Mesenchymal Stem Cells-Involved Strategies for Rheumatoid Arthritis Therapy.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the joints and bone destruction. Because of systemic administration and poor targeting, traditional anti-rheumatic drugs have unsatisfactory treatment efficacy and strong side effects, including myelosuppression, liver or kidney function damage, and malignant tumors. Consequently, mesenchymal stem cells (MSCs)-involved therapy is proposed for RA therapy as a benefit of their immunosuppressive and tissue-repairing effects. This review summarizes the progress of MSCs-involved RA therapy through suppressing inflammation and promoting tissue regeneration and predicts their potential clinical application.

Microvascular endothelial cells derived from spinal cord promote spinal cord injury repair.

Neural regeneration after spinal cord injury (SCI) closely relates to the microvascular endothelial cell (MEC)-mediated neurovascular unit formation. However, the effects of central nerve system-derived MECs on neovascularization and neurogenesis, and potential signaling involved therein, are unclear. Here, we established a primary spinal cord-derived MECs (SCMECs) isolation with high cell yield and purity to describe the differences with brain-derived MECs (BMECs) and their therapeutic effects on SCI. Transcriptomics and proteomics revealed differentially expressed genes and proteins in SCMECs were involved in angiogenesis, immunity, metabolism, and cell adhesion molecular signaling was the only signaling pathway enriched of top 10 in differentially expressed genes and proteins KEGG analysis. SCMECs and BMECs could be induced angiogenesis by different stiffness stimulation of PEG hydrogels with elastic modulus 50-1650 Pa for SCMECs and 50-300 Pa for BMECs, respectively. Moreover, SCMECs and BMECs promoted spinal cord or brain-derived NSC (SNSC/BNSC) proliferation, migration, and differentiation at different levels. At certain dose, SCMECs in combination with the NeuroRegen scaffold, showed higher effectiveness in the promotion of vascular reconstruction. The potential underlying mechanism of this phenomenon may through VEGF/AKT/eNOS- signaling pathway, and consequently accelerated neuronal regeneration and functional recovery of SCI rats compared to BMECs. Our findings suggested a promising role of SCMECs in restoring vascularization and neural regeneration.

Multifunctional hydrogel modulates the immune microenvironment to improve allogeneic spinal cord tissue survival for complete spinal cord injury repair.

Transplantation of allogeneic adult spinal cord tissues (aSCTs) to replace the injured spinal cord, serves as a promising strategy in complete spinal cord injury (SCI) repair. However, in addition to allograft immune rejection, damage-associated molecular pattern (DAMP)-mediated inflammatory microenvironments greatly impair the survival and function of transplants. In this study, we aimed to regulate the immune microenvironment after aSCT implantation by developing a functional hybrid gelatin and hyaluronic acid hydrogel (F-G/H) modified with cationic polymers and anti-inflammatory cytokines that can gelatinize at both ends of the aSCT to glue the grafts for perfect matching at defects. The F-G/H hydrogel exhibited the capacities of DAMP scavenging, sustainably released anti-inflammatory cytokines, and reduced lymphocyte accumulation, thereby modulating the immune response and enhancing the survival and function of aSCTs. When the hydrogel was used in combination with a systemic immunosuppressive drug treatment, the locomotor functions of SCI rats were significantly improved after aSCTs and F-G/H transplantation. This biomaterial-based immunomodulatory strategy may provide the potential for spinal cord graft replacement for treating SCI. STATEMENT OF SIGNIFICANCE: In this study, we aimed to regulate the immune microenvironment by developing a functional hybrid gelatin and hyaluronic acid hydrogel (F-G/H) modified with cationic polymers and anti-inflammatory cytokines that can gelatinize at both ends of the aSCT to glue the grafts for perfect matching at defects. We found that with the treatment of F-G/H hydrogel, the aSCT survival and function was significantly improved, as a result of reducing recruitment and activation of immune cells through TLR- and ST-2- related signaling. With the combination of immunosuppressive drug treatment, the locomotor functions of SCI rats were significantly improved after aSCTs and F-G/H transplantation. Findings from this work suggest the potential application of the F-G/H as a biomaterial-based immunoregulatory strategy for improving the therapeutic efficiency of the transplanted spinal cord graft for spinal cord injury repair.

2-BFI Provides Neuroprotection Against Fluorosis by Stabilizing Endoplasmic Reticulum-Mitochondria Contact Sites and Inhibiting Activation of the NLRP3 Inflammasome.

2-(2-benzofu-ranyl)-2-imidazoline (2-BFI) is a drug that has attracted much attention in recent years. It has a therapeutic effect on brain diseases in animal models such as Alzheimer's disease and cerebral infarction. However, whether 2-BFI affords neuroprotection against the toxicity of fluoride, which can cross the blood-brain barrier and cause neurological dysfunction is not known. We investigated the cell viability and apoptosis of SH-SY5Y cells and primary cultures of cortical neurons exposed to fluoride, and 2-BFI was used to protect both two kinds of cells against the effects of fluoride. We found that 2-BFI can provide neuroprotection on SH-SY5Y cells and primary cultures of cortical neurons upon fluorosis by maintaining the stability of endoplasmic reticulum-mitochondria contact sites and inhibiting activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome. This study may provide a new method for protecting against the neurotoxicity induced by fluoride exposure.

Acidity-Triggered Transformable Polypeptide Self-Assembly to Initiate Tumor-Specific Biomineralization.

Biomineralization is a normal physiological process that includes nucleation, crystal growth, phase transformation, and orientation evolution. Notably, artificially induced biomineralization in the tumor tissue has emerged as an unconventional yet promising modality for malignancy therapy. However, the modest ion-chelating capabilities of carboxyl-containing biomineralization initiators lead to a deficient blockade, thus compromising antitumor efficacy. Herein, a biomineralization-inducing nanoparticle (BINP) is developed for blockade therapy of osteosarcoma. BINP is composed of dodecylamine-poly((γ-dodecyl-l-glutamate)-co-(l-histidine))-block-poly(l-glutamate-graft-alendronate) and combines a cytomembrane-insertion moiety, a tumor-microenvironment (TME)-responsive component, and an ion-chelating motif. After intravenous injection into osteosarcoma-bearing mice, BINP responds to the acidic TME to expose the dodecyl group on the surface of the expanded nanoparticles, facilitating their cytomembrane insertion. Subsequently, the protruding bisphosphonic acid group triggers continuous ion deposition to construct a mineralized barrier around the tumor, which blocks substance exchange between the tumor and surrounding normal tissues. The BINP-mediated blockade therapy displays tumor inhibition rates of 59.3% and 52.1% for subcutaneous and orthotopic osteosarcomas, respectively, compared with the Control group. In addition, the suppression of osteoclasts by the alendronate moiety alleviates bone dissolution and further inhibits pulmonary metastases. Hence, the BINP-initiated selective biomineralization provides a promising alternative for clinical osteosarcoma therapy.

Osteoimmunity-Regulating Biomimetically Hierarchical Scaffold for Augmented Bone Regeneration.

Engineering a proper immune response following biomaterial implantation is essential to bone tissue regeneration. Herein, a biomimetically hierarchical scaffold composed of deferoxamine@poly(ε-caprolactone) nanoparticles (DFO@PCL NPs), manganese carbonyl (MnCO) nanosheets, gelatin methacryloyl hydrogel, and a polylactide/hydroxyapatite (HA) matrix is fabricated to augment bone repair by facilitating the balance of the immune system and bone metabolism. First, a 3D printed stiff scaffold with a well-organized gradient structure mimics the cortical and cancellous bone tissues; meanwhile, an inside infusion of a soft hydrogel further endows the scaffold with characteristics of the extracellular matrix. A Fenton-like reaction between MnCO and endogenous hydrogen peroxide generated at the implant-tissue site triggers continuous release of carbon monoxide and Mn2+ , thus significantly lessening inflammatory response by upregulating the M2 phenotype of macrophages, which also secretes vascular endothelial growth factor to induce vascular formation. Through activating the hypoxia-inducible factor-1α pathway, Mn2+ and DFO@PCL NP further promote angiogenesis. Moreover, DFO inhibits osteoclast differentiation and synergistically collaborates with the osteoinductive activity of HA. Based on amounts of data in vitro and in vivo, strong immunomodulatory, intensive angiogenic, weak osteoclastogenic, and superior osteogenic abilities of such an osteoimmunity-regulating scaffold present a profound effect on improving bone regeneration, which puts forward a worthy base and positive enlightenment for large-scale bone defect repair.

Retraction Notice to: lncRNA CEBPA-AS1 Overexpression Inhibits Proliferation and Migration and Stimulates Apoptosis of OS Cells via Notch Signaling.

[This retracts the article DOI: 10.1016/j.omtn.2019.10.017.].

[Clinical observation on plastic splint treatment of middle clavicle fracture based on a new classification].

OBJECTIVE: According to 73 patients with middle clavicle fracture treated conservatively, a new classification of middle clavicle fracture was proposed, and the clinical effect of plastic splint in the treatment of middle clavicle fracture was observed. METHODS: Total 73 patients with middle clavicle fracture treated with plastic splint from September 2018 to August 2020 were analyzed retrospectively. All the patients were divided into 4 types according to the degree of fracture displacement. There were 16 cases of typeⅠ, including 7 males and 9 females, ranging in age from 18 to 37 years old, with a mean of (28.6±7.8) years old;12 cases of mild disease, 3 cases of moderate disease and 1 case of severe disease. There were 16 cases of type Ⅱ, including 6 males and 10 females, ranging in age from 25 to 49 years old, with a mean of (37.3±9.4) years old;5 cases of mild disease, 8 cases of moderate disease and 3 cases of severe disease. There were 7 cases of type Ⅲ, including 4 males and 3 females, ranging in age from 33 to 57 years old;2 cases of mild disease, 3 cases of moderate disease and 2 cases of severe disease. There were 34 cases of type Ⅳ, including 16 males and 18 females, ranging in age from 48 to 82 years old, with a mean of(66.4±14.9) years old;7 cases of mild disease, 17 cases of moderate disease and 10 cases of severe disease. All patients received plastic splint external fixation for 4 weeks. Visual analgue scale (VAS) and Constant-Murley shoulder scores before treatment and 1, 3 and 9 months after treatment were observed and recorded to evaluate the change of pain degree and shoulder function recovery before and after treatment. The patients' satisfaction with the appearance after treatment was recorded at the latest follow-up. The X-ray findings at the latest follow-up were used to judge whether the patient had fracture nonunion. And according to the fracture healing time and imaging findings, the excellent and good rate of clinical curative effect in patients with different types was obtained. RESULTS: All patients were followed up, and the duration ranged from 9 to 11 months, with a mean of (9.8±0.7) months. The VAS scores of typeⅠ, typeⅡand type Ⅳ before treatment were 2.88±0.83, 3.67±0.80 and 6.92±1.71 respectively, which were decreased to 0.54±0.19, 0.77±0.25 and 1.18±0.17 respectively after 9 months of treatment. The Constant-Murley shoulder scores of typeⅠ, typeⅡand type Ⅳ were 65.81±2.09, 63.50±2.22 and 47.93±2.91 respectively before treatment, and increased to 88.56±2.11, 85.12±2.23 and 71.25±2.16 respectively after 9 months of treatment. Five patients were not satisfied with the appearance after treatment;6 patients had no obvious continuous callus passing through after 9 months of treatment, which was fracture nonunion. CONCLUSION: The classification of middle clavicle fracture is more appropriate to the clinic, which has a certain clinical guiding significance for the selection of treatment methods and prognosis of middle clavicle fracture. Plastic splint is effective in the treatment of middle clavicle fracture without obvious displacement and overlapping displacement, and the incidence of complications is low. It can be popularized in clinic.

The effects of cages implantation on surgical and adjacent segmental intervertebral foramina.

OBJECTION: The overarching goal of our research was to compare the clinical and radiological outcomes with different sizes of cages implantation in anterior cervical discectomy and fusion (ACDF), and to evaluate the effects on surgical and adjacent segmental intervertebral foramina. METHODS: The clinical data of 61 patients were analyzed retrospectively. The radiological data included the surgical intervertebral disk space height before (H0) and after surgery (H), the preoperative mean height of adjacent segments (Hm), the area and height of the surgical and adjacent segment foramen, the surgical segmental Cobb angle (α1), and C2-7Cobb angle (α2). The calculation of clinical data was conducted by Japanese Orthopaedic Association Scores (JOA), the recovery rate of JOA scores and visual analog scales (VAS). In accordance with the different ranges of distraction (H/Hm), patients were classified into three groups: group A (H/Hm<1.20, n=13), group B (1.20≤H/Hm≤1.80, n=37), and group C (H/Hm>1.80, n=11). RESULTS: After the operation and at the final follow-up, our data has demonstrated that the area and height of surgical segmental foramen all increased by comparing those of preoperation in three groups (all P<0.05). However, except for a decrease in group C (all P<0.05), the adjacent segmental foramina showed no significant changes (all P>0.05). The area and height of the surgical segment foramen and the distraction degree were positively correlated (0

Down-Regulation of microRNA-30d Alleviates Intervertebral Disc Degeneration Through the Promotion of FOXO3 and Suppression of CXCL10.

MicroRNAs (miRNAs/miRs) are important biomarkers for the progression of intervertebral disc degeneration (IDD). We investigated the role of miR-30d in IDD progression through its interactions with forkhead box O3 (FOXO3) and C-X-C motif ligand 10 (CXCL10). We first measured the expression of miR-30d, FOXO3, and CXCL10 in NP cells cultured from IDD patients. RNA-immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were then employed to test the relationship among miR-30d, FOXO3, and CXCL10. Besides, gain- and loss-of function approaches were performed to assess the functional roles of miR-30d and FOXO3 in IDD in vitro and in vivo. We found high expression of miR-30d and CXCL10 and low expression of FOXO3 in IDD. We showed that miR-30d specifically targeted FOXO3, and that down-regulation of miR-30d promoted proliferation and inhibited apoptosis of NP cells in IDD by increasing the expression of FOXO3. Besides, FOXO3 inhibited apoptosis of NP cells by downregulation of CXCL10 expression. Moreover, inhibition of miR-30d promoted proliferation and inhibited apoptosis of NP cells in IDD by decreasing CXCL10. Furthermore, findings in the mouse IDD model confirmed the inhibitory role of decreased miR-30d in IDD progression. Thus, we show that downregulation of miR-30d could promote the proliferation of NP cells by increasing FOXO3 and decreasing CXCL10 expression, which may provide a novel therapeutic target for IDD.

Thermogel Delivers Oxaliplatin and Alendronate in situ for Synergistic Osteosarcoma Therapy.

The therapeutic effect of osteosarcoma (OS) has not made extraordinary progress in the past few decades. Oxaliplatin (OXA) is a widely used clinical anti-tumor drug. Recent studies have shown that OXA can trigger anti-tumor immunity by inducing immunogenic death (ICD). Alendronate (ALN) has been used to threaten the skeletal system tumors because of the unique bone affinity and the ability to inhibit bone destruction. In this study, we co-loaded OXA and ALN on mPEG45-PLV19 thermo-sensitive hydrogel to perform in situ treatment on the mouse OS model. Slowly released OXA can induce immunogenic death of tumor cells. At the same time, thermo-sensitive hydrogels can induce the accumulation of cytotoxic T lymphocytes. Besides, ALN could synergistically diminish tumors and prevent bone destruction. This system could synergistically inhibit the progression of OS and lung metastasis and has no toxicity to various organs throughout the body.

Construction of an integrated human osteosarcoma database, HOsDb, based on literature mining, microarray analysis, and database retrieval.

BACKGROUND: Osteosarcoma (OS) is the most frequent primary malignancy of bone with a high incidence in adolescence. This study aimed to construct a publicly available, integrated database of human OS, named HOsDb. METHODS: Microarray data, current databases, and a literature search of PubMed were used to extract information relevant to human OS-related genes and their transcription factors (TFs) and single nucleotide polymorphisms (SNPs), as well as methylation sites and microRNAs (miRNAs). This information was collated for constructing the HOsDb. RESULTS: In total, we identified 7191 OS tumor-related genes, 763 OS metastasis-related genes, and 1589 OS drug-related genes, corresponding to 190,362, 21,131, and 41,135 gene-TF pairs, respectively, 3,749,490, 358,361, and 767,674 gene-miRNA pairs, respectively; and 28,386, 2532, and 3943 SNPs, respectively. Additionally, 240 OS-related miRNAs, 1695 genes with copy number variations in OS, and 18 genes with methylation sites in OS were identified. These data were collated to construct the HOsDb, which is available at www.hosdatabase.com. Users can search OS-related molecules using this database. CONCLUSION: The HOsDb provides a platform that is comprehensive, quick, and easily accessible, and it will enrich our current knowledge of OS.

lncRNA CEBPA-AS1 Overexpression Inhibits Proliferation and Migration and Stimulates Apoptosis of OS Cells via Notch Signaling.

Osteosarcoma (OS) is the most common primary bone malignancy derived from primitive bone-forming mesenchymal cells. Long noncoding RNA (lncRNA) expression profiles have been intensively studied for their involvement in OS. Herein, we clarify whether lncRNA CEBPA-AS1 is a regulator of NCOR2 in OS cells. Microarray-based expression analysis identified OS-related differentially expressed lncRNA and predicted microRNAs (miRs) binding to lncRNA and mRNA. lncRNA CEBPA-AS1 and NCOR2 were found to be weakly expressed in OS tissues and cells. Next, functional investigation revealed that lncRNAs CEBPA-AS1 bound to miR-10b-5p to upregulate NCOR2. Following that, gene-targeted knockdown and overexpressed recombinant vectors of lncRNA CEBPA-AS1 and NCOR2 were constructed to explore the effects of lncRNA CEBPA-AS1 and NCOR2 on cell proliferation, differentiation, migration, and apoptosis. Finally, tumor formation was measured in nude mice. lncRNA CEBPA-AS1 overexpression or NCOR2 elevation inhibited cell proliferation and migration, and alkaline phosphatase (ALP) and bone gla protein (BGP) activity, while enhancing apoptosis and tumor formation. Furthermore, NCOR2 was elevated in response to lncRNA CEBPA-AS1 overexpression, thus repressing the Notch signaling pathway. Taken together, lncRNA CEBPA-AS1 overexpression inhibits OS progression through diminishing activation of the Notch signaling pathway via upregulating NCOR2. Therefore, lncRNA CEBPA-AS1 may serve as a molecular target for treating OS.

Down-regulation of RAC2 by small interfering RNA restrains the progression of osteosarcoma by suppressing the Wnt signaling pathway.

Osteosarcoma (OS) is the most common primary malignancy of bone and is characterized by a high malignant and metastatic potential. Microarray-based differentially expressed gene screening determined RAC2 as the candidate gene related to OS. Highly expressed RAC2 and activated Wnt signaling pathway were determined in OS tissues using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. The OS cells were transfected with siRNA-RAC2 or treated with BIO (activator of Wnt pathway), whereby the effects of siRNA-RAC2 on cell proliferation, invasion, cycle and apoptosis were analyzed by CCK-8, Transwell assay and flow cytometry. The mRNA and protein levels of RAC2 and the Wnt signaling pathway-, proliferation- and apoptosis-related genes in OS cells were determined by RT-qPCR and Western blot assay. Importantly, siRNA-mediated RAC2 silencing inhibited the activation of the Wnt signaling pathway in OS. siRNA-RAC2 inhibited the proliferation and invasion, while impeded OS cell cycle progression and facilitated cell apoptosis. However, activation of Wnt signaling pathway reversed the effects of siRNA-RAC2. Finally, orthotopic xenograft OS mouse model confirmed the in vivo anti-tumor effects by silencing RAC2. Taken together, RAC2 gene silencing could suppress OS progression. The mechanism was obtained by inhibiting the activation of the Wnt signaling pathway.

MicroRNA-200c promotes osteogenic differentiation of human bone mesenchymal stem cells through activating the AKT/ß-Catenin signaling pathway via downregulating Myd88.

During the human bone formation, the event of osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs) is vital, and recent evidence has emphasized the important role of microRNAs (miRNAs) in osteogenic differentiation of hBMSCs. This study aims to examine the potential effects of miR-200c in osteogenic differentiation of hBMSCs and understand their underlying mechanisms. HBMSCs were obtained via human bone marrow. During osteogenic induction and differentiation, cells were transfected with different plasmids with the intention of investigating the roles of miR-200c on osteogenic differentiation, calcium salt deposition, alkaline-phosphatase (ALP) activity, mineralized nodule formation, osteocalcin (OCN) content, and proliferation of osteoblasts. Following transfection, dual luciferase reporter gene assay was conducted so as to explore the correlation between miR-200c and Myd88. Moreover, the AKT/ß-Catenin signaling pathway was blocked with an AKT/ß-Catenin inhibitor, AKTi, to investigate its involvement. The hBMSCs were successfully isolated from human bone marrow. Myd88 was determined as a target gene of miR-200c. Gain and loss-of-function assays confirmed that overexpression of miR-200c, or silencing of Myd88 promoted osteogenic differentiation, increased calcium salt deposition, ALP activity, mineralized nodule formation, and enhanced the proliferation of osteoblasts following osteogenic differentiation of hBMSCs. Meanwhile, the downregulation of miR-200c has been shown to have the opposite effect. Furthermore, these findings showed that the miR-200c overexpression activated the AKT/ß-Catenin signaling pathway by targeting Myd88. To sum up, the miR-200c upregulation induces osteogenic differentiation of hBMSCs by activating the AKT/ß-Catenin signaling pathway via the inhibition of Myd88, providing a target for treatment of bone repair.

MicroRNA-377 exerts a potent suppressive role in osteosarcoma through the involvement of the histone acetyltransferase 1-mediated Wnt axis.

It has been demonstrated that microRNAs (miRNAs) may contribute to tumorigenesis and tumor growth in osteosarcoma (OS), which is a primary malignant tumor of bone frequently diagnosed in adolescents and young people. The purpose of our investigation was to evaluate the functional relevance of miR-377 in OS and to investigate whether the mechanism was related to the histone acetyltransferase 1 (HAT1)-mediated Wnt signaling pathway. By screening differentially expressed genes in microarray GSE47572, HAT1 was found to be a candidate gene of interest. Besides, the regulatory miRNA (miR-377) of HAT1 was also selected. The interaction among miR-377, HAT1, and the Wnt signaling pathway was evaluated. In addition, the miR-377 expression was altered in OS cells (U-2OS and SOSP-9607) to assess the in vitro cell apoptosis and the in vivo tumor growth. OS tissues presented elevated HAT1 expression and decreased miR-377 expression. A putative miR-377 binding site in HAT1 3'-UTR HAT1 was verified. Cells with miR-377 overexpression or HAT1 silencing were observed to exhibit reduced HAT1 expression and promoted apoptosis, accompanied by blockade of Wnt signaling. Moreover, the in vivo experiment revealed that miR-377 overexpression or HAT1 silencing inhibited tumor growth and reduced tumor size in nude mice. Taken together, our results conclude that miR-377 may promote OS cell apoptosis through inactivation of the HAT1-mediated Wnt signaling pathway, highlighting the potential therapeutic effect of miR-377 on OS treatment.

Electrospun Polylactide-Nano-HydroxyapatiteVancomycin Composite Scaffolds for Advanced Osteomyelitis Therapy.

The development of effective treatment for the infection and bone defect resulting from advanced osteomyelitis is an urgent task in the orthopedic clinic. To simultaneously address the issues of infection and bone defect, the multifunctional electrospun scaffolds composed of polylactide (PLA), nano-hydroxyapatite-graft-polylactide (nHA-g-PLA), and antibiotic vancomycin (VAN) were developed for the treatment of advanced osteomyelitis in the present study. The composite scaffolds PLA/nHA/VAN could sustainably release VAN and exhibited excellent antibacterial activity toward S. aureus. The rough surface of PLA/nHA/VAN induced by the presence of nHA-g-PLA promoted the adhesion and proliferation of osteoblasts. More interestingly, PLA/nHA/VAN, especially PLA/nHA10/VAN8, reduced bone infections and boosted bone regeneration at the defect site with better outcomes than other treatment groups. In conclusion, it has been demonstrated to be highly effective for the treatment of osteomyelitis using the scaffolds with sustained release properties, which has great potential for real application in the orthopedic clinic.

BMP-2-releasing gelatin microspheres/PLGA scaffolds for bone repairment of X-ray-radiated rabbit radius defects.

The purpose of this research is to assess the feasibility of poly(lactic-co-glycolic) acid (PLGA) incorporating gelatin microspheres (PLGA/GMs scaffold) for enhancing osteogenesis in vitro and at a radius defect of rabbits after X-ray radiation in vivo. After incorporating gelatin microspheres, PLGA scaffold demonstrated improved mechanical properties. Moreover, a sustained release property of recombinant human bone morphogenetic protein-2 (BMP-2) was achieved in BMP-2-releasing PLGA/GMs scaffold. BMP-2-releasing PLGA/GMs scaffold also enhanced proliferation and osteogenesis of rabbit bone mesenchymal stem cells (BMSCs) in vitro, indicating the bioactivity of BMP-2. After finishing X-ray radiation of the radius bone, 20-mm radius bone defects were generated, followed by being implanted with BMP-2-releasing PLGA/GMs scaffolds with or without bone marrow. Both PLGA/GMs scaffolds containing bone marrow or BMP-2 showed more obvious enhancement for bone regeneration than the empty scaffolds (control) at the radius defect. In the X-ray radiated groups, however, the bone regeneration was inhibited either with bone marrow or BMP-2. When combined with bone marrow, the BMP-2 showed significantly high osteogenic effect, regardless of X-ray radiation. It is considered that it is a promising way to repair bone defects even after X-ray radiation by a combination of bone marrow with the BMP-2-releasing PLGA/GMs scaffold.