometric graft placement, and allows for combined intra- and extra-articular procedures to improve rotational control and protect the graft. Clinical outcomes highlight high return-to-sport rates, minimal growth disturbances, and low failure rates, although older adolescents show higher graft failures due to activity levels. Various adaptations of the OTT and lateral tenodesis techniques utilizing hamstring tendons provide promising solutions for addressing ACL injuries in skeletally immature patients, ranging from prepubescence to late adolescence. Assessing skeletal age and estimating remaining bone growth are essential for selecting the most appropriate surgical method. The biomechanical principles and positive clinical results observed across different patient groups highlight these techniques as effective, safe and attractive options for managing these challenging cases. LEVEL OF EVIDENCE: Level IV.

Bone fusion materials: past, present, and future.

Bone fusion is one of the mainstay managements for degenerative spinal diseases and critical-sized bone defects resulting from trauma, tumors, infection, and nonunion. Bone graft materials are required for promoting bone healing, with autografts historically considered the gold standard due to their osteogenic, osteoinductive, and osteoconductive properties. However, donor site morbidities have led to the development of alternative bone graft substitutes. Currently available alternative options for bone fusion include allografts, ceramics, demineralized bone matrix (DBM), and bone morphogenetic proteins (BMPs). Each material has its advantages and disadvantages. Allografts avoid donor site morbidities but lack osteogenic properties and pose disease transmission risks. DBMs are acid-extracted allografts that have osteoconductive and osteoinductive properties but require combination with autografts because of the lack of evidence for their stand-alone use. BMP-2 has potent osteoinductive properties and is considered an ideal fusion material, but faces unresolved challenges related to optimal dosage and carrier. Synthetic peptides, mimicking the cell-binding domain of type I collagen, facilitate the attachment of osteogenic cells (such as osteoblasts) to the graft material and the production of extracellular matrix, leading to improved bone growth at the fusion site. The development of materials with ideal properties is a research hotspot. Recent advancements in biomaterials, such as hydrogels, nanomaterials, and three-dimensional-printed biomaterials, offer promising future options for bone fusion. This review provides an overview of available bone fusion materials, their advantages and disadvantages, and introduces emerging candidate options for bone fusion.

Growth hormone signaling and clinical implications: from molecular to therapeutic perspectives.

Growth hormone (GH) is a key polypeptide hormone secreted by somatotroph cells in the anterior pituitary gland, essential for postnatal growth, metabolism, and systemic homeostasis. Its secretion is regulated by hypothalamic neuropeptides, including GH-releasing hormone and somatostatin. GH exerts effects through direct interaction with the growth hormone receptor and indirect pathways mediated by the GH-IGF-I axis. GHR activation triggers signaling pathways, such as JAK-STAT, PI3K/AKT, and MAPK, promoting cellular proliferation, differentiation, and metabolic balance. The GH-IGF-I axis is critical for bone growth, lipid and carbohydrate metabolism, and organ-specific physiological functions. Dysregulation of GH results in diverse disorders. Congenital deficiencies, like isolated GH deficiency and syndromic conditions (e.g., Turner syndrome), stem from genetic mutations. Acquired deficiencies arise from trauma, tumors, infections, or autoimmune damage, while GH overproduction causes gigantism in children and acromegaly in adults, often due to pituitary adenomas. Idiopathic deficiencies, lacking identifiable causes, complicate management further. Advances in therapy have transformed outcomes for GH disorders. Recombinant human growth hormone provides effective replacement therapy for deficiencies. Somatostatin analogs, dopamine receptor agonists, and GH receptor antagonists are pivotal for managing GH excess. Surgical and radiotherapeutic interventions remain essential for pituitary adenomas. However, GH therapy requires close monitoring to prevent side effects like insulin resistance and metabolic complications. This review provides a comprehensive evaluation of the molecular mechanisms underlying GH action, its physiological roles, GH-related disorders, and therapeutic approaches to optimize patient outcomes.

Interruption of mitochondrial symbiosis is associated with the development of osteoporosis

Mitochondria maintain bacterial traits because of their endosymbiotic origins, yet the host cell recognizes them as non-threatening since the organelles are compartmentalized. Nevertheless, the controlled release of mitochondrial components into the cytoplasm can initiate cell death, activate innate immunity, and provoke inflammation. This selective interruption of endosymbiosis as early as 2 billion years ago allowed mitochondria to become intracellular signaling hubs. Recent studies have found that the interruption of mitochondrial symbiosis may be closely related to the occurrence of various diseases, especially osteoporosis (OP). OP is a systemic bone disease characterized by reduced bone mass, impaired bone microstructure, elevated bone fragility, and susceptibility to fracture. The interruption of intra-mitochondrial symbiosis affects the energy metabolism of bone cells, leads to the imbalance of bone formation and bone absorption, and promotes the occurrence of osteoporosis. In this paper, we reviewed the mechanism of mitochondrial intersymbiosis interruption in OP, discussed the relationship between mitochondrial intersymbiosis interruption and bone marrow mesenchymal stem cells, osteoblasts and osteoclasts, as well as the inheritance and adaptation in the evolutionary process, and prospected the future research direction to provide new ideas for clinical treatment.

Fibrous Dysplasia: From Historical Approaches to Modern Treatment Perspectives

Objective. This study aims to analyze scientific literature on fibrous dysplasia (FD) and highlight the state of diagnosis and treatment of orthopedic pathology in patients with various forms of FD. Materials and Methods. This article is based on a retrospective review of papers by various authors on the treatment of patients with FD. Articles were selected from scientific databases such as SCOPUS, Web of Science, and Google Scholar. The selected articles were reviewed in chronological order according to the topic of the study. Results and Discussion. The article provides a systematic analysis of treatment approaches for patients with FD at different stages of the development of science. Modern diagnostic and therapeutic approaches are also analyzed, with particular attention given to the molecular-genetic aspects of the disease’s etiology, particularly mutations in the GNAS gene, which underlie bone growth regulation disorders. Current treatment approaches, including the use of bisphosphonates and various types of surgical interventions, are discussed. Conclusions. A review of the scientific literature and analysis of historical aspects related to FD indicate both significant achievements of the orthopedic community in the diagnosis and treatment of FD, as well as significant challenges that will require further resolution. Changing views on the etiology and pathogenesis of the disease, as well as the identification of genetic mutations during early fetal development, have led to the recognition of FD as a stem cell disease. This provides new leverage for doctors and researchers to use stem cells in the treatment of patients with this pathology. Research on FD and the identification of this pathology as a result of stem cell disease has allowed scientists to explore new therapeutic approaches based on the use of mesenchymal stem cells (MSCs). MSCs can be used to correct bone tissue disorders since they can differentiate into osteoblasts and promote bone tissue remodeling. This opens the possibility for MSC transplantation or modification of their functioning to restore bone structures affected by FD. In our opinion, one promising area is the study of the osteogenic activity of MSCs from pathological sites, as this may help develop new regeneration strategies. There is a limited number of studies indicating the potential for bone defect reconstruction through the combination of MSCs and allomaterial.

Effects of Exercise Speed and Circle Diameter on Markers of Bone and Joint Health in Juvenile Sheep as an Equine Model

Though circular exercise is commonly used in equestrian disciplines, it may be at the detriment of horses’ musculoskeletal system. To investigate the effects of circular exercise on bone and joint health, 42 lambs were randomly assigned to a non-exercised control, straight-line, small circle, or large circle exercise regime at a slow (1.3 m/s) or fast (2.0 m/s) speed for 12 wk. Blood samples were taken biweekly. Animals were humanely euthanized upon study completion, and the fused third and fourth metacarpals were collected for biomechanical testing and bone density analysis. Fast groups were found to have more bone formation and less resorption activity than slow groups as evidenced by serum biomarker concentrations (p < 0.05). Sheep in the large fast group tended to have greater flexural rigidity and fracture force for the outside leg compared to the inside leg (p < 0.1). Sheep in the small slow group tended to have increased bone mineral density of the outside leg compared to the inside leg, whereas the opposite occurred in the large slow group (p < 0.1). These results provide further evidence for potential asymmetric musculoskeletal adaptations to circular exercise while emphasizing the importance of speed as a positive influence on bone metabolism and strength.

Biological, Biomechanical, and Histopathological Evaluation of Polyetherketoneketone Bioactive Composite as Implant Material.

While polyetherketoneketone is a high-performance thermoplastic polymer, its hydrophobicity and inertness limit bone adhesion. This study aimed to evaluate a novel PEKK/CaSiO3/TeO2 nanocomposite, comparing it to PEKK/15 wt.% CaSiO3 and PEKK groups. The invitro study, involving 90 discs (n = 30), assessed the cytotoxicity of all groups after 24, 72, and 168 h. The invivo animal study, using cylinder-type implants (n = 30), evaluated osseointegration through biomechanical push-out tests, descriptive histopathological examinations of decalcified sections stained with hematoxylin and eosin, and histomorphometric analysis of new bone formation area after 2- and 6-week healing intervals. The cytocompatibility of PEKK/15 wt.% CaSiO3/1 wt.% TeO2 composite confirmed its acceptance as a biomedical material. Additionally, invivo study results showed that the PEKK/15 wt.% CaSiO3/1 wt.% TeO2 had the highest shear strength value and the highest new bone formation area compared to other experimental groups. The multimodal concept of adding CaSiO3 micro fillers and TeO2 nanofillers to PEKK produces a cytocompatible composite that enhances osseointegration and new bone formation in a rabbit's femur after 2- and 6-week healing intervals.

Advances in the application and research of biomaterials in promoting bone repair and regeneration through immune modulation.

With the ongoing development of osteoimmunology, increasing evidence indicates that the local immune microenvironment plays a critical role in various stages of bone formation. Consequently, modulating the immune inflammatory response triggered by biomaterials to foster a more favorable immune microenvironment for bone regeneration has emerged as a novel strategy in bone tissue engineering. This review first examines the roles of various immune cells in bone tissue injury and repair. Then, the contributions of different biomaterials, including metals, bioceramics, and polymers, in promoting osteogenesis through immune regulation, as well as their future development directions, are discussed. Finally, various design strategies, such as modifying the physicochemical properties of biomaterials and integrating bioactive substances, to optimize material design and create an immune environment conducive to bone formation, are explored. In summary, this review comprehensively covers strategies and approaches for promoting bone tissue regeneration through immune modulation. It offers a thorough understanding of current research trends in biomaterial-based immune regulation, serving as a theoretical reference for the further development and clinical application of biomaterials in bone tissue engineering.

What Doesn't Kill You Makes You Stronger? Examining Relationships Between Early-Life Stress, Later-Life Inflammation and Mortality Risk in Skeletal Remains.

This paper explores conflicting perspectives on the adaptive significance of phenotypic plasticity during fetal and early postnatal development and the impact that stressors experienced during this critical early-life period have on later-life morbidity and mortality risk. The sample (n = 216) comprised archeologically-recovered human skeletons. A geometric morphometric (GM) method was employed to evaluate first permanent molar (M1) fluctuating asymmetry (FA) and provide a proxy for early-life stress. Shifts in later-life physiology were inferred through two inflammatory lesions: periosteal new bone formation (PNBF) and periodontal disease (PD). To explore mortality risk, age-at-death was estimated through dental development for skeletally immature individuals (n = 104) and through senescent skeletal changes for mature skeletons (n = 112). Significant differences were found in M1 FA between groups, with the immature cohort associated with elevated FA. Within-group analysis revealed age-at-death in the immature group had a significant positive relationship with M1 FA and PD presence. In the mature group, alongside sex and the co-occurrence of PD and PNBF, FA was a significant predictor of a shorter life. Higher FA was also associated with active and bilaterally expressed PNBF. It is theorized that early-life stress, if survived, programmed a hyperinflammatory response to environmentally-mediated physiological perturbations which increased the chances of survival during subsequent development but also elevated later-life mortality risk. Findings demonstrate a complicated relationship between developmental stress and physiological shifts that helps to illustrate the adaptive significance of early-life programming and support the Thrifty Phenotype hypothesis.

Peptide platform for 3D-printed Ti implants with synergistic antibacterial and osteogenic functions to enhance osseointegration.

Bone defects caused by trauma, infection, or tumors present a major clinical challenge. Titanium (Ti) implants are widely used due to their excellent mechanical properties and biocompatibility; however, their high elastic modulus, low surface bioactivity, and susceptibility to infection hinder osseointegration and increase failure rates. There is an increasing demand for implants that can resist bacterial infection while promoting osseointegration. In this study, we developed a peptide platform to engineer a multifunctional 3D-printed Ti implant (3DTi) modified with a fusion peptide composed of minTBP-1 (targeting peptide), KR-12 (antibacterial peptide), and GFOGER (adhesion peptide), termed 3DTi-NFP. This design enables specific targeting, localized delivery, prevention of peptide release into circulation, and functional integrity through linker retention. In both in vitro and in vivo infected bone defect models, 3DTi-NFP implants demonstrated excellent biocompatibility and achieved over 90% bactericidal efficiency against S. aureus and E. coli. The implants reduced bacterial colonization while enhancing adhesion, proliferation, and differentiation of bone marrow mesenchymal stem cells (BMSCs), significantly upregulating osteogenic genes and protein expression. Transcriptome sequencing further explored the molecular mechanisms underlying the synergistic effects of 3DTi-NFP, revealing activation of the focal adhesion and PI3K-Akt signaling pathways-key contributors to cell adhesion, matrix formation, and new bone formation. Overall, this study provides a promising strategy to improve the long-term success of Ti-based implants, with significant potential for tissue regeneration and clinical applications.

Dual-functional improvement of vascularization and bone formation of complementary PRP-based gel scaffold

Dual-functional improvement of vascularization and bone formation of complementary PRP-based gel scaffold

Optimizing natural human-derived decellularized tissue materials for periodontal bone defect repair.

Periodontal disease is a major contributor to tooth loss worldwide in adults. Particularly, periodontal bone defect is a common clinical condition, yet current therapeutic strategies exhibit limited effectiveness. Recently, natural bone graft materials have attracted considerable interest for enhancing bone defect repair due to their superior biocompatibility and osteogenic capabilities. Nevertheless, clinically applicable human-derived biomaterials to boost bone regeneration are currently not accessible. Here, enlightened by the decellularization technique, we successfully prepared the human decellularized alveolar bone and tooth dentin tissues from healthy individuals and obtained micro-sized bioactive decellularized extracellular matrix (dECM) particles for treatment of periodontal bone defects. After characterizing the two representative dECM tissues and particles by multiple physiochemical approaches, we revealed that both human decellularized alveolar bone matrix particles (hDABMPs) and human decellularized tooth dentin matrix particles (hDTDMPs) possessed excellent biocompatibility. Furthermore, both biomaterials significantly enhanced the proliferation and osteogenic differentiation of human dental follicle stem cells, potentially contributing to periodontal bone formation. Indeed, in a rat model, both types of dECM microparticles were found to facilitate tissue regeneration at periodontal bone defect sites, demonstrating comparable efficacy for promoting bone defect repair. Collectively, this study provides an important basis for clinical exploration of natural human-derived micro-sized biomaterials for periodontal bone defect repair and opens a new path for periodontal disease treatment strategies.

Ossification of the Posterior Longitudinal Ligament in the Cervical Spine: Etiology, Clinical Presentation, and Management.

» Ossification of the posterior longitudinal ligament (OPLL) is a hyperostotic condition that results in ectopic bone formation and calcification of the posterior longitudinal ligament.» OPLL can present in any race/ethnicity but historically has been reported in the East Asian population.» OPLL predisposes patients to spinal cord injury in the setting of minor trauma.» Asymptomatic patients typically can be managed nonoperatively. Surgical treatment is reserved for patients presenting with myelopathy and worsening radiculopathy that has not responded to conservative treatment.» The decision to use anterior, posterior, or combined anterior-posterior approaches should be an individualized decision that considers the degree of OPLL pathology, K-line imaging findings, and other patient-specific risk factors.