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Treatment of bone defects resulting after tumor surgeries, accidents, or non-unions is an actual problem linked to morbidity and the necessity of a second surgery and often requires a critical healthcare cost. Although the surgical technique has changed in a modern way, the treatment outcome is still influenced by patient age, localization of the bone defect, associated comorbidities, the surgeon approach, and systemic disorders. Three-dimensional magnesium-based scaffolds are considered an important step because they can have precise bone defect geometry, high porosity grade, anatomical pore shape, and mechanical properties close to the human bone. In addition, magnesium has been proven in in vitro and in vivo studies to influence bone regeneration and new blood vessel formation positively. In this review paper, we describe the magnesium alloy's effect on bone regenerative processes, starting with a short description of magnesium's role in the bone healing process, host immune response modulation, and finishing with the primary biological mechanism of magnesium ions in angiogenesis and osteogenesis by presenting a detailed analysis based on a literature review. A strategy that must be followed when a patient-adapted scaffold dedicated to bone tissue engineering is proposed and the main fabrication technologies are combined, in some cases with artificial intelligence for Mg alloy scaffolds, are presented with examples. We emphasized the microstructure, mechanical properties, corrosion behavior, and biocompatibility of each study and made a basis for the researchers who want to start to apply the regenerative potential of magnesium-based scaffolds in clinical practice. Challenges, future directions, and special potential clinical applications such as osteosarcoma and persistent infection treatment are present at the end of our review paper. [ABSTRACT FROM AUTHOR]

Black Phosphorus (BP) is a new semiconductor material with excellent biocompatibility, degradability, and optical and electrophysical properties. A growing number of studies show that BP has high potential applications in the biomedical field. This article aims to systematically review the research progress of BP composite medical materials in the field of tissue engineering, mining BP in bone regeneration, skin repair, nerve repair, inflammation, treatment methods, and the application mechanism. Furthermore, the paper discusses the shortcomings and future recommendations related to the development of BP. These shortcomings include stability, photothermal conversion capacity, preparation process, and other related issues. However, despite these challenges, the utilization of BP-based medical materials holds immense promise in revolutionizing the field of tissue repair. [ABSTRACT FROM AUTHOR]

PURPOSE OF THE STUDY The preclinical study aimed to compare the healing of segmental bone defects treated with biodegradable hyaluronic acid and tricalcium phosphate-based hydrogel with the established autologous spongioplasty. Another aim was to evaluate the hydrogel as a scaffold for osteoinductive growth factor of bone morphogenetic protein-2 (BMP-2) and stem cells. MATERIAL AND METHODS The study was conducted in an in vivo animal model. A standardized rabbit model of a 15 mm long segmental bone defect of left radius was used. A total of 40 animals were divided into 5 groups of 8 individuals. In the KO- (negative control) group, the created defect was left to heal spontaneously. In the KO+ (positive control) group, the defect was filled with morselized bone autograft prepared from the resected segment. In the study group A, the defect was filled with hydrogel based on hyaluronic acid derivative and tricalcium phosphate. In the study group B, the defect was filled with hydrogel based on hyaluronic acid derivative, tricalcium phosphate and bone marrow aspirate. In the study group C, the defect was filled with hydrogel based on hyaluronic acid derivative, tricalcium phosphate, bone marrow aspirate and BMP-2. Healing was assessed using radiographs at 1, 6, and 12 weeks postoperatively and histology specimens were collected at 16 weeks postoperatively. RESULTS Altogether 35 rabbits survived (KO- 7, KO+ 7, A 7, B 6, C 8) until the end of the study. As concerns the radiographic assessment, the best results were achieved by the groups KO+ and C, where new bone formation across the entire width of the bone defect was clearly seen at 6 and 12 weeks and the osteotomy line was completely healed too. At 12 weeks, complete bone remodelling was observed in all animals in the group KO+, whereas in the group C, bone remodelling was fully completed in 5 animals and partially completed in 3 animals. In terms of histological assessment, however, the best results were achieved by the group C, where the bone defect was completely remodelled into lamellar bone in 7 specimens, while in 1 specimen it healed with bony callus formation. In the group KO+, the defect was healed in 4 specimens by cartilaginous callus with loci of remodelling into bony callus, in 2 specimens the bony callus was predominant with cartilaginous callus areas, and only one defect was completely remodelled into lamellar bone. DISCUSSION Compared to autografts that manifest osteogenic, osteoinductive and osteoconductive properties, the biodegradable hyaluronic acid and tricalcium phosphate-based hydrogel has osteoconductive properties only. Thus, it was also tested in our study as a scaffold for bone marrow cells and BMP-2 osteoinductive growth factor. Thanks to its semi-liquid properties, the biodegradable hyaluronic acid and tricalcium phosphate-based hydrogel is a promising material for use in 3D printing. CONCLUSIONS The preclinical study in an in vivo animal model confirmed the beneficial effect of the biodegradable hyaluronic acid and tricalcium phosphate-based hydrogel on the healing of critical-size segmental bone defects. Better healing of these defects was also confirmed for filling composed of hydrogel and BMP-2 osteoinductive growth factor. The benefit of bone marrow aspirate mixed with hydrogel was not confirmed. [ABSTRACT FROM AUTHOR]

Hydroxyapatite (HA)-based materials are widely used in the bone defect restoration field due to their stable physical properties, good biocompatibility, and bone induction potential. To further improve their performance with extra functions such as antibacterial activity, various kinds of metal ion-doped HA-based materials have been proposed and synthesized. This paper offered a comprehensive review of metal ion-doped HA-based materials for bone defect restoration based on the introduction of the physicochemical characteristics of HA followed by the synthesis methods, properties, and applications of different kinds of metal ion (Ag+, Zn2+, Mg2+, Sr2+, Sm3+, and Ce3+)-doped HA-based materials. In addition, the underlying challenges for bone defect restoration using these materials and potential solutions were discussed. [ABSTRACT FROM AUTHOR]

Bones play an important role in maintaining exercise and protecting organs. Bone defect, as a common orthopedic disease in clinics, can cause tremendous damage with long treatment cycles. Therefore, the treatment of bone defect remains as one of the main challenges in clinical practice. Today, with increased incidence of bone disease in the aging population, demand for bone repair material is high. At present, the method of clinical treatment for bone defects including non-invasive therapy and invasive therapy. Surgical treatment is the most effective way to treat bone defects, such as using bone grafts, Masquelet technique, Ilizarov technique etc. In recent years, the rapid development of tissue engineering technology provides a new treatment strategy for bone repair. This review paper introduces the current situation and challenges of clinical treatment of bone defect repair in detail. The advantages and disadvantages of bone tissue engineering scaffolds are comprehensively discussed from the aspect of material, preparation technology, and function of bone tissue engineering scaffolds. This paper also summarizes the 3D printing technology based on computer technology, aiming at designing personalized artificial scaffolds that can accurately fit bone defects. [ABSTRACT FROM AUTHOR]

Background: The induced membrane technique (IMT) is a two-step procedure used for reconstructing segmental bone defects in the limbs. The osteogenic mechanism after bone grafting using IMT remains unclear, and efforts to modify the original techniques are limited to the investigative phase. Therefore, reviewing existing knowledge and identifying hotspots and new trends in IMT is critical. Methods: We retrieved reviews and articles associated with IMT published between 2004 and 2023 from the Web of Science Core Collection (WoSCC). The keywords included induced membrane technique, guided bone regeneration, bone defect reconstruction, bone graft, stem cells, Masquelet technique, management of bone defects, and scaffold. HistCite, VOSviewer, CiteSpace, and R-bibliometrics were used for scientometric analysis. Results: A total of 1019 publications from 374 academic journals with 33,995 co-cited references by 2,331 institutions from 65 countries or regions were included. China (n = 235) and the United States (n = 215) were the most productive countries, with Shanghai Jiao Tong University producing the most number of publications (n = 18). Journal Injury [co-citations = 1774; impact factor (IF) 2022 = 2.5] published the most manuscripts, while Masquelet AC and Giannoudis PV published literature with a significant influence on IMT, showing more co-citations (n = 727; n = 355). Two preface hotspots of IMT focused on investigating the microscopic mechanism (such as the membrane supporting graft-to-bone union and the role of inflammatory cells) and developing new techniques to improve IMT (such as bone tissue engineering and new drugs). Conclusion: This study comprehensively reviewed the literature about IMT published in the last 20 years using qualitative and quantitative methods, providing valuable information for researchers investigating IMT. [ABSTRACT FROM AUTHOR]

Background: This paper aimed to propose a modified technique of bone transport. An annular frame combined with a retrograde tibiotalocalcaneal arthrodesis nail was used in this novel technique for treating large distal tibial periarticular osteomyelitis and associated defects. Methods: Our team conducted a retrospective research. Forty-three patients with large distal tibial periarticular bone loss were involved in this study. Sixteen patients were treated using the modified hybrid transport technique (MHT group) while 27 were subjected to traditional bone transport (BT group). The mean bone loss was 7.8 ± 2.4 cm in the MHT group and 7.6 ± 2.6 cm in the BT group. The external fixation index, time in transport frame, self-rating anxiety scale, bone healing results and postoperative complications were recorded. Results: The mean time in frame for the MHT group was 3.6 ± 1.5 months, while that of the BT group was 10.3 ± 2.7 months (p < 0.05). The mean external fixation index of MHT group was 0.46 ± 0.08 months/cm versus 1.38 ± 0.24 months/cm of the BT group (p < 0.05). There was no statistical difference for the bone healing results between the MHT and BT groups (p = 0.856). The self-rating anxiety scale and total complication incidence of the MHT group were significantly lower than that of BT patients (p < 0.05). Conclusion: Compared to the traditional BT technique, our modified hybrid transport technique showed better clinical outcomes for treating large distal tibial periarticular bone loss, including less time in transport frame, lower external fixation index and complication incidence. Therefore, this modified technique should be further promoted and developed. [ABSTRACT FROM AUTHOR]

Background: Early detection of peri-implant bone defects can improve long-term durability of dental implants. By the advances in cone-beam computed tomography (CBCT) scanners and introduction of new algorithms, it is important to find the most efficient protocol for detection of bone defects. This study aimed to assess the efficacy of metal artifact reduction (MAR) and advanced noise reduction (ANR) algorithms for detection of peri-implant bone defects. Materials and methods: In this in vitro study, 40 titanium implants were placed in 7 sheep mandibles. Crestal, apical, and Full defects (n = 10 from each type) were created around the implants, and 10 implants were also placed as controls. CBCT scans were obtained in four modes: with MAR, with ANR, with both MAR and ANR, and without any filter. Totally, 28 scans were obtained and evaluated by a radiologist and a maxillofacial surgeon. The observers recorded their observations in a checklist, and data were analyzed by SPSS version 21 using the kappa coefficient of agreement, sensitivity and specificity values, area under the receiver operating characteristic (ROC) curve (AUC), intraclass correlation coefficient, t-test and paired t-test (P < 0.05). Results: The inter-observer agreement was high for detection of all defects in all modes except with ANR. No significant difference was found in AUC and diagnostic accuracy of different scan modes (P > 0.05). The most common diagnostic error was related to misdiagnosis of control group with full defect with ANR filter, such that the existing bone was not detected. Defect depth was averagely over-estimated while defect length was under-estimated. Correct diagnosis of defects had the highest frequency when both filters were on. Conclusion: The diagnostic accuracy and sensitivity for detection of different defect types were not significantly different in different scan modes but activation of ANR filter significantly decreased the specificity and positive predictive value compared with no use of filter. [ABSTRACT FROM AUTHOR]

Osteoporotic fractures are characterized by abnormal inflammation, deterioration of the bone microenvironment, weakened mechanical properties, and difficulties in osteogenic differentiation. The chronic inflammatory state characterized by aging macrophages leads to delayed or non‐healing of the fracture or even the formation of bone defects. The current bottleneck in clinical treatment is to achieve strong fixation of the comminuted bone fragments and effective regulation of the complex microenvironment of aging macrophages. Inspired by cement and gravel in concrete infrastructure, a biomimetic bone glue with poly(lactic‐co‐glycolic acid) microspheres is developed and levodopa/oxidized chitosan hydrogel stabilized on an organic‐inorganic framework of nanohydroxyapatite, named DOPM. DOPM is characterized via morphological and mechanical characterization techniques, in vitro experiments with bone marrow mesenchymal stromal cells, and in vivo experiments with an aged SD rat model exhibiting osteoporotic bone defects. DOPM exhibited excellent adhesion properties, good biocompatibility, and significant osteogenic differentiation. Transcriptomic analysis revealed that DOPM improved the inflammatory microenvironment by inhibiting the NF‐κB signaling pathway and promoting aging macrophage polarization toward M2 macrophages, thus significantly accelerating bone defect repair and regeneration. This biomimetic bone glue, which enhances osteointegration and reestablishes the homeostasis of aging macrophages, has potential applications in the treatment of osteoporotic bone defects. [ABSTRACT FROM AUTHOR]

Background: Bone defects and nonunion following initial treatment remain significant clinical challenges. The Ilizarov method constitutes a fundamental approach for addressing bone defects, and its integration with adjunctive techniques, such as the accordion maneuver, antibiotic spacers, or internal fixation, has become increasingly widespread. Despite this, limited research exists on the clinical outcomes specifically related to the use of the Ilizarov method combined with the accordion technique for treating long bone defects in the lower limbs. Objective: This study seeks to systematically review the application of the Ilizarov method in combination with the accordion technique for addressing long bone deficiencies in the lower limbs. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review was performed in alignment with the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), involving searches of Medline, Embase, Web of Science, and the Cochrane Library, with the search process concluding on August 20, 2024. The study population consisted of patients with bone defects who underwent treatment using the Ilizarov method in conjunction with the accordion technique. The methodological quality of the included studies was evaluated using the MINORS (Methodological Index for Non-Randomized Studies) scoring system. This study recorded and analyzed the participant count for each study that met the inclusion criteria, along with the number of patients who achieved bone healing, the bone and functional outcomes, and complications such as pin infections, pain, and refracture. Results: Drawing from eight studies involving 80 patients with bone defects treated through the Ilizarov method combined with the accordion technique, this systematic review evaluated the method's impact on bone regeneration. Of these patients, 24% presented with femoral defects, while 76% had tibial defects. The mean patient age was 32.8 years, with an average follow-up of 25.2 months. The accordion technique involved daily distraction and compression adjustments ranging from 0.25 to 1 mm, typically in more than two cycles, effectively promoting bone healing. The bone healing rate was high, with the majority of patients rated as having excellent or good functional recovery, according to standards such as ASAMI and Paley. Common complications included superficial pin tract infections (33.75%) and deep pin tract infections (6.25%), both of which were generally manageable with routine treatment. The accordion technique showed promising results in shortening healing time and enhancing the quality of bone healing. Conclusion: This systematic review demonstrates that despite variations in parameter settings across studies, the Ilizarov method combined with the accordion technique consistently shows strong efficacy and safety in promoting bone regeneration and functional recovery. While some complications may arise, they are generally well-managed with standard care. This approach represents a reliable option for complex bone reconstruction, with future research needed to optimize parameters and further enhance clinical outcomes. [ABSTRACT FROM AUTHOR]

Aim: Studying in rabbit model, the bone behavior during the process of osseointegration of dental implants mimicking vitamin deficiency D3. Materials and Methods: Six rabbits received implants in the area of the removed lower first incisor after creating a condition of vitamin D3 deficiency. Afterwards, the examinations were carried out on days 3, 5, 7, 30, and 90 when all animals were removed from the experiment. At that time, a bone block was collected within the installed dental implant, with the intact area and the area of the adjacent tooth. The samples were examined by histomorphometry analysis. Results: In rabbits with vitamin D3 deficiency, dental implants could be osseointegrated by the regeneration of the bone tissues after surgeries. However, a decrease in the number of cells involved in the construction of bone tissue—osteocytes—was recorded in the regenerated bone (40% ± 7%) as compared with the native bone immediately after implantation, before the bone remodeling processes. Conclusions: The study's results on the rabbit model in vivo confirmed the relationship between vitamin D3 and the process of osseointegration. This in vivo experiment can be the basis for future clinical study. [ABSTRACT FROM AUTHOR]

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Background. The problem of management of bone tissue defects remains one of the tasks that a surgeon faces during primary total knee arthroplasty (TKA). Since the number of TKA is increasing every year, modern scientific research aimed at solving the problem of bone defect replacement remains important. The aim of the study was to evaluate the effectiveness of various methods of bone defects management in primary TKA based on the analysis of literature. Materials and Methods. We conducted a search of articles in PubMed, eLIBRARY, Scopus from 2005 to 2020. Results. On the whole our search led to 1217 papers. Finally 19 articles that met inclusion criteria were included in this review. Each of the methods of bone defect replacement has its advantages and disadvantages. The results of the studies show that the he defect size is not a key factor for choosing the method, since with relatively identical defect parameters, different plastic options were used with a satisfactory clinical outcome. The endoprosthesis component should be fixed in at least two zones in every chosen method. In young patients with good bone quality preference in chosen methods should be given to bone grafts, which allow to preserve the bone stock. Based on the papers analysis, we have proposed the algorithm for method choosing for each clinical case. Conclusion. Each surgeon chooses a method for replacing bone defects based on their own preferences and such criteria as the equipment of the operating room, the surgical team experience, the quality of the patients bone and the defect size.

Purpose: The present study aimed to evaluate and compare the effect of nanofibrillated cellulose (NFC)‐based composite with dicalcium phosphate dihydrate and an autologous blood clot (ABC) on the formation of new bone tissue in vivo by histological and histomorphometric assessment. Materials and Methods: A total of 72 rats with created femoral defects (2 mm) were used. The rats were divided into three groups: (1) with filling of the defect with an ABC, (2) NFC‐1—with filling of both the cortical plate and intramedullary space in the defect area, and (3) NFC‐2—with filling of only the intramedullary space in the defect area. Histological and histomorphometric analysis was performed to assess the healing of the bone defect after 14, 30 and 60 days. Results: Complete closure of the cortical plate defect was detected in the NFC‐2 group on Day 30 (p < 0.0001). Moreover, in both NFC groups on the 30th and 60th days, ongoing osteogenesis was observed, characterized by a large volume of newly formed circular pattern bone tissue in the intramedullary space. Сonclusion: This study demonstrated that the NFC‐based composite, which is located below the level of the cortical plate, tamponing only the intramedullary space (NFC‐2), improves bone tissue repair at the site of a bone defect of the cortical plate and has the potential of prolonged osteoinductivity. Level of Evidence: Not applicable. [ABSTRACT FROM AUTHOR]

Background Ceramic materials are currently in wide demand in various fields of medicine. Zirconium ceramics demonstrate exceptional mechanical properties and biocompatibility and do not cause cytotoxic effects or allergic reactions in surrounding tissues. The objective was to present an analysis of current literature data on the use of zirconium ceramics as a bone replacement material in traumatology and orthopaedics. Materials and methods The search for publications was conducted using the databases of Scopus, PubMed and the electronic scientific library eLIBRARY in the Russian and English languages using the keywords: bioceramics, bone, bone defect, zirconate, zirconium ceramics, bone tissue engineering, implant, scaffold, augment, biointegration, bioactivity. Depth of search for scientific papers was from 2000 to 2023. Results and discussion Zirconium dioxide is the main ceramic bioinert material. The study presents the characteristics of ZrO2 as a bone replacement material and its comparison with titanium implants. Data are presented on various strategies for improving zirconium bioceramics: improving the surface of the material by physical and chemical methods, obtaining volumetric porosity, including using additive technologies, creating composite materials, and developing bioactive coatings. New methods of creating zirconium ceramics compatible with living tissues containing bioactive ions that promote both osseointegration and bone tissue regeneration have been actively studied. Conclusions Zirconium dioxide ceramics appear to be a promising alternative to titanium implants in terms of mechanical strength, biological functionality, chemical stability, osseointegration, and antibacterial properties. Future experimental and clinical studies will further improve zirconium ceramics.

Simple Summary: The aim of this study is to review the available information on the use of avian eggshell as bone regeneration material. Five databases were searched up to October 2020. Animal studies with a bone defect model using eggshell as a grafting material were included. Risk of bias and the quality of the papers were assessed. Overall, a total of 581 studies were included in the study, 187 after duplicate removal. Using the inclusion and exclusion criteria 167 records were further excluded. The full text of the remaining 20 articles was assessed for eligibility and included in the review. There were different methods of obtaining eggshell for grafting purposes. Eggshell is a biocompatible grafting material, with bone formation capabilities. It forms new bone similar to other products currently in use in clinical practice. It can be combined with other materials to enhance its proprieties. Eggshell is a promising biomaterial to be used in bone grafting procedures, though further research is needed. The aim of this study is to systemically review the available evidence on the in vivo behavior of eggshell as a guided bone regeneration substitute material. Five databases (PubMed, Cochrane, Web of Science, Scopus, EMBASE) were searched up to October 2020. In vivo animal studies with a bone defect model using eggshell as a grafting material were included. Risk of bias was assessed using SYRCLE tool and the quality assessment using the ARRIVE guidelines. Overall, a total of 581 studies were included in the study, 187 after duplicate removal. Using the inclusion and exclusion criteria 167 records were further excluded. The full text of the remaining 20 articles was assessed for eligibility and included in the qualitative and quantitative assessment synthesis. There were different methods of obtaining eggshell grafting materials. Eggshell is a biocompatible grafting material, with osteoconduction proprieties. It forms new bone similar to Bio-Oss and demineralized freeze-dried bone matrix. It can be combined with other materials to enhance its proprieties. Due to the high variability of the procedures, animals, production and assessment methods, no meta-analysis could be performed. Eggshell might be considered a promising biomaterial to be used in bone grafting procedures, though further research is needed. [ABSTRACT FROM AUTHOR]