Treatment Of Large Bone Defects Research Articles

Enhancement of a one-step membrane technique for the treatment of large bone defects by pre-seeding the membrane with CD8 lymphocyte depleted bone marrow mononuclear cells in a rat femoral defect model

BackgroundThe one-step membrane technique, using a human acellular dermal matrix (hADM), is an experimental method for treating large bone defects. This eliminates the need for the Masquelet membrane induction step, shortening the procedure while maintaining effectiveness. However, previous studies showed that colonizing hADM with bone marrow mononuclear cells (BMC) worsens healing, likely due to the presence of CD8+ lymphocytes, which negatively affect bone regeneration. This study aims to investigate whether the negative impact of BMC on bone healing in this technique is due to the CD8+ cell population.Materials and methodsA 5 mm femoral defect was created in 25 male Sprague-Dawley rats, divided into three groups (G1-G3). BMC were isolated from syngenic donor rats, with CD8+ lymphocytes removed magnetically from the BMC fraction in one group. The defects were filled with bone chips and wrapped with differently treated hADM: G1 received native hADM, G2 received hADM+BMC, and G3 received hADM+BMC-CD8. After 8 weeks, the femurs were evaluated through radiological, biomechanical, and histological examinations.ResultsBone defects and bone mineral density (BMD) were significantly improved in G3 (hADM+BMC-CD8) compared to G2 (hADM+BMC). Bone volume, bone formation, and median bending stiffness were higher in G3. Immunohistological analysis showed a significant decrease in CD8 cell count in G3, with a lower percentage of IFNγ-producing cells compared to G2.ConclusionDepleting CD8+ cells from BMC before colonizing hADM significantly improved bone healing, likely due to changes in the local mediator environment. This suggests that preoperative colonization with CD8+-depleted BMC could enhance the one-step membrane technique.

Ceramic additive manufacturing and microstructural analysis of tricalcium phosphate implants using X-ray microcomputed tomography

Additive manufacturing (AM) of ceramic bone implants from tricalcium phosphate (TCP) offers several benefits for bone regeneration and defect treatment. TCP scaffolds, e.g. featuring lattice or gyroid geometries, can effectively induce bone ingrowth and integration, showing a high potential in the treatment of large bone defects, e.g. as filler material for large bone defects. A major advantage of TCP is its osteoconductivity making it an effective choice for a broad range of orthopedic and dental applications. In addition, AM allows for the possibility to create precise, patient-specific implants with controllable mechanical properties. Those properties can be controlled by the implants' microstructure, e.g. in relation to bulk density and internal porosity. In this contribution, eleven resorbable bone implants were produced from β-tricalcium phosphate (β-TCP) in order to quantify the internal porosity in three dimensions using microcomputed tomography (μ CT). All components were manufactured using an extrusion-based process and scanned using an industrial μCT system at a voxel size of 10 μm. Two samples were physically prepared to allow a high-resolution μCT analysis at a voxel size of 1 μm. Results show that post-processed image data enables the non-destructive inspection of highly complex ceramic AM implants. Using μCT we were able to quantify internal porosity in β-TCP bone implant and quantify the geometry and distribution of wall thicknesses in the gyroid geometry. However, a detailed microstructural analysis is only possible using high-resolution μCT volume data, e.g. in relation to internal porosity. The findings emphasize that ceramic AM is able to produce complex components. However, NDT using μCT is crucial in the development of new materials and geometries. μCT provides high-resolution insights into the internal and external structure of ceramic AM components. It plays a critical role in detecting internal features, including small-scale porosity and delamination which are crucial for the integrity and functionality of medical implants. Moreover, μCT provides volumetric data that supports the design and manufacturing process at various stages, enabling an iterative approach of continuous improvement in mechanical performance and osseointegration.

Mild Thermotherapy-Assisted GelMA/HA/MPDA@Roxadustat 3D-Printed Scaffolds with Combined Angiogenesis-Osteogenesis Functions for Bone Regeneration.

Early reconstruction of the vascular network is a prerequisite to the effective treatment of substantial bone defects. Traditional 3D printed tissue engineering scaffolds designed to repair large bone defects do not effectively regenerate the vascular network, and rely only on the porous structure within the scaffold for nutrient transfer and metabolic waste removal. This leads to delayed bone restoration and hence functional recovery. Therefore, strategies for generation scaffolds with the capacity to efficiently regenerate vascularization should be developed. This study loads roxarestat (RD), which can stabilize HIF-1α expression in a normoxic environment, onto the mesopore polydopamine nanoparticles (MPDA@RD) to enhance the reconstruction of vascular network in large bone defects. Subsequently, MPDA@RD is mixed with GelMA/HA hydrogel bioink to fabricate a multifunctional hydrogel scaffold (GHM@RD) through 3D printing. In vitro results show that the GHM@RD scaffolds achieve good angiogenic-osteogenic coupling by activating the PI3K/AKT/HSP90 pathway in BMSCs and the PI3K/AKT/HIF-1α pathway in HUVECs under mild thermotherapy. In vivo experiments reveal that RD and mild hyperthermia synergistically induce early vascularization and bone regeneration of critical bone defects. In conclusion, the designed GHM@RD drug delivery scaffold with mild hyperthermia holds great therapeutic value for future treatment of large bone defects.

Fabrication of 3D printed trabecular bone-templated scaffolds modified with rare earth europium (III)-based complex for enhancing mitochondrial function in bone regeneration

Bone defects have been a tough clinical challenge. The natural trabecular tissue reflects a balance between the minimal metabolic cost of maintenance and maximal network stability, with mitochondria being the energy suppliers for osteogenesis. Herein, a 3D printed trabecular bone-templated scaffold composed of polylactide (PLA) modified with europium (III)-organic ligands (polydopamine and chitooligosaccharide, PDA/COS@Eu) was fabricated (denoted as Tra-PLA/PDA/COS@Eu) to augment bone repair by facilitating mitochondrial function. First, the trabecular bone templated-scaffold provides superior mechanical performance and permeability in contrast to a computer aided designed (CAD) scaffold under a same volume fraction. Tra-PLA/PDA/COS@Eu scaffold up regulated PI3K/AKT/S6K/HIF-1α pathway and significantly promoted BMSCs proliferation and osteogenic differentiation. In addition, Tra-PLA/PDA/COS@Eu scaffold provided anti-inflammatory environment by promoting macrophages M2 polarization through COS, and significantly stimulated BMSCs osteogenesis with enhanced mitochondrial function and biosynthesis. Remarkably, Eu ions are the key ingredient in enhancing mitochondrial function and biosynthesis in BMSCs. Further studies showed that the above-mentioned facilitations in a rabbit bone defect model were found to be more significant with trabecular bone-templated scaffolds, as opposed to CAD scaffolds. In summary, this novel trabecular bone-templated scaffold targeting mitochondrial function has the potential to become an effective method in the treatment of large bone defects.

Can locking plate fixation and free Vascularised fibular transfer with skin island achieve good functional outcome in the treatment of large bone defects of Tibia ? A study of 26 cases

BackgroundDespite the availability of multiple treatment options, management of tibial bone loss continues to be a challenge. Free vascularized fibula graft (FVFG) with a skin paddle offers better advantages over the other methods. We aimed to study the functional outcomes and QALY of patients with large tibial bone defects following FVFG with a locking plate. Materials and MethodsWe analyzed 26 consecutive patients with large tibial bone defects treated by free vascularized fibular graft (FVFG) and stabilization using a long locking plate between 2009 and 2018. All were followed up for a mean period of 42 months (24 to 120 months). Bony union, graft hypertrophy, and complications such as stress fracture and infections were assessed. Multivariate regression analysis was performed to identify any association between demographic factors, injury characteristics, treatment-related factors, and fibular hypertrophy. Additionally, The EQ-5D quality-of-life (QOL) indices were obtained using the SF-12 score to evaluate the patients' overall quality of life. ResultsThe mean age of the patients at the time of presentation was 36.26 yrs (range, 18–60 years). The cause of bone loss was open injury in 16 patients and infected nonunion in 10 patients. Complete union was achieved in 25 patients (96 %) without any requirement of additional surgical procedures. The mean union time of the graft was 4.04 months (range, 3–6 months). The mean fibular hypertrophy calculated by De Boer index was 0.61 %, 11 %, 28.24 % and 52.52 % at 3,6 months and 1 and 2 years respectively. Patients with metaphyseal bone loss have significant fibular hypertrophy. Participants in our study experienced a quality of life equivalent to 0.88 (range 0.79–0.99) of perfect health. ConclusionsFVFG with skin paddle and LCP fixation for massive tibial bone loss achieved satisfactory outcome and QALY even in the challenging healthcare environment of South India, a developing country.It maintains alignment, promotes graft hypertrophy, and prevents stress fractures. Level of evidenceLevel 4 Level of clinical careLevel I Tertiary trauma centre

Osteogenic Potential of a Biomaterial Enriched with Osteostatin and Mesenchymal Stem Cells in Osteoporotic Rabbits.

Mesoporous bioactive glasses (MBGs) of the SiO2-CaO-P2O5 system are biocompatible materials with a quick and effective in vitro and in vivo bioactive response. MBGs can be enhanced by including therapeutically active ions in their composition, by hosting osteogenic molecules within their mesopores, or by decorating their surfaces with mesenchymal stem cells (MSCs). In previous studies, our group showed that MBGs, ZnO-enriched and loaded with the osteogenic peptide osteostatin (OST), and MSCs exhibited osteogenic features under in vitro conditions. The aim of the present study was to evaluate bone repair capability after large bone defect treatment in distal femur osteoporotic rabbits using MBGs (76%SiO2-15%CaO-5%P2O5-4%ZnO (mol-%)) before and after loading with OST and MSCs from a donor rabbit. MSCs presence and/or OST in scaffolds significantly improved bone repair capacity at 6 and 12 weeks, as confirmed by variations observed in trabecular and cortical bone parameters obtained by micro-CT as well as histological analysis results. A greater effect was observed when OST and MSCs were combined. These findings may indicate the great potential for treating critical bone defects by combining MBGs with MSCs and osteogenic peptides such as OST, with good prospects for translation to clinical practice.

A coaxial electrospun mat coupled with piezoelectric stimulation and atorvastatin for rapid vascularized bone regeneration.

The repair of critical bone defects caused by various clinical conditions needs to be addressed urgently, and the regeneration of large bone defects depends on early vascularization. Therefore, enhanced vascularization of artificial bone grafts may be a promising strategy for the regeneration of critical-sized bone defects. Taking into account the importance of rapid angiogenesis during bone repair and the potential of piezoelectric stimulation in promoting bone regeneration, novel coaxial electrospun mats coupled with piezoelectric materials and angiogenic drugs were fabricated in this study using coaxial electrospinning technology, with a shell layer loaded with atorvastatin (AVT) and a core layer loaded with zinc oxide (ZnO). AVT was used as an angiogenesis inducer, and piezoelectric stimulation generated by the zinc oxide was used as an osteogenesis enhancer. The multifunctional mats were characterized in terms of morphology, core-shell structure, piezoelectric properties, drug release, and mechanical properties, and their osteogenic and angiogenic capabilities were validated in vivo and ex vivo. The results revealed that the coaxial electrospun mats exhibit a porous surface morphology and nanofibers with a core-shell structure, and the piezoelectricity of the mats improved with increasing ZnO content. Excellent biocompatibility, hydrophilicity and cell adhesion were observed in the multifunctional mats. Early and rapid release of AVT in the fibrous shell layer of the mat promoted angiogenesis in human umbilical vascular endothelial cells (HUVECs), whereas ZnO in the fibrous core layer harvested bioenergy and converted it into electrical energy to enhance osteogenic differentiation of rat bone mesenchymal stem cells (BMSCs), and both modalities synergistically promoted osteogenesis and angiogenesis. Furthermore, optimal bone regeneration was achieved in a model of critical bone defects in the rat mandible. This osteogenesis-promoting effect was induced by electrical stimulation via activation of the calcium signaling pathway. This multifunctional mat coupling piezoelectric stimulation and atorvastatin promotes angiogenesis and bone regeneration, and shows great potential in the treatment of large bone defects.

Evaluation of post-extraction alveolar regeneration time in advanced periodontal disease employing novel hydroxyapatitepolymeric (FlexiOss®Vet) in dogs.

The purpose of the study was to demonstrate bone regeneration and the time of formation of new alveolar bone based on implanted FlexiOss®Vet bone substitute material. The study attempted to determine the time taken to fill bone defects with newly formed osseous bone compared to alveoli with a standard method of filling the post-extraction alveolus with a collagen sponge. The study was conducted on a group of 12 dogs with advanced periodontal disease (stage IV) in which polymeric hydroxyapatite bone substitute material (FlexiOss®Vet) was implanted into alveoli on the right side, and collagen sponge was implanted into alveoli on the left side in the same patient. The patients underwent macroscopic inspection and X-ray examination at different periods of regeneration after the procedure. On the right side, macroscopically, the alveoli showed features of marked enlargement, and on X-ray examination they gave opacity to X-rays and there was no clear border between the alveolus and alveolar bone. On the left side, the alveoli were clearly penetrable to X-rays, and hollow alveoli filled mainly with connective tissue were observed. The study also showed a significant reduction in bone healing time in alveoli with implants compared to self-healing alveoli. These results suggest that the implanted material is significantly beneficial in the process of bone regeneration in large bone defects in dogs and notably shortens the process of bone regeneration after tooth extractions. It is presumed that this could reflect a model for the treatment of large bone defects in not only the maxilla and mandible, but also long bones, and that it could be a model for alveolar healing in humans.

Docking site complications analysis of Ilizarov bone transport technique in the treatment of tibial bone defects

BackgroundTreating long bone defects of the extremities caused by trauma, infection, tumours, and nonunion has been challenging for clinical orthopaedic surgeons. Bone transport techniques have the potential to treat bone defects. However, inevitable docking site complications related to bone transport techniques have been reported in many studies. The purpose of this study was to investigate the risk factors associated with docking site complications in patients who underwent the Ilizarov bone transport technique for the treatment of tibial bone defects.MethodsThis retrospective study included 103 patients who underwent bone transport for the treatment of large bone defects in the tibia from October 2012 to October 2019. Patient demographic data, complications and clinical outcomes after a minimum of 2 years of follow-up were collected and retrospectively analysed. Additionally, univariate analysis and logistic regression analysis were used to analyse the factors that may affect the development of docking site complications in patients with tibial bone defects treated with the Ilizarov bone transport technique. The clinical outcomes were evaluated using the Association for the Study and Application of the Ilizarov criteria (ASAMI) at the last clinical follow-up.ResultsAll 103 patients with an average follow-up of 27.5 months. The docking site complications rate per patient was 0.53, and delayed union occurred in 22 cases (21.4%), axial deviation occurred in 19 cases (18.4%) and soft tissue incarceration occurred in 10 cases (9.7%). According to the results of the logistic regression analysis, the bone defect length (P = 0.001, OR = 1.976), and bone defect of distal 1/3 (P = 0.01, OR = 1.976) were significantly correlated with delayed union. Bone defect length (P < 0.001, OR = 1.981) and external fixation time (P = 0.012, OR = 1.017) were significantly correlated with axial deviation. Soft tissue defects (P = 0.047, OR = 6.766) and the number of previous operations (P = 0.001, OR = 2.920) were significantly correlated with soft tissue incarceration. The ASAMI bone score at the last follow-up showed a rate of excellent and good bone results of 95.1% and a rate of excellent functional results of 90.3%.ConclusionThe Ilizarov bone transport technique is a practical and effective method for the treatment of tibial bone defects. However, the incidence of complications at the docking site is high, of which bone defect length, external fixation time, the number of previous operations, soft tissue defects and the bone defect of distal 1/3 are statistically significantly associated with the occurrence of docking site complications.

Accelerated bone defect repairment by carbon nitride photoelectric conversion material in core–shell nanofibrous depended on neurogenesis

Highly efficient bone repair materials are essential for the clinical treatment of large bone defects. This study aimed to develop nanofibrous scaffolds for bone defect repairment. Here, we reported that insulin like growth factor (IGF) adsorbed into phosphorus doped graphite phase carbon nitride (C3N4(P)) as core, and nerve growth factor (NGF) adsorbed into silk fibroin (SF) as shell to prepare nanofibrous scaffolds (IGF@C3N4(P)/NGF@SF) by coaxial electrospining for accelerating bone formation. Additionally, C3N4(P) was employed as a photoelectric conversion material capable of achieving the mutual conversion of light and electricity. Remarkably, we found that red light + IGF@C3N4(P)/NGF@SF scaffold may enhance osteogenesis in bone mesenchymal stem cells (BMSCs) by activating the extracellular regulated protein kinases1/2 (Erk1/2), which subsequently activated runt-related transcription factor 2 (Runx2) and the mammalian target of rapamycin (mTOR) pathway. Consequently, the mRNA expression levels of downstream osteogenic related genes were increased. Furthermore, we observed that red light + IGF@C3N4(P)/NGF@SF scaffold promoted BMSCs induced neural differentiation cells differentiated into neuron and upregulated the mRNA expression levels of neuron specific related genes. Interestingly, we also demonstrated the formation of new neurons in the Haversian canal within the cranial defect area in mice, indicating that red light + IGF@C3N4(P)/NGF@SF scaffold promoted osteogenesis with neurogenesis. Moreover, our RNA sequencing results supported the activation of neurogenesis along with osteogenesis. Based on these novel findings, we conclude that red light + IGF@C3N4(P)/NGF@SF scaffold exhibits great potential as a prospective biomaterial for promoting bone defect repairment with neurogenesis, and the utilization of red light is crucial in facilitating this process.

Cold physical plasma treatment optimization for improved bone allograft processing.

In musculoskeletal surgery, the treatment of large bone defects is challenging and can require the use of bone graft substitutes to restore mechanical stability and promote host-mediated regeneration. The use of bone allografts is well-established in many bone regenerative procedures, but is associated with low rates of ingrowth due to pre-therapeutic graft processing. Cold physical plasma (CPP), a partially ionized gas that simultaneously generates reactive oxygen (O2) and nitrogen (N2) species, is suggested to be advantageous in biomedical implant processing. CPP is a promising tool in allograft processing for improving surface characteristics of bone allografts towards enhanced cellularization and osteoconduction. However, a preclinical assessment regarding the feasibility of pre-therapeutic processing of allogeneic bone grafts with CPP has not yet been performed. Thus, this pilot study aimed to analyze the bone morphology of CPP processed allografts using synchrotron radiation-based microcomputed tomography (SR-µCT) and to analyze the effects of CPP processing on human bone cell viability and function. The analyzes, including co-registration of pre- and post-treatment SR-µCT scans, revealed that the main bone morphological properties (total volume, mineralized volume, surface area, and porosity) remained unaffected by CPP treatment if compared to allografts not treated with CPP. Varying effects on cellular metabolic activity and alkaline phosphatase activity were found in response to different gas mixtures and treatment durations employed for CPP application. It was found that 3min CPP treatment using a He + 0.1% N2 gas mixture led to the most favourable outcome regarding a significant increase in bone cell viability and alkaline phosphatase activity. This study highlights the promising potential of pre-therapeuthic bone allograft processing by CPP prior to intraoperative application and emphasizes the need for gas source and treatment time optimization for specific applications.

Osteoinductive intramedullary implant as an adjunctive therapy for bone transport: A promising approach to accelerate bone defect healing

A recent study published in Nature Communications presents a unique approach using an osteoinductive intramedullary (IM) implant as an adjunctive therapy for bone transport distraction osteogenesis. The study demonstrates that this innovative technique achieves early bony bridging, eliminates pin tract infections, and prevents docking site non-union, offering significant potential for the treatment of large bone defects. The study also highlights an additive effect of the osteoinductive IM implant on distraction osteogenesis for managing bone defect.

Silicone rubber sealed channel induced self-healing of large bone defects: Where is the limit of self-healing of bone?

BackgroundLarge defects of long tubular bones due to severe trauma, bone tumor resection, or osteomyelitis debridement are challenging in orthopedics. Bone non-union and other complications often lead to serious consequences. At present, autologous bone graft is still the gold standard for the treatment of large bone defects. However, autologous bone graft sources are limited. Silicon rubber (SR) materials are widely used in biomedical fields, due to their safety and biocompatibility, and even shown to induce nerve regeneration. Materials and methodsWe extracted rat bone marrow mesenchymal stem cells (BMMSCs) in vitro and verified the biocompatibility of silicone rubber through cell experiments. Then we designed a rabbit radius critical sized bone defect model to verify the effect of silicone rubber sealed channel inducing bone repair in vivo. ResultsSR sealed channel could prevent the fibrous tissue from entering the fracture end and forming bone nonunion, thereby inducing self-healing of long tubular bone through endochondral osteogenesis. The hematoma tissue formed in the early stage was rich in osteogenesis and angiogenesis related proteins, and gradually turned into vascularization and endochondral osteogenesis, and finally realized bone regeneration. ConclusionsIn summary, our study proved that SR sealed channel could prevent the fibrous tissue from entering the fracture end and induce self-healing of long tubular bone through endochondral osteogenesis. In this process, the sealed environment provided by the SR channel was key, and this might indicate that the limit of self-healing of bone exceeded the previously thought. The translational potential of this articleThis study investigated a new concept to induce the self-healing of large bone defects. It could avoid trauma caused by autologous bone extraction and possible rejection reactions caused by bone graft materials. Further research based on this study, including the innovation of induction materials, might invent a new type of bone inducing production, which could bring convenience to patients. We believed that this study had significant meaning for the treatment of large bone defects in clinical practice.

Microenvironment-targeted strategy steers advanced bone regeneration.

Treatment of large bone defects represents a great challenge in orthopedic and craniomaxillofacial surgery. Traditional strategies in bone tissue engineering have focused primarily on mimicking the extracellular matrix (ECM) of bone in terms of structure and composition. However, the synergistic effects of other cues from the microenvironment during bone regeneration are often neglected. The bone microenvironment is a sophisticated system that includes physiological (e.g., neighboring cells such as macrophages), chemical (e.g., oxygen, pH), and physical factors (e.g., mechanics, acoustics) that dynamically interact with each other. Microenvironment-targeted strategies are increasingly recognized as crucial for successful bone regeneration and offer promising solutions for advancing bone tissue engineering. This review provides a comprehensive overview of current microenvironment-targeted strategies and challenges for bone regeneration and further outlines prospective directions of the approaches in construction of bone organoids.

Research Progress of Bone Implant Additive Manufacturing

Bone implants are currently a solution for the treatment of large bone defects. The structural design and manufacture of complex bone tissue engineering scaffolds can be realized by using additive manufacturing technology. Advances in additive manufacturing techniques and the continued emergence of related materials provide different opportunities for new bone implant techniques to achieve the challenging requirements of proposed bone implants. The purpose of this review is to present the current status and analyze the advantages and disadvantages of various additive manufacturing for the manufacturing of bone implants. Five different manufacturing techniques (multilayer deposition forming, ink direct writing, laser melting, laser sintering, and light curing are reviewed.) and the currently required bone implants technology, and thus put forward the research and development direction of additive manufacturing suitable for bone implants.

Development of a novel thermogelling PEC-based ECM mimicking nanocomposite bioink for bone tissue engineering

Non-union of large bone defects has been an existing clinical problem. 3D extrusion-based bioprinting provides an efficient approach to tackle such problems. This approach enables the use of various biomaterials, cell types and growth factors in developing a superior bone graft that is specific to the defect. In this article, we have designed and printed an ECM mimicking, self-assembled polyelectrolyte complex (PEC) based fibrous bioink using natural polymers like chitosan-polygalacturonic acid (PGA) and other biomaterials – gelatin, laponite and nanohydroxyapatite with a modified 3D printer. The developed bioink possesses a thermo-reversible sol-gel transition at physiological pH and temperature. Here, we demonstrated that post-printing, our fiber-reinforced bioink had significant cell proliferation with cell viability of >80% and negligible cell morbidity. The practicability of developing this self-assembled PEC-based bioink was assessed. Bioink with 4% gelatin (PECHLG4) had optimal printability with a minimal swelling ratio of approximately 3%. The printed scaffold had integrity for a period of 8 days under 0.5 mg/mL lysozyme concentration. We also evaluated the mechanical property of the bioink using compression analysis which gave an elastic modulus of 16 KPa. This combination of natural polymers and nanocomposite, along with a fibrous network of PECs, is itself a novel approach for 3D bioprinting and can be a preliminary proposition for the treatment of large bone defects.

Spatiotemporalized Hydrogel Microspheres Promote Vascularized Osteogenesis via Ultrasound Oxygen Delivery

AbstractDisturbance of spatiotemporal oxygen balance is the main cause of delayed healing or nonhealing of large bone defects. The accurate administration of oxygen to regulate disruptions in the spatiotemporal oxygen equilibrium during 9 h of hypoxia is imperative for bone tissue regeneration. Herein, oxygen‐loaded nanobubbles prepared by double emulsification are successfully embedded in GelMA/HepMA microsphere macromolecular meshwork by microfluidic techniques, and a spatiotemporalized hydrogel microsphere is constructed by noncovalently binding bone morphogenetic protein 2 (BMP‐2). The spatiotemporalized hydrogel microspheres precisely “remote control” oxygen release by ultrasound in vitro 9 h after bone injury to regulate spatiotemporal oxygen homeostasis disorder, maintain a high level of vascular endothelial growth factor (VEGF) expression, and accelerate bone repair. The spatiotemporalized hydrogel microspheres possess good oxygen‐carrying capacity and ultrasonic responsiveness, and the oxygen concentration increases to 1.63, 1.95, 2.11, and 2.29 times under the ultrasound action at different intensities of 1, 2, 3, and 4 W, respectively, providing the conditions for the precise regulation of spatiotemporal oxygen balance disorder by ultrasound. In the in vitro hypoxia model and in vivo rat femoral defect model, the spatiotemporal hydrogel microspheres show good vascularization and osteogenesis capabilities, which provide a new strategy for the clinical treatment of large bone defects.

An osteoinductive and biodegradable intramedullary implant accelerates bone healing and mitigates complications of bone transport in male rats.

Bone transport is a surgery-driven procedure for the treatment of large bone defects. However, challenging complications include prolonged consolidation, docking site nonunion and pin tract infection. Here, we develop an osteoinductive and biodegradable intramedullary implant by a hybrid tissue engineering construct technique to enable sustained delivery of bone morphogenetic protein-2 as an adjunctive therapy. In a male rat bone transport model, the eluting bone morphogenetic protein-2 from the implants accelerates bone formation and remodeling, leading to early bony fusion as shown by imaging, mechanical testing, histological analysis, and microarray assays. Moreover, no pin tract infection but tight osseointegration are observed. In contrast, conventional treatments show higher proportion of docking site nonunion and pin tract infection. The findings of this study demonstrate that the novel intramedullary implant holds great promise for advancing bone transport techniques by promoting bone regeneration and reducing complications in the treatment of bone defects.

Combination therapy with BMSCs‑exosomes and porous tantalum for the repair of femur supracondylar defects.

In the field of orthopedics, defects in large bones have proven challenging to resolve. The aim of the present study was to address this problem through the combination of tantalum metal (pTa) with exosomes derived from bone marrow mesenchymal stem cells (BMSCs), which have the potential to enhance regeneration of full thickness femoral bone defects in rats. Cell culture results demonstrated that exosomes improved the proliferation and differentiation of BMSCs. Following establishment of a supracondylar femoral bone defect, exosomes and pTa were implanted into the defect area. Results demonstrated that pTa acts as a core scaffold for cell adhesion and exhibits good biocompatibility. Moreover, micro‑CT scan results as well as histological examination demonstrated that pTa had a significant effect on osteogenesis, with the addition of exosomes further promoting bone tissue regeneration and repair. In conclusion, this novel composite scaffold can effectively promote bone regeneration in large bone defect areas, providing a new approach for the treatment of large bone defects.

One Stage Masquelets Technique: Evaluation of Different Forms of Membrane Filling with and without Bone Marrow Mononuclear Cells (BMC) in Large Femoral Bone Defects in Rats.

The classic two-stage masquelet technique is an effective procedure for the treatment of large bone defects. Our group recently showed that one surgery could be saved by using a decellularized dermis membrane (DCD, Epiflex, DIZG). In addition, studies with bone substitute materials for defect filling show that it also appears possible to dispense with the removal of syngeneic cancellous bone (SCB), which is fraught with complications. The focus of this work was to clarify whether the SCB can be replaced by the granular demineralized bone matrix (g-DBM) or fibrous demineralized bone matrix (f-DBM) demineralized bone matrix and whether the colonization of the DCD and/or the DBM defect filling with bone marrow mononuclear cells (BMC) can lead to improved bone healing. In 100 Sprague Dawley rats, a critical femoral bone defect 5 mm in length was stabilized with a plate and then encased in DCD. Subsequently, the defect was filled with SCB (control), g-DBM, or f-DBM, with or without BMC. After 8 weeks, the femurs were harvested and subjected to histological, radiological, and biomechanical analysis. The analyses showed the incipient bony bridging of the defect zone in both groups for g-DBM and f-DBM. Stability and bone formation were not affected compared to the control group. The addition of BMCs showed no further improvement in bone healing. In conclusion, DBM offers a new perspective on defect filling; however, the addition of BMC did not lead to better results.