Dual-functional Hydroxyapatite scaffolds for bone regeneration and precision drug delivery.

Addressing infected bone defects remains a significant challenge in orthopedics, requiring effective infection control and bone defect repair. A promising therapeutic approach involves the development of dual-functional engineered biomaterials with drug delivery systems that combine antibacterial properties with osteogenesis promotion. The Hydroxyapatite composite scaffolds offer a one-stage treatment, eliminating the need for multiple surgeries and thereby streamlining the process and reducing treatment time. This review delves into the impaired bone repair mechanisms within pathogen-infected and inflamed microenvironments, providing a theoretical foundation for treating infectious bone defects. Additionally, it explores composite scaffolds made of antibacterial and osteogenic materials, along with advanced drug delivery systems that possess both antibacterial and bone-regenerative properties. By offering a comprehensive understanding of the microenvironment of infectious bone defects and innovative design strategies for dual-function scaffolds, this review presents significant advancements in treatment methods for infectious bone defects. Continued research and clinical validation are essential to refine these innovations, ensuring biocompatibility and safety, achieving controlled release and stability, and developing scalable manufacturing processes for widespread clinical application.

Antibacterial sequential growth factor delivery from alginate/gelatin methacryloyl microspheres for bone regeneration.

Autologous or allogeneic bone tissue grafts remain the mainstay of treatment for clinical bone defects. However, the risk of infection and donor scarcity in bone grafting pose challenges to the process. Therefore, the development of excellent biomaterial grafts is of great clinical importance for the repair of bone defects. In this study, we used gas-assisted microfluidics to construct double-cross-linked hydrogel microspheres with good biological function based on the ionic cross-linking of Cu2+ with alginate and photo-cross-linking of gelatin methacryloylamide (GelMA) by loading vascular endothelial growth factor (VEGF) and His-tagged bone morphogenetic protein-2 (BMP2) (AGMP@VEGF&BMP2). The Cu2+ component in the microspheres showed good antibacterial and drug-release behavior, whereas VEGF and BMP2 effectively promoted angiogenesis and bone tissue repair. In in vitro and in vivo experiments, the dual cross-linked hydrogel microspheres showed good biological function and biocompatibility. These results demonstrate that AGMP@VEGF&BMP2 microspheres could be used as a bone defect graft substitute to promote effective healing of bone defects and may be applied to other tissue engineering studies.

3D-printed bone regeneration scaffolds modulate bone metabolic homeostasis through vascularization for osteoporotic bone defects.

The treatment of osteoporotic bone defects poses a challenge due to the degradation of the skeletal vascular system and the disruption of local bone metabolism within the osteoporotic microenvironment. However, it is feasible to modulate the disrupted local bone metabolism imbalance through enhanced vascularization, a theory termed "vascularization-bone metabolic balance". This study developed a 3D-printed polycaprolactone (PCL) scaffold modified with EPLQLKM and SVVYGLR peptides (PCL-SE). The EPLQLKM peptide attracts bone marrow-derived mesenchymal stem cells (BMSCs), while the SVVYGLR peptide enhances endothelial progenitor cells (EPCs) vascular differentiation, thus regulating bone metabolism and fostering bone regeneration through the paracrine effects of EPCs. Further mechanistic research demonstrated that PCL-SE promoted the vascularization of EPCs, activating the Notch signaling pathway in BMSCs, leading to the upregulation of osteogenesis-related genes and the downregulation of osteoclast-related genes, thereby restoring bone metabolic balance. Furthermore, PCL-SE facilitated the differentiation of EPCs into "H"-type vessels and the recruitment of BMSCs to synergistically enhance osteogenesis, resulting in the regeneration of normal microvessels and bone tissues in cases of femoral condylar bone defects in osteoporotic SD rats. This study suggests that PCL-SE supports in-situ vascularization, remodels bone metabolic translational balance, and offers a promising therapeutic regimen for osteoporotic bone defects.

Near-Infrared Responsive Properties of Bone Repair Scaffolds Facilitated by Specific Osteoinductive Photothermal Converters for Highly Efficient Bone Repair.

The effective repair of bone defects has long been a major challenge in clinical practice. Currently, research efforts mostly focus on achieving sufficiently good bone repair, with little attention paid to achieving both good and fast repair. However, achieving highly efficient (H-efficient) bone repair, which is both good and fast, can shorten the treatment cycle and facilitate rapid patient recovery. Therefore, the development of a H-efficient bone repair material is of significant importance. This study incorporated the previously developed osteoinductive photothermal agent (PTA) BPICT into printing paste to prepare a near-infrared (NIR)-responsive BPICT scaffold. Subsequently, the effects of photothermal therapy (PTT) on bone repair and drug release were assessed in vitro. To further validate the H-efficient bone repair properties of the BPICT scaffold, the scaffold was implanted into bone defects and its ability to promote bone repair in vivo was evaluated through radiology and histopathological analysis. The results indicated that compared to scaffolds containing only Icaritin (ICT), the BPICT scaffold can achieve PTT to promote bone repair through NIR irradiation, while also enabling the controlled release of ICT from the scaffold to enhance bone repair. Within the same observation period, the BPICT scaffold achieves more efficient bone repair than the ICT scaffold, significantly shortening the bone repair cycle while ensuring the effectiveness of bone repair. Therefore, the NIR-responsive scaffold based on PTT-mediated controlled release of bone growth factors represents a feasible solution for promoting H-efficient bone repair in the area of bone defects.

Epimedium-Curculigo herb pair enhances bone repair with infected bone defects and regulates osteoblasts through LncRNA MALAT1/miR-34a-5p/SMAD2 axis.

Infected bone defects (IBDs) are the common condition in the clinical practice of orthopaedics. Although surgery and anti-infective medicine are the firstly chosen treatments, in many cases, patients experience a prolonged bone union process after anti-infective treatment. Epimedium-Curculigo herb pair (ECP) has been proved to be effective for bone repair. However, the mechanisms of ECP in IBDs are insufficiency. In this study, Effect of ECP in IBDs was verified by micro-CT and histological examination. Qualitative and quantitative analysis of the main components in ECP containing medicated serum (ECP-CS) were performed. The network pharmacological approaches were then applied to predict potential pathways for ECP associated with bone repair. In addition, the mechanism of ECP regulating LncRNA MALAT1/miRNA-34a-5p/SMAD2 signalling axis was evaluated by molecular biology experiments. In vivo experiments indicated that ECP could significantly promote bone repair. The results of the chemical components analysis and the pathway identification revealed that TGF-ß signalling pathway was related to ECP. The results of in vitro experiments indicated that ECP-CS could reverse the damage caused by LPS through inhibiting the expressions of LncRNA MALAT1 and SMAD2, and improving the expressions of miR-34a-5p, ALP, RUNX2 and Collagen type І in osteoblasts significantly. This research showed that ECP could regulate the TGF-ß/SMADs signalling pathway to promote bone repair. Meanwhile, ECP could alleviate LPS-induced bone loss by modulating the signalling axis of LncRNA MALAT1/miRNA-34a-5p/ SMAD2 in IBDs.

Nanobioactive Blood-Derived Shear-Thinning Biomaterial for Tissue Engineering Applications.

The conventional technique for successful bone grafts, involving the use of a patients own tissue (autografts), is challenged by limited availability and donor site morbidity. While allografts and xenografts offer alternatives, they come with the risk of rejection. This underscores the pressing need for tailor-made artificial bone graft materials. In this context, injectable hydrogels are emerging as a promising solution for bone regeneration, especially in complex maxillofacial reconstruction cases. These hydrogels can seamlessly adapt to irregular shapes and conservatively fill defects. Our study introduces a shear-thinning biomaterial by blending silicate nanoplatelets (SNs) enriched with human blood-derived plasma rich in growth factors (PRGF) for personalized applications. Notably, our investigations unveil that injectable hydrogel formulations comprising 7.5% PRGF yield sustained protein and growth factor release, affording precise control over critical growth factors essential for tissue regeneration. Moreover, our hydrogel exhibits exceptional biocompatibility in vitro and in vivo and demonstrates hemostatic properties. The hydrogel also presents a robust angiogenic potential and an inherent capacity to promote bone differentiation, proven through Alizarin Red staining, gene expression, and immunostaining assessments of bone-related biomarkers. Given these impressive attributes, our hydrogel stands out as a leading candidate for maxillofacial bone regeneration application. Beyond this, our findings hold immense potential in revolutionizing the field of regenerative medicine, offering an influential platform for crafting precise and effective therapeutic strategies.

Dynamic Cross-Linking, Self-Healing, Antibacterial Hydrogel for Regenerating Irregular Cranial Bone Defects.

Given the widespread clinical demand, addressing irregular cranial bone defects poses a significant challenge following surgical procedures and traumatic events. In situ-formed injectable hydrogels are attractive for irregular bone defects due to their ease of administration and the ability to incorporate ceramics, ions, and proteins into the hydrogel. In this study, a multifunctional hydrogel composed of oxidized sodium alginate (OSA)-grafted dopamine (DO), carboxymethyl chitosan (CMCS), calcium ions (Ca2+), nanohydroxyapatite (nHA), and magnesium oxide (MgO) (DOCMCHM) was prepared to address irregular cranial bone defects via dynamic Schiff base and chelation reactions. DOCMCHM hydrogel exhibits strong adhesion to wet tissues, self-healing properties, and antibacterial characteristics. Biological evaluations indicate that DOCMCHM hydrogel has good biocompatibility, in vivo degradability, and the ability to promote cell proliferation. Importantly, DOCMCHM hydrogel, containing MgO, promotes the expression of osteogenic protein markers COL-1, OCN, and RUNX2, and stimulates the formation of new blood vessels by upregulating CD31. This study could provide meaningful insights into ion therapy for the repair of cranial bone defects.

Stem Cells in Bone Tissue Engineering: Progress, Promises and Challenges.

Bone defects from accidents, congenital conditions, and age-related diseases significantly impact quality of life. Recent advancements in bone tissue engineering (TE) involve biomaterial scaffolds, patient-derived cells, and bioactive agents, enabling functional bone regeneration. Stem cells, obtained from numerous sources including umbilical cord blood, adipose tissue, bone marrow, and dental pulp, hold immense potential in bone TE. Induced pluripotent stem cells and genetically modified stem cells can also be used. Proper manipulation of physical, chemical, and biological stimulation is crucial for their proliferation, maintenance, and differentiation. Stem cells contribute to osteogenesis, osteoinduction, angiogenesis, and mineralization, essential for bone regeneration. This review provides an overview of the latest developments in stem cell-based TE for repairing and regenerating defective bones.

Sonography in the diagnosis of peri-implant bone defects: An in vitro study on native human mandibles.

AIM: The aim of this study on native human cadavers was to compare clinical, sonographic, and radiological measurements of fenestrations, dehiscences, and 3-wall bone defects on implants. MATERIALS AND METHODS: The examination was carried out on five human mandibles. After the insertion of 27 implants, dehiscences (n = 14), fenestrations (n = 7) and 3-wall bone defects (n = 6) were prepared in a standardized manner. The direct measurement of the bone defects was carried out with a periodontal probe and the radiological examination was carried out using digital volume tomography (DVT). The ultrasound examination (US) was performed using a clinical 24-MHz US imaging probe. Means and standard deviations of the direct, US, and DVT measurements were calculated. Measurements were statistically compared using the Pearson correlation coefficient and Bland-Altman analysis. RESULTS: Bone defects were on average 3.22 ± 1.58 mm per direct measurement, 2.90 ± 1.47 mm using US, and 2.99 ± 1.52 mm per DVT assessment. Pairwise correlations of these measurements were R = .94 (p < .0001) between direct and US, R = .95 (p < .0001) between DVT and US, and R = .96 (p < .0001) between direct and DVT. The mean differences of the measurements (and 95% CI) between direct and US was 0.41 (-0.47 to 1.29), US and DVT 0.33 (-0.30 to 0.97), and direct and DVT 0.28 (-0.50 to 1.07). CONCLUSION: All peri-implant bone defects could be identified and sonographically measured. US measurements showed a strong correlation with direct and DVT measurements. The sonographic measurement accuracy was highest for dehiscences, followed by fenestrations and 3-wall bone defects.

Towards Stem Cell Therapy for Critical-Sized Segmental Bone Defects: Current Trends and Challenges on the Path to Clinical Translation.

The management and reconstruction of critical-sized segmental bone defects remain a major clinical challenge for orthopaedic clinicians and surgeons. In particular, regenerative medicine approaches that involve incorporating stem cells within tissue engineering scaffolds have great promise for fracture management. This narrative review focuses on the primary components of bone tissue engineering-stem cells, scaffolds, the microenvironment, and vascularisation-addressing current advances and translational and regulatory challenges in the current landscape of stem cell therapy for critical-sized bone defects. To comprehensively explore this research area and offer insights for future treatment options in orthopaedic surgery, we have examined the latest developments and advancements in bone tissue engineering, focusing on those of clinical relevance in recent years. Finally, we present a forward-looking perspective on using stem cells in bone tissue engineering for critical-sized segmental bone defects.

A new classification to characterize and predict treatment of acetabular bone defects.

BACKGROUND: The increasing amount of revision surgeries in total hip arthroplasty (THA) represents a burden for orthopedic surgeons given the complexity and unpredictability of this kind of surgery. The aim of the current study was to develop a new radiographic classification of acetabular bone defects stratify the severity of the lesion and to suggest the surgical strategy to address it. METHODS: Radiographs of 151 consecutive patients who underwent acetabular revision surgery in our institution were collected to develop a new classification that groups the acetabular bone defects in three zones (A, B and C). The performance to predict treatment and inter- and intra-rater agreement were evaluated. RESULTS: The ability of the newly proposed classification to predict treatment was 87.3% (k weighted: 0.65). The inter-rater reliability was 90.1% (k: 0.81), and the intra-rater reliability between the two sets of evaluations performed by the observer at 1-month distance was 97.5% (k: 0.94). CONCLUSIONS: The newly proposed classification was able to characterize the extent of acetabular bone defects and predict pre-operatively the appropriate surgical treatment strategy in 87.3% of cases. It showed a strong agreement among raters and an almost perfect agreement among different measurements at 1 month distance. This new tool could be used in the preoperative assessment to drive the use of secondary level image examinations and the type of surgical management.

Dentin-derived alveolar bone graft for alveolar augmentation: A systematic review.

Introduction: Application of alveolar bone graft (ABG) in alveolar augmentation is done to prevent excessive bone resorption due to tooth extraction, missing teeth, or other diseases/conditions affecting the alveolar bone. The use of autogenous dentin-derived ABG has been considered as the composition of dentin appears to be nearly analogous to that of bone. Objective: This systematic review aims to assess the efficacy of dentin-derived ABG for alveolar augmentation of post-extraction sockets or other alveolar bone defects by evaluating volume gain and histomorphometric data. Material and methods: A search of systematic literature was conducted in Pubmed, Scopus, Web of Science, and Embase from database inception to October 2023. The review included both randomized controlled trials (RCT), pilot studies, clinical trials, and retrospective studies reporting on dentin-derived ABG use for alveolar augmentation. Results: Overall, 298 articles were obtained from the initial search. From these articles, 21 articles met the inclusion criteria and were included for descriptive analysis. All of the studies indicated low risk of bias. Studies of dentin-derived ABG, which used bone-derived grafts as the control group, have shown significantly higher percentages of new bone formation, gain in vertical and horizontal dimensions, and less reduction in dimensions. Conclusions: Dentin-derived ABG was effective in volume maintenance, indicating promising results via histomorphometric and radiographic analysis.

Engineered phalangeal grafts for children with symbrachydactyly: A proof of concept.

Tissue engineering approaches hold great promise in the field of regenerative medicine, especially in the context of pediatric applications, where ideal grafts need to restore the function of the targeted tissue and consider growth. In the present study, we aimed to develop a protocol to engineer autologous phalangeal grafts of relevant size for children suffering from symbrachydactyly. This condition results in hands with short fingers and missing bones. A previously-described, developmentally-inspired strategy based on endochondral ossification (ECO)-the main pathway leading to bone and bone marrow development-and adipose derived-stromal cells (ASCs) as the source of chondroprogenitor was used. First, we demonstrated that pediatric ASCs associated with collagen sponges can generate hypertrophic cartilage tissues (HCTs) in vitro that remodel into bone tissue in vivo via ECO. Second, we developed and optimized an in vitro protocol to generate HCTs in the shape of small phalangeal bones (108-390 mm3) using freshly isolated adult cells from the stromal vascular fraction (SVF) of adipose tissue, associated with two commercially available large collagen scaffolds (Zimmer Plug® and Optimaix 3D®). We showed that after 12 weeks of in vivo implantation in an immunocompromised mouse model such upscaled grafts remodeled into bone organs (including bone marrow tissues) retaining the defined shape and size. Finally, we replicated similar outcome (albeit with a slight reduction in cartilage and bone formation) by using minimally expanded pediatric ASCs (3 × 106 cells per grafts) in the same in vitro and in vivo settings, thereby validating the compatibility of our pediatric phalanx engineering strategy with a clinically relevant scenario. Taken together, these results represent a proof of concept of an autologous approach to generate osteogenic phalangeal grafts of pertinent clinical size, using ASCs in children born with symbrachydactyly, despite a limited amount of tissue available from pediatric patients.

Exploring calcium-free alternatives in endochondral bone repair tested on In vivo trials - A review.

Bone repair via endochondral ossification is a complex process for the critical size reparation of bone defects. Tissue engineering strategies are being developed as alternative treatments to autografts or allografts. Most approaches to bone regeneration involve the use of calcium composites. However, exploring calcium-free alternatives in endochondral bone repair has emerged as a promising way to contribute to bone healing. By analyzing researches from the last ten years, this review identifies the potential benefits of such alternatives compared to traditional calcium-based approaches. Understanding the impact of calcium-free alternatives on endochondral bone repair can have profound implications for orthopedic and regenerative medicine. This review evaluates the efficacy of calcium-free alternatives in endochondral bone repair through in vivo trials. The findings may guide future research to develop innovative strategies to improve endochondral bone repair without relying on calcium. Exploring alternative approaches may lead to the discovery of novel therapies that improve bone healing outcomes.

Surface bioactivation of Polyetheretherketone (PEEK) by magnesium chondroitin sulfate (MgCS) as orthopedic implants for reconstruction of skeletal defects.

Polyether-ether-ketone (PEEK) is clinically used as a bio-implant for the healing of skeletal defects. However, the osseointegration of clinical-sized bone grafts remains limited. In this study, surface-porous PEEK was created by using a sulfonation method and a metal-polysaccharide complex MgCS was introduced on the surface of sulfonated PEEK to form MgCS@SPEEK. The as-prepared MgCS@SPEEK was found to have a porous surface with good hydrophilicity and bioactivity. This was followed by an investigation into whether MgCS loaded onto sulfonated PEEK surfaces could promote osseointegration and angiogenesis. The in vitro results showed that MgCS@SPEEK had a positive effect on reducing the expression levels of inflammatory genes and promoting osteogenesis and angiogenesis-related genes expression levels. Furthermore, porous MgCS@SPEEK was implanted in critical-sized rat tibial defects for in vivo evaluation of osseointegration. The micro-computed tomography evaluation results revealed substantial bone formation at 4 and 8 weeks. Collectively, these findings indicate that MgCS@SPEEK could provide improved osseointegration and an attractive strategy for orthopaedic applications.

A sponge-like nanofiber melatonin-loaded scaffold accelerates vascularized bone regeneration via improving mitochondrial energy metabolism.

Electrospun nanofibers have been widely employed in bone tissue engineering for their ability to mimic the micro to nanometer scale network of the native bone extracellular matrix. However, the dense fibrous structure and limited mechanical support of these nanofibers pose challenges for the treatment of critical size bone defects. In this study, we propose a facile approach for creating a three-dimensional scaffold using interconnected electrospun nanofibers containing melatonin (Scaffold@MT). The hypothesis posited that the sponge-like Scaffold@MT could potentially enhance bone regeneration and angiogenesis by modulating mitochondrial energy metabolism. Melatonin-loaded gelatin and poly-lactic-acid nanofibers were fabricated using electrospinning, then fragmented into shorter fibers. The sponge-like Scaffold@MT was created through a process involving homogenization, low-temperature lyophilization, and chemical cross-linking, while maintaining the microstructure of the continuous nanofibers. The incorporation of short nanofibers led to a low release of melatonin and increased Young's modulus of the scaffold. Scaffold@MT demonstrated positive biocompatibility by promoting a 14.2 % increase in cell proliferation. In comparison to the control group, Scaffold@MT significantly enhanced matrix mineralization by 3.2-fold and upregulated the gene expression of osteoblast-specific markers, thereby facilitating osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs). Significantly, Scaffold@MT led to a marked enhancement in the mitochondrial energy function of BMMSCs, evidenced by elevated adenosine triphosphate (ATP) production, mitochondrial membrane potential, and protein expression of respiratory chain factors. Furthermore, Scaffold@MT promoted the migration of human umbilical vein endothelial cells (HUVECs) and increased tube formation by 1.3 times compared to the control group, accompanied by an increase in vascular endothelial growth factor (VEGFA) expression. The results of in vivo experiments indicate that the implantation of Scaffold@MT significantly improved vascularized bone regeneration in a distal femur defect in rats. Micro-computed tomography analysis conducted 8 weeks post-surgery revealed that Scaffold@MT led to optimal development of new bone microarchitecture. Histological and immunohistochemical analyses demonstrated that Scaffold@MT facilitated bone matrix deposition and new blood vessel formation at the defect site. Overall, the utilization of melatonin-loaded nanofiber sponges exhibits significant promise as a scaffold that promotes bone growth and angiogenesis, making it a viable option for the repair of critical-sized bone defects.

A review of 10 patients treated with the masquelet technique and microsurgical technique combined for Gustilo type III open tibial fractures.

BACKGROUND: Open tibial fractures often include severe bone loss and soft tissue defects and requires complex reconstructive operations. However, the optimal treatment is unclear. METHODS: This retrospective study enrolled patients with Gustilo type III open tibial fractures from January 2018 to January 2021 to assess the clinical utility of Masquelet technique together with microsurgical technique as a combined strategy for the treatment of open tibial fractures. The demographics and clinical outcomes including bone union time, infection, nonunion and other complications were recorded for analysis. The bone recovery quality was evaluated by the AOFAS Ankle-Hindfoot Scale score and the Paley criteria. RESULTS: We enrolled 10 patients, the mean age of the patients and length of bone defects were 31.7 years (range, 23-45 years) and 7.5 cm (range, 4.5-10 cm) respectively. Bone union was achieved for all patients, with an average healing time of 12.2 months (range, 11-16 months). Seven patients exhibited a bone healing time of less than 12 months, whereas 3 patients exhibited a bone healing time exceeding 12 months. No significant correlation was found between the length of bone loss and healing time. In addition, no deep infection or nonunion was observed, although 2 patients experienced wound fat liquefaction with exudates and 1 patient presented with a bloated skin flap. The average AOFAS Ankle-Hindfoot Scale score was 80.5 (range, 74-85), and all patients were evaluated as good or exellent based on the Paley criteria. CONCLUSIONS: Our study indicated that the use of the Masquelet technique and the microsurgical technique as a combined strategy is safe and effective for the treatment of Gustilo type III open tibial fractures.

The influence of connective tissue grafting on the reconstruction of a missing facial bone wall using immediate implant placement and simultaneous bone reconstruction: a retrospective long-term cohort study.

PURPOSE: This retrospective cohort study evaluates the influence of connective tissue grafts (CTG) on bone regeneration at implant sites with total loss of the buccal bone wall treated with flapless immediate implant placement (IIP) and reconstruction with autogenous bone chips (AB) within a follow-up of up to 13 years. METHODS: Sixty implants were inserted in 55 patients in sites with total loss of the buccal bone wall between 2008 and 2021. The implants were inserted and the buccal gaps were grafted by AB. A subgroup of 34 sites was grafted additionally with CTG using tunnel technique. Primary outcome was the vertical bone regeneration in height and thickness. Secondary outcome parameters were interproximal marginal bone level, recession, soft tissue esthetics (PES), width of keratinized mucosa (KMW) and probing depths (PPD). RESULTS: Mean follow-up period was 60.8 months. In 55 sites a complete vertical bone regeneration was documented. The mean buccal bone level increased by 10.6 mm significantly. The thickness of the buccal bone wall ranged between 1.7 and 1.9 mm, and was significantly thicker in sites without CTG. Interproximal marginal bone level was at implant shoulder level. The mean recession improved significantly by 1.2 mm. In sites with CTG, recessions and PES improved significantly more. CONCLUSIONS: Additional CTG in extraction sites with total buccal bone loss followed by IIP with simultaneous AB grafting led to improved PES and recession, but also to a thinner buccal bone wall compared to sites grafted just with AB.

Nanofiber-induced hierarchically-porous magnesium phosphate bone cements accelerate bone regeneration by inhibiting Notch signaling.

Magnesium phosphate bone cements (MPC) have been recognized as a viable alternative for bone defect repair due to their high mechanical strength and biodegradability. However, their poor porosity and permeability limit osteogenic cell ingrowth and vascularization, which is critical for bone regeneration. In the current study, we constructed a novel hierarchically-porous magnesium phosphate bone cement by incorporating extracellular matrix (ECM)-mimicking electrospun silk fibroin (SF) nanofibers. The SF-embedded MPC (SM) exhibited a heterogeneous and hierarchical structure, which effectively facilitated the rapid infiltration of oxygen and nutrients as well as cell ingrowth. Besides, the SF fibers improved the mechanical properties of MPC and neutralized the highly alkaline environment caused by excess magnesium oxide. Bone marrow stem cells (BMSCs) adhered excellently on SM, as illustrated by formation of more pseudopodia. CCK8 assay showed that SM promoted early proliferation of BMSCs. Our study also verified that SM increased the expression of OPN, RUNX2 and BMP2, suggesting enhanced osteogenic differentiation of BMSCs. We screened for osteogenesis-related pathways, including FAK signaing, Wnt signaling and Notch signaling, and found that SM aided in the process of bone regeneration by suppressing the Notch signaling pathway, proved by the downregulation of NICD1, Hes1 and Hey2. In addition, using a bone defect model of rat calvaria, the study revealed that SM exhibited enhanced osteogenesis, bone ingrowth and vascularization compared with MPC alone. No adverse effect was found after implantation of SM in vivo. Overall, our novel SM exhibited promising prospects for the treatment of critical-sized bone defects.

Proximal femoral defect classifications in revision total hip arthroplasty from X-rays imaging to advanced 3D imaging: a narrative review.

Background and Objective: Femoral bone defect in hip arthroplasty revision surgery represents a complex problem, and the treatment is a challenge for orthopedic surgeons called to assess the residual bone stock in an altered anatomy and obtain stability for the new implant. Classification systems available are mostly based on X-rays two-dimensional images and lack of accuracy and reproducibility and comprehensive therapeutic algorithms. However, there is no record of any classification based on computed tomography (CT)-scan images or three-dimensional (3D) modeling modern techniques. We aimed to review the current literature around femoral defect classifications (FDCs) analyzing their different rationale basis, reliability and accuracy, and their benefit in clinical practice. Moreover, we highlighted the role of CT scan-based 3D modeling techniques in the setting of femoral bone defects and revision hip arthroplasty. Methods: A narrative review was conducted. The articles were selected from the PubMed and Scopus medical database updated to March 2023. All Level-I to IV studies in the English language were considered for inclusion. The research was performed using relevant search term items: "femoral defects", "classification", "radiographic", "revision hip arthroplasty", "CT scan" and "3D" and we included only articles that evaluated the accuracy or reliability (or both) of the different femoral bone defects classification system. Key Content and Findings: Our search yielded 408 results, of which 17 were deemed highly relevant. We found seven X-ray-based classification systems which have been attempted to quantify the degree of bone loss with low to good reproducibility. The most used classification system for femoral bone defects were the AAOS and Paprosky classification, which also offers a clinical therapeutic algorithm. In 2021, the FDC interestingly showed a new simple classification system with sub-optimal reproducibility and a practical therapeutic algorithm. Despite the numerous classification system of femoral defects, none of them comprehends the use of CT scan and 3D imaging technologies. Conclusions: Traditional X-rays-based classification system are still widely used event if their intra-observer and inter-observer reliability is sub-optimal. 3D modeling techniques represent an important diagnostic tool that could improve the understanding of bone defects and residual bone supportive structures, allowing to elaborate new, more precise, classification systems.