Rat Bone Marrow Stromal Cells Research Articles

Skeletal Effects of a Prolonged Oral Metformin Treatment in Adult Wistar Rats.

We previously showed that a 3-week oral metformin (MET) treatment enhances the osteogenic potential of bone marrow stromal cells (BMSCs) and improves several bone histomorphometric parameters in Wistar rats with metabolic syndrome (MetS). However, the skeletal effects of extended periods of MET need to be completely elucidated. Hence, in this study, the impact of a prolonged (3-month) MET treatment was investigated on bone architecture, histomorphometric and biomechanics variables, and osteogenic potential of BMSCs in Wistar rats with or without MetS. Young male Wistar rats (n=36) were randomized into four groups (n=9) that received either 20% fructose (F), MET (MET), F plus MET treatments (FMET), or drinking water alone (Veh). Rats were euthanized, blood was collected, and bones were dissected and processed for peripheral quantitative computed tomography (pQCT) analysis, static and dynamic histomorphometry, and bone biomechanics. In addition, BMSCs were isolated to determine their osteogenic potential. MET affected trabecular and cortical bone, altering bone architecture and biomechanics. Furthermore, MET increased the pro-resorptive profile of BMSCs. In addition, fructose-induced MetS practically did not affect the the structural or mechanical variables of the skeleton. A 3-month treatment with MET (with or without MetS) affects bone architecture and biomechanical variables in Wistar rats.

Exploring miR-21 as a key regulator in two distinct approaches of bone marrow stromal cells differentiation into Schwann-like cells.

The differentiation of bone marrow stromal cells (BMSCs) into Schwann-like cells (SCLCs) has the potential to promote the structural and functional restoration of injured axons. However, the optimal induction protocol and its underlying mechanisms remain unclear. This study aimed to compare the effectiveness of different induction protocols in promoting the differentiation of rat BMSCs into SCLCs and to explore their potential mechanisms. BMSCs were induced using two distinct methods: a composite factor induction approach (Protocol-1) and a conditioned culture medium induction approach (Protocol-2). The expression of Schwann cells (SCs) marker proteins and neurotrophic factors (NTFs) in the differentiated cells was assessed. Cell proliferation and apoptosis were also measured. During induction, changes in miR-21 and Sprouty RTK signaling antagonist 2 (SPRY2) mRNA were analyzed. Following the transfection of BMSCs with miR-21 agomir or miR-21 antagomir, induction was carried out using both protocols, and the expression of SPRY2, ERK1/2, and SCs marker proteins was examined. The results revealed that NTFs expression was higher in Protocol-1, whereas SCs marker proteins expression did not significantly differ between the two groups. Compared to Protocol-1, Protocol-2 exhibited enhanced cell proliferation and fewer apoptotic and necrotic cells. Both protocols showed a negative correlation between miR-21 and SPRY2 expression throughout the induction stages. After induction, the miR-21 agomir group exhibited reduced SPRY2 expression, increased ERK1/2 expression, and significantly elevated expression of SCs marker proteins. This study demonstrates that Protocol-1 yields higher NTFs expression, whereas Protocol-2 results in stronger SCLCs proliferation. Upregulating miR-21 suppresses SPRY2 expression, activates the ERK1/2 signaling pathway, and promotes BMSC differentiation into SCLCs.

Local application of zoledronate inhibits early bone resorption and promotes bone formation.

Nonunion resulting from early bone resorption is common after bone transplantation surgery. In these patients, instability or osteoporosis causes hyperactive catabolism relative to anabolism, leading to graft resorption instead of fusion. Systemic zoledronate administration inhibits osteoclastogenesis and is widely used to prevent osteoporosis; however, evidence on local zoledronate application is controversial due to osteoblast cytotoxicity, uncontrolled dosing regimens, and local release methods. We investigated the effects of zolendronate on osteoclastogenesis and osteogenesis and explored the corresponding signaling pathways. In vitro cytotoxicity and differentiation of MC3T3E1 cells, rat bone marrow stromal cells (BMSCs) and preosteoclasts (RAW264.7 cells) were evaluated with different zolendronate concentrations. In vivo bone regeneration ability was tested by transplanting different concentrations of zolendronate with β-tricalcium phosphate (TCP) bone substitute into rat femoral critical-sized bone defects. In vitro, zolendronate concentrations below 2.5 × 10-7M did not compromise viability in the three cell lines and did not promote osteogenic differentiation in MC3T3E1 cells and BMSCs. In RAW264.7 cells, zoledronate inhibited extracellular regulated protein kinases and c-Jun n-terminal kinase signaling, downregulating c-Fos and NFATc1 expression, with reduced expression of fusion-related dendritic cell‑specific transmembrane protein and osteoclast-specific Ctsk and tartrate-resistant acid phosphatase (. In vivo, histological staining revealed increased osteoid formation and neovascularization and reduced fibrotic tissue with 500μM and 2000μM zolendronate. More osteoclasts were found in the normal saline group after 6weeks, and sequential osteoclast formation occurred after zoledronate treatment, indicating inhibition of bone resorption during early callus formation without inhibition of late-stage bone remodeling. In vivo, soaking β-TCP artificial bone with 500μM or 2000μM zoledronate is a promising approach for bone regeneration, with potential applications in bone transplantation.

Stiffness and BMP-2 Mimetic Peptide Jointly Regulate the Osteogenic Differentiation of Rat Bone Marrow Stromal Cells in a Gelatin Cryogel.

Both biochemical and mechanical cues could regulate the function of stem cells, but the interaction mechanism of their signaling pathway remains unclear, especially in the three-dimensional (3D) culture mode. Higher matrix stiffness promotes osteogenic differentiation of stem cells, and bone morphogenic protein-2 (BMP-2) has been clinically applied to promote bone regeneration. Here, the crosstalk of extracellular mechanical signals on BMP-2 signaling was investigated in rat bone marrow stromal cells (rMSCs) cultured inside cryogels with interconnective pores. Stiff cryogel independently promoted osteogenic differentiation and enhanced the autocrine secretion of BMP-2, thus stimulating increased phosphorylation levels of the Smad1/5/8 complex. BMP-2 mimetic peptide (BMMP) and high cryogel stiffness jointly guided the osteogenic differentiation of rMSCs. Inhibition of rho-associated kinase (ROCK) by Y-27632 or inhibition of nonmuscle myosin II (NM II) by blebbistatin showed that osteogenesis induction by BMP-2 signaling, as well as autocrine secretion of BMP-2 and phosphorylation of the Smad complex, requires the involvement of cytoskeletal tension and ROCK pathway signaling. An interconnective microporous cryogel scaffold promoted rMSC osteogenic differentiation by combining matrix stiffness and BMMP, and it accelerated critical cranial defect repair in the rat model.

Digital light processing of customized elastic scaffolds by efficient thiol-yne crosslinking

Digital light processing (DLP) based 3D printing technology has the advantages of fast printing rate and high spatial resolution in the manufacture of tissue engineering scaffolds. However, the limited availability of printable materials for DLP technology, especially the lack of biodegradable elastomeric materials hinders the development of customized soft tissue scaffolds. Herein, liquid poly(4-methyl-ε-caprolactone) dialkynylate (PMCLDY) was prepared as a DLP printable ink based on efficient thiol-yne photocrosslinking. With the aid of photorheology and in situ FT-IR and tensile tests, an ink formulation for DLP printing was optimized as the P50 ink (PMCLDY to diluent PEGDY mass ratio of 1), which possessed fast cure rates (<15 s), low viscosity (<2 Pa·s), moderate mechanical properties (failure strain > 40 %) and maximum toughness (0.153 MJ·m−3). A commercial DLP printer equipped with the P50 ink realized 3D scaffolds models with microstructure and macroscopic shape precisely. It was demonstrated that the 3D printed scaffold with biodegradability could withstand dynamic compression cycles. Furthermore, the cytocompatibility experiments showed that the scaffold could effectively support the growth and proliferation of rat bone marrow stromal cells (BMSCs). These results demonstrate that the P50 ink is a promising material for manufacturing elastic scaffolds by DLP printing for tissue engineering applications.

Graphene Oxide Functionalized Gelatin Methacryloyl Microgel for Enhanced Biomimetic Mineralization and in situ Bone Repair.

The formation of bone-like apatite (Ap) on natural polymers through biomimetic mineralization using simulated body fluid (SBF) can improve osteoconductivity and biocompatibility, while lowering immunological rejection. Nonetheless, the coating efficiency of the bone-like Ap layer on natural polymers requires improvement. Carbonyls (-COOH) and hydroxyls (-OH) are abundant in graphene oxide (GO), which may offer more active sites for biomimetic mineralization and promote the proliferation of rat bone marrow stromal cells (BMSCs). In this study, gelatin methacryloyl (GelMA) microgels were infused with GO (0, 0.5, 1, and 2 mg/mL) and embedded into microgels in SBF for 1, 7, and 14 days. Systematic in vitro and in vivo experiments were performed to evaluate the structure of the microgel and its effect on cell proliferation and ability to repair bone defects in rats. The resulting GO-GelMA-Ap microgels displayed a porous, interconnected structure with uniformly coated surfaces in bone-like Ap, and the Ca/P ratio of the 1 mg/mL GO-GelMA-Ap group was comparable to that of natural bone tissue. Moreover, the 1 mg/mL GO-GelMA-Ap group exhibited a greater Ap abundance, enhanced proliferation of BMSCs in vitro and increased bone formation in vivo compared to the GelMA-Ap group. Overall, this study offers a novel method for incorporating GO into microgels for bone tissue engineering to promote biomimetic mineralization.

Treatment of critical bone defects using calcium phosphate cement and mesoporous bioactive glass providing spatiotemporal drug delivery

Calcium phosphate cements (CPC) are currently widely used bone replacement materials with excellent bioactivity, but have considerable disadvantages like slow degradation. For critical-sized defects, however, an improved degradation is essential to match the tissue regeneration, especially in younger patients who are still growing. We demonstrate that a combination of CPC with mesoporous bioactive glass (MBG) particles led to an enhanced degradation in vitro and in a critical alveolar cleft defect in rats. Additionally, to support new bone formation the MBG was functionalized with hypoxia conditioned medium (HCM) derived from rat bone marrow stromal cells. HCM-functionalized scaffolds showed an improved cell proliferation and the highest formation of new bone volume. This highly flexible material system together with the drug delivery capacity is adaptable to patient specific needs and has great potential for clinical translation.

Highly resilient and fatigue-resistant poly(4-methyl-ε-caprolactone) porous scaffold fabricated via thiol-yne photo-crosslinking/salt-templating for soft tissue regeneration

Elastomeric scaffolds, individually customized to mimic the structural and mechanical properties of natural tissues have been used for tissue regeneration. In this regard, polyester elastic scaffolds with tunable mechanical properties and exceptional biological properties have been reported to provide mechanical support and structural integrity for tissue repair. Herein, poly(4-methyl-ε-caprolactone) (PMCL) was first double-terminated by alkynylation (PMCL-DY) as a liquid precursor at room temperature. Subsequently, three-dimensional porous scaffolds with custom shapes were fabricated from PMCL-DY via thiol-yne photocrosslinking using a practical salt template method. By manipulating the Mn of the precursor, the modulus of compression of the scaffold was easily adjusted. As evidenced by the complete recovery from 90% compression, the rapid recovery rate of >500 mm min−1, the extremely low energy loss coefficient of <0.1, and the superior fatigue resistance, the PMCL20-DY porous scaffold was confirmed to harbor excellent elastic properties. In addition, the high resilience of the scaffold was confirmed to endow it with a minimally invasive application potential. In vitro testing revealed that the 3D porous scaffold was biocompatible with rat bone marrow stromal cells (BMSCs), inducing BMSCs to differentiate into chondrogenic cells. In addition, the elastic porous scaffold demonstrated good regenerative efficiency in a 12-week rabbit cartilage defect model. Thus, the novel polyester scaffold with adaptable mechanical properties may have extensive applications in soft tissue regeneration.

YAP/TEAD1 and β-catenin/LEF1 synergistically induce estrogen receptor α to promote osteogenic differentiation of bone marrow stromal cells.

Bone remodeling is vital to the maintenance of bone homeostasis and may lead to destructive skeletal diseases once the balance is disrupted. Crosstalk between Wnt and estrogen receptor (ER) signaling has been proposed in bone remodeling, but the underlying mechanism remains unclear. This study was designed to explore the effect of Wnt-ER signaling during the osteogenic differentiation of bone marrow stromal cells (BMSCs). Rat BMSCs were isolated and identified using flow cytometry and stimulated with Wnt3a. Wnt3a treatment promoted osteogenic differentiation and mineralization of the BMSCs. Meanwhile, Wnt3a enhanced the expression of ERα as well as the canonical Wnt signaling mediator β-catenin and the alternative Wnt signaling effector Yes-associated protein 1 (YAP1). Interestingly, DNA pulldown assay revealed direct binding of transcriptional enhanced associate domain 1 (TEAD1) and lymphoid enhancer binding factor 1 (LEF1), transcriptional partners of YAP1 and β-catenin, respectively, to the promoter region of ERα. In addition, inhibition of TEAD1 and LEF1 suppressed Wnt3-promoted BMSC osteogenic differentiation and blocked Wnt3a-induced ERα expression. Furthermore, an in vivo model of femoral bone defect also supported that Wnt3a facilitated bone healing in an ERα-dependent way. Together, we suggest that Wnt3a promotes the osteogenic activity of BMSCs through YAP1 and β-catenin-dependent activation of ERα, via direct binding of TEAD1 and LEF1 to the ERα promoter.

Osteogenic differentiation of bone marrow stromal stem cells on a novel β titanium alloy-based micro-nano composite

The incorporation of nanoparticles into metallic biomaterials has been recognized as a significant approach to improve their bioactivity for biomedical applications. In this study, friction stir processing (FSP) was employed to incorporate TiO2 nanoparticles as bioactive reinforcement into the β titanium alloy Ti–35Nb–2Ta–3Zr (TNTZ) matrix to construct an integrated micro-nano composite layer. The effect of different TiO2 contents on the osteogenic capacity of rat bone marrow stromal stem cells (BMSCs) was studied. The TiO2/TNTZ composite layer exhibited a refined grain structure with a mean grain size of approximately 10 μm and a characteristic surface morphology of pronounced peaks and valleys with enhanced RSkw and RKur values. Moreover, TiO2/TNTZ significantly promoted the adhesion, proliferation, and spreading of BMSCs, upregulated the expression of genes related to osteogenesis (ALP and Runx2) up to nearly 1.5 times, and enhanced the expression of ALP and OCN (P < 0.05). The novel FSPed TiO2/TNTZ micro-nano composite possesses excellent surface characteristics and favorable biological activities, manifesting vast potential for upcoming clinical applications.

MiR-218-5p-dependent SOCS3 downregulation increases osteoblast differentiation inpostmenopausal osteoporosis

BackgroundPostmenopausal osteoporosis (POP) is a prevalent skeletal disease among elderly women. Previous study indicated that suppressor of cytokine signaling 3 (SOCS3) participates in the regulation of bone marrow stromal cell (BMSC) osteogenesis. Here, we further investigated the exact function and mechanism of SOCS3 in POP progression.MethodsBMSCs were isolated from Sprague–Dawley rats and treated with Dexamethasone (Dex). Alizarin Red staining and ALP activity assays were applied to assess the osteogenic differentiation of rat BMSCs under the indicated conditions. Osteogenic genes (ALP, OPN, OCN, COL1) mRNA levels were determined using quantitative RT-PCR. Luciferase reporter assay verified the interaction between SOCS3 and miR-218-5p. Rat models of POP were established in ovariectomized (OVX) rats to detect the in vivo effects of SOCS3 and miR-218-5p.ResultsWe found that silencing SOCS3 antagonized the suppressive effects of Dex on the osteogenic differentiation of BMSCs. SOCS3 was found to be targeted by miR-218-5p in BMSCs. The SOCS3 levels were negatively modulated by miR-218-5p in femurs of POP rats. MiR-218-5p upregulation promoted the BMSC osteogenic differentiation, while SOCS3 overexpression reversed the effects of miR-218-5p. Moreover, SOCS3 was highly expressed and miR-218-5p was downregulated in the OVX rat models, and silencing SOCS3 or overexpressing miR-218-5p alleviated POP in OVX rats by promoting osteogenesis.ConclusionSOCS3 downregulation mediated by miR-218-5p increases osteoblast differentiation to alleviate POP.

Mir-184 Regulates Bone Marrow Stromal Cells in Osteoporosis Rats via Targeting Special AT-Rich Sequence-Binding Protein 2 (Satb2)

Bone marrow stromal cells (BMSCs) participates in osteoporosis (OP) development and their differentiation can affect OP progression. miR-184 is involved in several diseases. However, miR-184’s role in BMSCs in osteoporosis is unclear. Rat BMSCs were isolated and assigned into control group, Mir-184 inhibitor group and Mir-184 group followed by analysis of Mir-184, Runx2 and OCN expression by Real time PCR, ALP activity and calcified nodules formation by Alizarin red staining. SD rats were separated into sham operation group, OP group and Mir-184 inhibitor group and bone density was assessed by micro-CT. Mir-184 inhibitor transfection significantly down-regulated Mir-184, increased expression of Runx2, OCN and Stab2 and promoted ALP activity (P&lt;0.05), which were all reversed by Mir-184 mimic. Satb2 was targeted by Mir-184. Transfection of Mir-184 inhibitor and shSATB2 lentivirus decreased Runx2 and OCN expression and reduced calcified nodules formation. Mir-184 down-regulation in OP rats promoted Runx2 and OCN expression and increased bone density. In conclusion, Mir-184 expression is increased in OP rat BMSCs and its down-regulation can target Satb2, which promote osteogenic differentiation and increase calcified nodule formation and ameliorate OP disease.

Surface modification of new innocuous Ti-Mo-Zr based alloys for biomedical applications.

To address the clinical challenges of modulus mismatch, lack of initial osteointegration and contain toxic elements towards traditional titanium and its alloys with surrounding bone tissue, a new β-type titanium alloy (Ti-12Mo-10Zr) designed by our group will be chosen as dental implant in this proposal due to its excellent properties, e.g. low young's modulus (~ 50.8 GPa) and excellent compressive yield strength (~ 430.89MPa). A modified hydrothermal and pressure method will be deployed to create tailored micro/nano topography and chemistry (phosphorus) on implant surface with the aim of promoting osteointegration. The formation process and mechanism of micro/nano-scaled hierarchical hybrid coating containing phosphorous will be revealed from the perspective of energetics and crystallography to realize co-design of multiple structure and chemical on Ti-12Mo-10Zr surface. The in vitro cytological performance of this hierarchical hybrid coating containing phosphorous will also be evaluated by co-culturing with rat bone marrow stromal cells This proposal will not only provide guidance and experimental database for next generation potential implant named Ti-12Mo-10Zr, but also display new insights to improve long-lasting stability for dental implant which demonstrate tremendous scientific significance.

Mussel-Inspired Organic–Inorganic Implant Coating Based on a Layer-by-Layer Method for Anti-infection and Osteogenesis

Lack of antibacterial properties and poor bioactivity of implants’ surfaces will increase the risk of implant-associated infections and poor osseointegration, subsequently leading to implant failure. In the present study, an organic–inorganic coating with anti-infection and osteogenesis properties was constructed on the titanium (Ti) implants to enhance the osseointegration. Inspired by the mussel, tannic acid (TA) with abundant catechol groups was chosen as a bonding medium to combine inorganic hydroxyapatite nanoparticles (nHA) with organic polyethylene glycol (PEG) via Layer-by-Layer (LbL) assembly methods. The prepared organic–inorganic coating on the implant (Ti-HP) could effectively prevent the adherence of protein and bacteria including S. aureus and E. coli through highly hydrophilic PEG, and the nHA ingredient endowed the coating with sufficient osteogenic ability to accelerate osteoblast differentiation of rat bone marrow stromal cells (BMSCs). Furthermore, the new bone formation around Ti-HP in vivo was significantly promoted compared with the pure Ti. The study provides a convenient and flexible way based on a polyphenol-assisted LbL method to form an organic–inorganic implant coating with multiple functions, demonstrating its potential for clinical applications in surface engineering of bone repair.

Gamma-Irradiated Bacterial Cellulose as a Three-Dimensional Scaffold for Osteogenic Differentiation of Rat Bone Marrow Stromal Cells

The effect of gamma-irradiation on bacterial cellulose (BC) was investigated in terms of improving its properties as scaffolds for tissue engineering. BC pellicles were exposed to 25, 50, and 75 kGy gamma-ray irradiation, and X-ray diffraction analyses showed that the crystallinity of the BC decreased as stronger irradiation accelerated BC’s degradation. Fourier transform infrared spectroscopy of the irradiated BC revealed the appearance of a new peak at 1724 cm–1, indicating the formation of a new carbonyl group due to the cleavage of glycosidic linkages of the BC. Rat bone marrow stromal cells seeded on the gamma-irradiated BC incubated in an osteogenic medium for 14 days produced calcium, a late marker for osteogenic differentiation, as shown by Alizarin Red S (ARS) staining. Gamma-irradiated BC with higher irradiation doses showed intense ARS staining indicating higher calcium deposition. These findings demonstrate the feasibility of using gamma-irradiated BC as a cytocompatible 3D scaffold for bone tissue regeneration.

S-allylmercapto-N-acetylcysteine protects bone cells from oxidation and improves femur microarchitecture in healthy and diabetic mice.

Oxidative stress is involved in the deterioration of bone quality and mechanical strength in both diabetic and aging adults. Therefore, we studied the ability of the antioxidant compound, S-allylmercapto-N-acetylcysteine (ASSNAC) to protect bone marrow stromal cells (BMSCs) from advanced glycation end-products (AGEs) cytotoxicity and improve bone microarchitecture of adult healthy and obese/diabetic (db/db) female mice. ASSNAC effect on AGEs-treated cultured rat BMSCs was evaluated by Neutral Red and XTT cell survival and reactive oxygen species (ROS) level assays. Its effect on healthy (C57BL/6) and obese/diabetic (C57BLKS/J Leprdb+/+; db/db) female mice femur parameters, such as (1) number of adherent BMSCs, (2) percentage of CD73+/CD45- cells in bone marrow (BM), (3) glutathione level in BM cells, and (4) femur microarchitecture parameters by microcomputed tomography, was studied. ASSNAC treatment protected BMSCs by significantly decreasing AGEs-induced ROS production and increasing their cellular resistance to the cytotoxic effect of AGEs. ASSNAC treatment of healthy female mice (50 mg/kg/day; i.p.; age 12-20 weeks) significantly increased the number of BMSCs (+60%), CD73+/CD45- cells (+134%), and glutathione level (+110%) in the femur bone marrow. Furthermore, it increased the femur length (+3%), cortical diameter (+3%), and cortical areal moment of inertia (Ct.MOI; +10%) a surrogate for biomechanical strength. In db/db mice that demonstrated a compromised trabecular bone and growth plate microarchitecture, ASSNAC treatment restored the trabecular number (Tb.N, +29%), bone volume fraction (Tb.BV/TV, +130%), and growth plate primary spongiosa volumetric bone mineral density (PS-vBMD, +7%) and thickness (PS-Th, +18%). In conclusion, this study demonstrates that ASSNAC protects bone marrow cells from oxidative stress and may improve bone microarchitecture in adult healthy and diabetic female mice.

Degradation-Kinetics-Controllable and Tissue-Regeneration-Matchable Photocross-linked Alginate Hydrogels for Bone Repair.

Photocross-linked alginate hydrogels, due to their biodegradability, biocompatibility, strong control for gelling kinetics in space and time, and admirable adaptability for in situ polymerization with a minimally invasive approach in surgical procedures, have created great expectations in bone regeneration. However, hydrogels with suitable degradation kinetics that can match the tissue regeneration process have not been designed, which limits their further application in bone tissue engineering. Herein, we finely developed an oxidation strategy for alginate to obtain hydrogels with more suitable degradation rates and comprehensively explored their physical and biological performances in vitro and in vivo to further advance the clinical application for the hydrogels in bone repair. The physical properties of the gels can be tuned via tailoring the degree of alginate oxidation. In particular, in vivo degradation studies showed that the degradation rates of the gels were significantly increased by oxidizing alginate. The activity, proliferation, initial adhesion, and osteogenic differentiation of rat and rabbit bone marrow stromal cells (BMSCs) cultured with/in the hydrogels were explored, and the results demonstrated that the gels possessed excellent biocompatibility and that the encapsulated BMSCs were capable of osteogenic differentiation. Furthermore, in vivo implantation of rabbit BMSC-loaded gels into tibial plateau defects of rabbits demonstrated the feasibility of hydrogels with appropriate degradation rates for bone repair. This study indicated that hydrogels with increasingly controllable and matchable degradation kinetics and satisfactory bioproperties demonstrate great clinical potential in bone tissue engineering and regenerative medicine and could also provide references for drug/growth-factor delivery therapeutic strategies for diseases requiring specific drug/growth-factor durations of action.

Stereocomplexation Reinforced High Strength Poly(L-lactide)/Nanohydroxyapatite Composites for Potential Bone Repair Applications.

Composite materials composed of polylactide (PLA) and nano-hydroxyapatite (n-HA) have been recognized as excellent candidate material in bone repai The difference in hydrophilicity/hydrophobicity and poor interfacial compatibility between n-HA filler and PLA matrix leads to non-uniform dispersion of n-HA in PLA matrix and consequent poor reinforcement effect. In this study, an HA/PLA nanocomposite was designed based on the surface modification of n-HA with poly(D-lactide) (PDLA), which not only can improve the dispersion of n-HA in the poly(L-lactide) (PLLA) matrix but also could form a stereocomplex crystal with the matrix PLLA at the interface and ultimately lead to greatly enhanced mechanical performance The n-HA/PLA composites were characterized by means of scanning electron microscopy, Fourier transform infrared spectroscopy, X-Ray diffraction, thermal gravity analysis, differential scanning calorimetry, and a mechanical test; in vitro cytotoxicity of the composite material as well as its efficacy in inducing osteogenic differentiation of rat bone marrow stromal cells (rMSCs) were also evaluated. Compared with those of neat PLLA, the tensile strength, Young’s modulus, interfacial shear strength, elongation at break and crystallinity of the composites increased by 34%, 53%, 26%, 70%, and 17%, respectively. The adhesion and proliferation as well as the osteogenic differentiation of rMSCs on HA/PLA composites were clearly evidenced. Therefore, the HA/PLA composites have great potential for bone repai.

A bioactive poly(ether-ether-ketone) nanocomposite scaffold regulates osteoblast/osteoclast activity for the regeneration of osteoporotic bone.

Due to the lower regeneration capacity of the osteoporotic bone, the treatment of osteoporotic defects is extremely challenging in clinics. In this study, strontium-doped bioactive glass nanoparticles loaded with sodium alendronate (ALN), namely A-SrBG, were incorporated into the poly(ether-ether-ketone) matrix to fabricate a bioactive composite scaffold (ASP), which was expected to both inhibit bone resorption and promote bone regeneration. The results showed that such a composite scaffold with interconnected macropores (200-400 μm) could release Ca2+, Sr2+, and ALN in vitro. The proliferation, alkaline phosphatase (ALP) activity, expression of osteogenesis-related genes, and formation of calcified nodules of rat bone marrow stromal cells (rBMSCs) were clearly evidenced, and the reduction in the proliferation, tartrate-resistant acid phosphatase (TRAP) activity, cell fusion, and expression of osteoclastogenesis-related genes of osteoclasts was observed as well. In the presence of the ASP scaffold, enhanced osteogenesis along with inhibiting osteoclastogenesis was observed by modulating the osteoprotegerin (OPG)/receptor activator for nuclear factor κB ligand (RANKL) ratio. The efficacy of the composite scaffold in the regeneration of osteoporotic critical-sized cranial defect in a rat model was evaluated. Therefore, the bioactive composite scaffold with excellent biocompatibility and osteogenic potential could be a promising material for the repair of osteoporotic bone defects.

Promoting osseointegration of titanium implants through magnesium- and strontium-doped hierarchically structured coating

This study aimed to investigate the effect of magnesium (Mg) and strontium (Sr) surface modification on osseointegration of titanium (Ti) implants with a hierarchically structured coating. Mg- and Sr-doped hierarchical surface coating has been fabricated on Ti implant through the hydrothermal method. Scanning electron microscopy (SEM), atomic force microscopy (AFM), energy dispersive spectrometer (EDS), inductively coupled plasma/optical emission spectroscopy (ICP-OES) and contact-angle measurement have been applied to characterize the surface coating. The biocompatibility and osseointegration of Ti implants with Mg- and Sr-dropped hierarchical coating have been assessed in vivo using a rat tibia implantation model. The proposed mechanism that improves osteointegration of Mg- and Sr-doped coating Ti implant has been evaluated by culturing rat bone marrow stromal cells (BMSCs) alone or co-culturing Schwann cells (SCs) and BMSCs on the coating surfaces. Our results proved that both Mg- and Sr-doped hierarchical coating could promote osseointegration with Mg exerted a stronger effect in vivo. The in vitro outcomes showed that Mg-doped coating enhances BMSCs adhesion, while the Sr-doped surface promotes osteogenic differentiation of BMSCs. Furthermore, when BMSCs were cultured with SCs, Mg-dropped surfaces accelerated not only the adhesion but also osteogenic differentiation of BMSCs. Conclusively, the hierarchical surface coating with trace element modification can provide a strong guarantee for endosseous applications of titanium (Ti) implants, and Mg-doped hierarchical coating is more effective in promoting osseointegration than Sr modification.