Bone Fracture Repair Research Articles

Fracture repair by IOX2: Regulation of the hypoxia inducible factor-1α signaling pathway and BMSCs

The treatment of fracture delayed union and nonunion has become a challenging problem. Hypoxia inducible factor-1α (HIF-1α) is reported to be a key factor in fracture healing, and is degraded by hydroxylation of prolyl hydroxylase (PHDs) under normal oxygen. Small molecules could inhibit the activity of PHDs, stabilize HIF-1α protein, regulate the expression of downstream target genes of HIF-1α, and make the body adapt to hypoxia. The migration and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is the most promising candidate for the treatment of fracture nonunion. Here we reported that IOX2, an HIF-1α PHD inhibitor, markedly improved the proliferation and migration of BMSCs by upregulating intracellular Ca2+ and concomitant decreasing reactive oxygen species (ROS) in vitro, and facilitated the repair of bone fracture by increasing the number of BMSCs and cartilage formation in vivo. No significant influence of IOX2 on the proliferation and migration of BMSCs after silencing of the HIF-1α. Together, our findings indicated that IOX2 promoted the proliferation and migration of BMSCs via the HIF-1α pathway and further accelerated fracture healing. These results provide a deeper understanding of the mechanism by which HIF promotes fracture healing.

Constructions of ROS-responsive titanium-hydroxyapatite implant for mesenchymal stem cell recruitment in peri-implant space and bone formation in osteoporosis microenvironment.

To solve the issue of unsatisfactory recruitment of mesenchymal stem cells (MSCs) around implant in osteoporotic fractures, we fabricated a ROS-responsive system on titanium surface through hydroxyapatite coating and biomolecule grafting. The porous hydroxyapatite and phosphorylated osteogenic growth peptides (p-OGP) were introduced onto titanium surface to synergistically improve osteogenic differentiation of MSCs. After the p-OGP-promoted expression of osteogenic related proteins, the calcium and phosphate ions were released through the degradation of hydroxyapatite and integrated into bone tissues to boost the mineralization of bone matrix. The ROS-triggered release of DNA aptamer (Apt) 19S in the osteoporotic microenvironment guides MSC migration to implant site due to its high affinity with alkaline phosphatase on the membrane of MSCs. Once MSCs reached the implant interface, their osteogenic differentiation potential was enhanced by p-OGP and hydroxyapatite to promote bone regeneration. The study here provided a simple and novel strategy to prepare functional titanium implants for osteoporotic bone fracture repair.

Targeted activation of androgen receptor signaling in the periosteum improves bone fracture repair

Low testosterone level is an independent predictor of osteoporotic fracture in elderly men as well as increased fracture risk in men undergoing androgen deprivation. Androgens and androgen receptor (AR) actions are essential for bone development and homeostasis but their linkage to fracture repair remains unclear. Here we found that AR is highly expressed in the periosteum cells and is co-localized with a mesenchymal progenitor cell marker, paired-related homeobox protein 1 (Prrx1), during bone fracture repair. Mice lacking the AR gene in the periosteum expressing Prrx1-cre (AR-/Y;Prrx1::Cre) but not in the chondrocytes (AR-/Y;Col-2::Cre) exhibits reduced callus size and new bone volume. Gene expression data analysis revealed that the expression of several collagens, integrins and cell adhesion molecules were downregulated in periosteum-derived progenitor cells (PDCs) from AR-/Y;Prrx1::Cre mice. Mechanistically, androgens-AR signaling activates the AR/ARA55/FAK complex and induces the collagen-integrin α2β1 gene expression that is required for promoting the AR-mediated PDCs migration. Using mouse cortical-defect and femoral graft transplantation models, we proved that elimination of AR in periosteum of host mice impairs fracture healing, regardless of AR existence of transplanted donor graft. While testosterone implanted scaffolds failed to complete callus bridging across the fracture gap in AR-/Y;Prrx1::Cre mice, cell-based transplantation using DPCs re-expressing AR could lead to rescue bone repair. In conclusion, targeting androgen/AR axis in the periosteum may provide a novel therapy approach to improve fracture healing.

PDGFR\u03b1 reporter activity identifies periosteal progenitor cells critical for bone formation and fracture repair

The outer coverings of the skeleton, which is also known as the periosteum, are arranged in concentric layers and act as a reservoir for tissue-specific bone progenitors. The cellular heterogeneity within this tissue depot is being increasingly recognized. Here, inducible PDGFRα reporter animals were found to mark a population of cells within the periosteum that act as a stem cell reservoir for periosteal appositional bone formation and fracture repair. During these processes, PDGFRα reporter+ progenitors give rise to Nestin+ periosteal cells before becoming osteoblasts and osteocytes. The diphtheria toxin-mediated ablation of PDGFRα reporter+ cells led to deficits in cortical bone formation during homeostasis and a diminutive hard callus during fracture repair. After ossicle transplantation, both mouse PDGFRα reporter+ periosteal cells and human Pdgfrα+ periosteal progenitors expand, ossify, and recruit marrow to a greater extent than their counterpart periosteal cells, whereas PDGFRα reporter− periosteal cells exhibit a predisposition to chondrogenesis in vitro. Total RNA sequencing identified enrichment of the secreted factors Fermt3 and Ptpn6 within PDGFRα reporter+ periosteal cells, which partly underlie the osteoblastogenic features of this cell population.

Construction of the miRNA–mRNA regulatory networks for both the cartilage formation and remodel zones in the antler tip in sika deer (

Context Deer antlers offer a premium model for investigating the mechanisms underlying arguably the most rapid cartilage formation and remodelling system. Although the cartilage formation process in the antler has been relatively intensively studied, thus far, at a molecular level, the cartilage remodelling has essentially been untouched. Aims To construct miRNA–mRNA regulatory networks for both the cartilage formation and remodel zones in the antler tip. Methods The tissues from both the cartilage formation zone (FZ) and remodel zone (RZ) in rapid growing antlers of sika deer were sampled, profiles of both mRNA and miRNA from these samples were sequenced and analysed, miRNA–mRNA regulatory networks for these two zones were constructed, and their encoded/targeted differentially expressed genes (DEGs) were identified through bioinformatics analysis. Key results In total, 3703 DEGs in the FZ over the RZ were identified, with 1615 being upregulated and 2088 downregulated. The upregulated DEGs in the FZ were found to be mainly enriched in cell proliferation and chondrogenesis/osteogenesis, whereas those in the RZ were enriched in the formation of chondroclasts and osteoclasts. In total, 308 unique mature miRNAs were detected including 110 significantly differentially expressed miRNAs. These miRNAs are predicted to target extracellular matrix proteins, growth factors and receptors, and transcriptional factors, all related to cartilage formation and remodelling. To verify the reliability of our datasets, we successfully tested the regulatory function of one of the top 10 hub miRNAs, miR-155, in vitro. Conclusions The miRNA–mRNA regulatory networks for cartilage formation zone (FZ) in relation to cartilage remodel zone (RZ) were successfully constructed, and validated, which has laid the foundation for the identification of potent growth factors and novel regulation system in bone formation through endochondral ossification. Implications We believe that our datasets are reliable for further mining potent growth factors and novel regulation systems for rapid cartilage formation, remodelling and bone fracture repair by using this unique model, the deer antler.

Evaluation of serum calcium, phosphorus and alkaline phosphatase levels during long bone fracture repair in dogs stabilized with string of pearls plating technique

The present study was conducted to evaluate biochemical parameters like serum calcium, phosphorus and alkaline phosphatase during long bones fracture healing in six dogs, which were stabilized with string of pearls (SOP) plate. Statistical analysis revealed no significant variation (P<0.05) in these parameters during the entire period of healing and the values were within the normal range.

Conventional bone plating versus minimally invasive plate osteosynthesis (MIPO) for repair of long bone fracture in dogs

Conventional bone plating versus minimally invasive plate osteosynthesis (MIPO) for repair of long bone fracture in dogs

CXCR4 Mediates the Effects of IGF-1R Signaling in Rodent Bone Homeostasis and Fracture Repair

CXCR4 Mediates the Effects of IGF-1R Signaling in Rodent Bone Homeostasis and Fracture Repair

Comprehensive review of the incisive branch of the inferior alveolar nerve.

The incisive branch of the inferior alveolar nerve is a vital anatomical structure within the anterior mandible that has not been thoroughly defined and outlined in reports in the literature until recent years. Advances in radiological imaging, particularly the widespread use of cone-beam computed tomography has allowed for accurate visualization of the mandibular incisive canal (MIC) and its associated incisive branch of the inferior alveolar nerve. Surgical damage to the MIC, which could result in hemorrhage and sensory disturbance, may occur in commonly practiced oral and maxillofacial procedures, such as chin bone harvesting, implant placement, fracture repair and removal of pathologic entities of the anterior mandible. Knowledge of both the presence, dimensions and location of the incisive branch is a vital component to pre and peri-operative planning of oral and maxillofacial surgeries performed within the mandible, particularly within the interforaminal zone. In this article, the terminology, anatomy, imaging, surgical consideration, and pathology of the incisive branch will be discussed.

Accessory carpal bone fracture repair by means of computer‐assisted orthopaedic surgery in a Warmblood stallion

SummaryA 10‐year‐old, 595 kg Irish Warmblood stallion used for showjumping was presented with a marked right forelimb lameness at walk. The horse sustained a dorsal plane fracture of the accessory carpal bone (ACB) when falling with both carpi in flexion. The fracture was repaired by means of computer‐assisted orthopaedic surgery (CAOS) using two cortex screws placed in lag fashion. In a second CAOS procedure, a dorsoproximal fragment of the ACB was removed after further proximal displacement had become apparent. Both surgical procedures were facilitated by the application of a fibreglass cast to immobilise the carpus in extension and to allow for the placement of the patient tracker distant from the surgical site. One year after surgery, the horse had returned to full athletic activity. Neither the antebrachiocarpal joint nor the carpal sheath were distended. Control radiographs and standing cone beam computed tomography showed complete osseous union of the fracture and osteophyte formation on the caudal aspect of the radius and the proximal border of the ACB.

Exosomal PD-L1 induces osteogenic differentiation and promotes fracture healing by acting as an immunosuppressant

A moderate inflammatory response at the early stages of fracture healing is necessary for callus formation. Over-active and continuous inflammation, however, impairs fracture healing and leads to excessive tissue damage. Adequate fracture healing could be promoted through suppression of local over-active immune cells in the fracture site. In the present study, we achieved an enriched concentration of PD-L1 from exosomes (Exos) of a genetically engineered Human Umbilical Vein Endothelial Cell (HUVECs), and demonstrated that exosomes overexpressing PD-L1 specifically bind to PD-1 on the T cell surface, suppressing the activation of T cells. Furthermore, exosomal PD-L1 induced Mesenchymal Stem Cells (MSCs) towards osteogenic differentiation when pre-cultured with T cells. Moreover, embedding of Exos into an injectable hydrogel allowed Exos delivery to the surrounding microenvironment in a time-released manner. Additionally, exosomal PD-L1, embedded in a hydrogel, markedly promoted callus formation and fracture healing in a murine model at the early over-active inflammation phase. Importantly, our results suggested that activation of T cells in the peripheral lymphatic tissues was inhibited after local administration of PD-L1-enriched Exos to the fracture sites, while T cells in distant immune organs such as the spleen were not affected. In summary, this study provides the first example of using PD-L1-enriched Exos for bone fracture repair, and highlights the potential of Hydrogel@Exos systems for bone fracture therapy through immune inhibitory effects.

Development of Injectable Hydroxyapatite/2-(dimethylamino)Ethyl Methacrylate/Polyvinylpyrrolidone Aqua-Hydrogel System to Repair of the Shoulder Joint Head for Hemiarthroplasty.

This study aimed to develop osteogenic structure assembly for modular bone treatment presentations, effect of 2-(dimethylamino)ethyl methacrylate and polyvinyl pyrrolidone combination as cell adhesive molecule with hydroxyapatite-based composite as osteoconductive constituent was inspected on bone fracture repair. The prepared injectable composite hydrogel showed significantly improved mechanical stability. The ternary composite gel was characterized for functional group modifications and chemical interactions using Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). Moreover, X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) analyses were performed to observe surface appearances of the hydrogel. The hydroxyapatite/2-(dimethylamino)ethyl methacrylate/poly-N-vinyl-2-pyrrolidone hydrogel played key role in supporting osteoblastic cell spread due to their bioactivity and strength abilities. The present findings revealed the significance of hydroxyapatite concentration on proliferation and osteogenic purpose of the cells. The developed performances of hydrogel have been improved cell proliferation and functions to repair bone fracture.

Multi-ion-doped nano-hydroxyapatite-coated titanium intramedullary pins for long bone fracture repair in dogs-Clinical evaluation.

Plasma spray nano-hydroxyapatite-coated titanium intramedullary implants doped either with 5% zinc, 2.5% strontium, and 2.5% fluorine ions or with 5% zinc, 5% strontium, and 2.5% silver ions were evaluated compared with plasma spray nano-hydroxyapatite-coated titanium intramedullary implant and uncoated titanium intramedullary implants for open reduction and internal immobilization in 24 clinical cases of long bone fracture repair in dogs. Fracture-healing limb outcome was evaluated clinically, that is, radiographically. Biochemical estimation of serum calcium, serum phosphorus, alkaline phosphatase (ALP), and bone markers (bone ALP [BALP] and C-telopeptide of type 1 collagen [CTX]) was carried out on 0th day, 3rd week, 6th, and 9th week postoperatively. Multi-ion-doped plasma spray nano-hydroxyapatite-coated titanium intramedullary implants were found to be superior to plasma spray nano-hydroxyapatite-coated titanium intramedullary implants and uncoated titanium intramedullary implants in terms of all the parameters studied. Using plasma spray nano-hydroxyapatite-coated titanium implants doped with multi ions, that is, 5% zinc, 5% strontium, and 2.5% silver gave the best results in fracture repair followed by the implants doped with 5% zinc, 2.5% strontium, and 2.5% fluorine ions. Earliest and excellent limb usage with no postoperative complications was the hallmark of the use of these multi-ion-doped implants with higher serum calcium, serum phosphorus, ALP, BALP, and CTX values up to 3rd postoperative week and no lameness on the 21st day.

Histone Demethylase KDM5C Deficiency Inhibits Bone Formation and Fracture Healing in Aged Mice by Epigenetically Activating Erdr1

Background: Fractures are one of the most common clinical injuries, especially for elders with osteoporosis. KDM5C specifically demethylate di- and tri-methylated lysine 4 on histone. It is frequently mutated in X-linked intellectual disability patients exhibiting physical and behavioral abnormalities. However, it is unclear whether KDM5C plays a role in bone formation and fracture repair. Methods: We used KDM5C conventional knockout mice model to investigate its role on bone formation. Western blotting, immunofluorescence staining, RNAseq, and ChIP assay were applied to demonstrate the molecular mechanism. Open femur fracture model was used to investigate the effects of KDM5C and Erdr1 on fracture healing. Findings: We found that the expression level of KDM5C was constantly increased during the osteogenesis of MSCs. Silencing endogenous KDM5C inhibited osteogenic differentiation of MSCs in vitro and KDM5C knockout mice displayed decreased bone mass and abnormal bone development. Further, RNA-seq analysis showed that PI3K-Akt signaling pathway and Erdr1 were most significantly influenced by KDM5C. KDM5C deficiency resulted in increased Erdr1 expression by histone modification. While knockdown of Erdr1 could promote osteogenesis and angiogenesis. Finally, using an experimental mouse femur fracture model, we found that KDM5C deficiency would impair fracture healing, which could be rescued by silencing Erdr1. More importantly, we found that KDM5C was decreased in bone samples of osteoporotic fracture. Interpretation: Taken together, these results showed that KDM5C was a novel regulator of osteogenesis and angiogenesis. KDM5C or Erdr1 might be potential therapeutic targets for the treatment of fracture and other bone diseases. Funding: The work was supported by grants from the National Natural Science Foundation of China (NSFC No. 81871778). Declaration of Interest: The authors declare that they have no conflict of interest. Ethical Approval: All surgical interventions, treatments and postoperative animal care procedures were strictly performed in accordance with the guidelines for Animal Welfare and Ethics Committee of Guangzhou University of Chinese medicine. Human bone tissues were obtained in the Second Affiliated Hospital of Guangzhou Medical University. All animal experiments were performed in accordance with protocols that were approved and authorized by the Animal Welfare and Ethics Committee of Guangzhou University of Chinese medicine.

Bone-Forming Peptide-4 Induces Osteogenic Differentiation and VEGF Expression on Multipotent Bone Marrow Stromal Cells.

Bone morphogenetic proteins (BMPs) have been widely used as treatment for bone repair. However, clinical trials on fracture repair have challenged the effectiveness of BMPs and suggested that delivery of multipotent bone marrow stromal cells (BMSCs) might be beneficial. During bone remodeling and bone fracture repair, multipotent BMSCs differentiate into osteoblasts or chondrocytes to stimulate bone formation and regeneration. Stem cell-based therapies provide a promising approach for bone formation. Extensive research has attempted to develop adjuvants as specific stimulators of bone formation for therapeutic use in patients with bone resorption. We previously reported for the first time bone-forming peptides (BFPs) that induce osteogenesis and bone formation. BFPs are also a promising osteogenic factor for prompting bone regeneration and formation. Thus, the aim of the present study was to investigate the underlying mechanism of a new BFP-4 (FFKATEVHFRSIRST) in osteogenic differentiation and bone formation. This study reports that BFP-4 induces stronger osteogenic differentiation of BMSCs than BMP-7. BFP-4 also induces ALP activity, calcium concentration, and osteogenic factors (Runx2 and osteocalcin) in a dose dependent manner in BMSCs. Therefore, these results indicate that BFP-4 can induce osteogenic differentiation and bone formation. Thus, treatment of multipotent BMSCs with BFP-4 enhanced osteoblastic differentiation and displayed greater bone-forming ability than BMP-7 treatment. These results suggest that BFP-4-stimulated cell therapy may be an efficient and cost-effective complement to BMP-7-based clinical therapy for bone regeneration and formation.

Update on the research and development of magnesium-based biodegradable implants and their clinical translation in orthopaedics.

ABSTRACTBiodegradable magnesium (Mg) or its alloys are desirable materials for development into new-generation internal fixation devices or implants with high biocompatibility, adequate mechanical modulus, and osteopromotive properties, which may overcome some of the drawbacks of the existing permanent orthopaedic implants with regard to stress-shielding of bone and beam-hardening effects on radiographic images. This review summarises the current research status of Mg-based orthopaedic implants in animals and clinical trials. First, detailed information of animal studies including bone fracture repair and anterior cruciate ligament reconstruction with the use of Mg-based orthopaedic devices is introduced. Second, the repair mechanisms of the Mg-based orthopaedic implants are also reviewed. Afterwards, reports of recent clinical cases treated using Mg-based implants in orthopaedics are summarised. Finally, the challenges and the strategies of the use of Mg-based orthopaedic implants are discussed. Taken together, the collected efforts in basic research, translational work, and clinical applications of Mg-based orthopaedic implants over the last decades greatly contribute to the development of a new generation of biodegradable metals used for the design of innovative implants for better treatment of orthopaedic conditions in patients with challenging skeletal disorders or injuries.

Electromagnetic stimulation increases mitochondrial function in osteogenic cells and promotes bone fracture repair

Bone fracture is a growing public health burden and there is a clinical need for non-invasive therapies to aid in the fracture healing process. Previous studies have demonstrated the utility of electromagnetic (EM) fields in promoting bone repair; however, its underlying mechanism of action is unclear. Interestingly, there is a growing body of literature describing positive effects of an EM field on mitochondria. In our own work, we have previously demonstrated that differentiation of osteoprogenitors into osteoblasts involves activation of mitochondrial oxidative phosphorylation (OxPhos). Therefore, it was reasonable to propose that EM field therapy exerts bone anabolic effects via stimulation of mitochondrial OxPhos. In this study, we show that application of a low intensity constant EM field source on osteogenic cells in vitro resulted in increased mitochondrial membrane potential and respiratory complex I activity and induced osteogenic differentiation. In the presence of mitochondrial inhibitor antimycin A, the osteoinductive effect was reversed, confirming that this effect was mediated via increased OxPhos activity. Using a mouse tibial bone fracture model in vivo, we show that application of a low intensity constant EM field source enhanced fracture repair via improved biomechanical properties and increased callus bone mineralization. Overall, this study provides supporting evidence that EM field therapy promotes bone fracture repair through mitochondrial OxPhos activation.

Troxerutin Stimulates Osteoblast Differentiation of Mesenchymal Stem Cell and Facilitates Bone Fracture Healing.

Troxerutin (TRX), a semi-synthetic derivative of the natural bioflavonoid rutin, is a bioactive flavonoid widely abundant in various fruits and vegetables. Known as vitamin P4, TRX has been demonstrated to have several activities including anti-inflammation, anti-oxidants, vasoprotection, and immune support in various studies. Although rutin, the precursor of troxerutin, was reported to have a protective role against bone loss, the function of TRX in skeletal system remains unknown. In the present study, we found that TRX promoted osteogenic differentiation of human mesenchymal stem cells (MSCs) in a concentration-dependent manner by stimulating the alkaline phosphatase (ALP) activity, calcium nodule formation and osteogenic marker genes expression in vitro. The further investigation demonstrated that TRX stimulated the expression of the critical transcription factor β-catenin and several downstream target genes of Wnt signaling, thus activated Wnt/β-catenin signaling. Using a femur fracture rats model, TRX was found to stimulate new bone formation and accelerate the fracture healing in vivo. Collectively, our data demonstrated that TRX could promote osteogenesis in vitro and facilitate the fracture healing in vivo, indicating that TRX may be a promising therapeutic candidate for bone fracture repair.

​Efficacy of Multi-ion Doped Plasma Spray Nano-hydroxyapatite Coated Titanium Implants in Long Bone Fracture Repair in Dogs- Radiographical and Bone Markers Evaluation

Background: Fracture of long bones is a common orthopaedic condition noticed in dogs and its primary goal is to completely restore the function of the injured limb as early as possible. Osteo-conductivity of hydroxyapatite can be improved further by decreasing the particle size to nanometre range and incorporation of inorganic materials in hydroxyapatite can enhance osteoblast cell material interactions. Strontium, Zinc, Silver and Fluorine are known to play an important role in the bone formation and also affect bone material characteristics such as crystallinity, degradation behaviour and mechanical properties. When doped with plasma spray nanohydroxyapatite, these multi-ions cause no harm to the physical environment during the degradation process of hydroxyapatite as these are nontoxic and play significant role in bone metabolism, growth and nourishment. Bone markers have tremendous potential as a rapid and sensitive method for assessing the response of the skeleton to medical or surgical interventions providing valuable information regarding bone turn over in animals. Hence, the current study was undertaken to evaluate the potential of multi-ion doped nano-hydroxyapatite coated intramedullary titanium implants in long bone fracture repair in dogs compared to the conventional intramedullary titanium implants through radiographical studies and evaluation of bone markers. Methods: Radiographical evaluation, Sandwich ELISA kits developed by Bioassay technology laboratory. Result: Plasma spray nano-hydroxyapatite coated titanium intramedullary implants have shown excellent osteo-conductivity when doped with multi-ions of Strontium, Zinc, Silver and Fluorine facilitating rapid osteoblastic activity and rapid bone turnover at the fracture site and complete fracture healing by 3rd week post-operatively as evidenced by radiographic scores and a peak BALP (Canine Bone Alkaline Phosphatase) values and early limb usage. Bone reabsorption and bone tissue remodelling due to osteoclastic action at the fracture site was quicker when the multi-ion doped nano-hydroxyapatite coated titanium intramedullary implants were used which is evidenced by the radiographic scores and highest CTX (Canine C-telopeptide of Type 1 Collagen) values indicating completion of fracture healing and near completion of bone tissue remodelling by 9th post-operative week in long bone fracture repair in dogs.

Biodegradable Antimicrobial Agent/Analgesic/Bone Morphogenetic Protein-Loaded Nanofibrous Fixators for Bone Fracture Repair

PurposePostoperative infection and pain management are of great concern to orthopedic surgeons. Although there are several protocols available to deal with these aspects, they are fraught with complications, such as cartilage damage, cardiovascular and neurological intoxication, and systemic adverse responses. Therefore, it is necessary to develop safe and effective perioperative protocols. In the current study, antimicrobial agents/analgesics/growth factor-embedded biodegradable hybrid fixators (polycaprolactone fixator + poly[lactide-co-glycolide] sheath-core structured nanofibers) for bone fracture repair were designed.MethodsThe biodegradable hybrid fixators were fabricated using solution-extrusion three-dimensional printing and electrospinning. In vitro, the characteristics of the hybrid fixators were examined. Additionally, the release of the incorporated vancomycin, ceftazidime, lidocaine, and bone morphogenetic protein-2 (BMP-2) was evaluated. The in vivo efficacy including drug-eluting properties, fracture repair, and pain management of the biomolecule-loaded nanofibrous fixators was investigated in rabbit rib-fracture models.ResultsThe nanofibrous fixators released vancomycin, ceftazidime, and lidocaine in a sustained manner under both in vitro and in vivo conditions and protected BMP-2 from burst release. The implantation of these hybrid fixators around the fractured rib significantly improved animal activities and bone union, indicating that the inclusion of analgesic in the fixator effectively reduced postsurgical pain and thereby helped in recovery.ConclusionThe novel biomolecule-loaded nanofibrous hybrid fixators resulted in excellent therapeutic outcomes. These fixators may be effective in the repair of rib fractures in clinical settings and may help mitigate surgical complications, such as infection, nonunion, and intolerable postoperative pain.