Dual-energy computed tomography and micro-computed tomography for assessing bone regeneration in a rabbit tibia model.

To gain a more meaningful understanding of bone regeneration, it is essential to select an appropriate assessment method. Micro-computed tomography (Micro-CT) is widely used for bone regeneration because it provides a substantially higher spatial resolution. Dual-energy computed tomography (DECT) ensure shorter scan time and lower radiation doses during quantitative evaluation. Therefore, in this study, DECT and Micro-CT were used to evaluate bone regeneration. We created 18 defects in the tibial plateau of the rabbits and filled them with porous polyetheretherketone implants to promote bone regeneration. At 4, 8, and 12 weeks, Micro-CT and DECT were used to assess the bone repair in the defect region. In comparison to Micro-CT (152 ± 54 mg/cm3), the calcium density values and hydroxyapatite density values obtained by DECT [DECT(Ca) and DECT(HAP)] consistently achieved lower values (59 ± 25 mg/cm3, 126 ± 53 mg/cm3). In addition, there was a good association between DECT and Micro-CT (R = 0.98; R2 = 0.96; DECT(Ca): y = 0.45x-8.31; DECT(HAP): y = 0.95x-17.60). This study highlights the need to use two different imaging methods, each with its advantages and disadvantages, to better understand the bone regeneration process.

Effects of aligned PLGA/SrCSH composite scaffolds on in vitro growth and osteogenic differentiation of human mesenchymal stem cells.

Strontium (Sr) has important functions in bone remodeling. Incorporating strontium-doped α-calcium sulfate hemihydrate (SrCSH) into poly(lactic-co-glycolic acid) (PLGA) fibrous scaffolds were expected to increase its bio-activity and provide a potential material for bone tissue engineering. In the present study, Sr-containing aligned PLGA/SrCSH fibrous scaffolds similar to the architecture of natural bone were prepared via wet spinning. CCK-8 assay revealed that Sr-containing scaffolds possessed better bioactivity and supported favorable cell growth effectively. The aligned PLGA/SrCSH fibers exerted a contact effect on cell attachment, inducing regular cell alignment and influencing a series of cell behaviors. Releasing of high concentration Sr from a-PLGA/SrCSH scaffolds could induce high expression levels of BMP-2, increase ALP activity and upregulate RUNX-2 expression, and further promote the expressions of COL-I and OCN and the maximum mineralization. This study demonstrated that Sr and ordered structure in a-PLGA/SrCSH fibrous scaffolds could synergistically enhance the osteogenic differentiation of umbilical cord mesenchymal stem cells (UCMSCs) by regulating cell arrangement and expressions of osteogenic genes.

Treatment strategies for intrauterine adhesion: focus on the exosomes and hydrogels.

Intrauterine adhesion (IUA), also referred to as Asherman Syndrome (AS), results from uterine trauma in both pregnant and nonpregnant women. The IUA damages the endometrial bottom layer, causing partial or complete occlusion of the uterine cavity. This leads to irregular menstruation, infertility, or repeated abortions. Transcervical adhesion electroreception (TCRA) is frequently used to treat IUA, which greatly lowers the prevalence of adhesions and increases pregnancy rates. Although surgery aims to disentangle the adhesive tissue, it can exacerbate the development of IUA when the degree of adhesion is severer. Therefore, it is critical to develop innovative therapeutic approaches for the prevention of IUA. Endometrial fibrosis is the essence of IUA, and studies have found that the use of different types of mesenchymal stem cells (MSCs) can reduce the risk of endometrial fibrosis and increase the possibility of pregnancy. Recent research has suggested that exosomes derived from MSCs can overcome the limitations of MSCs, such as immunogenicity and tumorigenicity risks, thereby providing new directions for IUA treatment. Moreover, the hydrogel drug delivery system can significantly ameliorate the recurrence rate of adhesions and the intrauterine pregnancy rate of patients, and its potential mechanism in the treatment of IUA has also been studied. It has been shown that the combination of two or more therapeutic schemes has broader application prospects; therefore, this article reviews the pathophysiology of IUA and current treatment strategies, focusing on exosomes combined with hydrogels in the treatment of IUA. Although the use of exosomes and hydrogels has certain challenges in treating IUA, they still provide new promising directions in this field.

Pore size-mediated macrophage M1 to M2 transition affects osseointegration of 3D-printed PEEK scaffolds.

Increasing evidence indicates that macrophages play an important role in angiogenesis and bone regeneration. Because the phenotypic polarization of macrophage is extremely sensitive to the pore size of materials, poly(ether-ether-ketone) (PEEK) scaffolds with pore sizes of 0, 200, and 400 µm were prepared, and the influence of pore size-mediated macrophage polarization on subsequent angiogenesis and osteogenesis was examined. The interaction results of macrophages and scaffolds indicated that macrophages were responsive to the pore size of three-dimensional (3D)-printed PEEK scaffolds, and large pore size scaffolds showed greater potential in inducing M1 to M2 transition of macrophage and enhanced macrophage secretion of high concentrations of osteogenesis-related and angiogenesis-related cytokines. When human umbilical vein endothelial cells (HUVECs) and bone marrow mesenchymal stem cells (BMSCs) were cultured in the conditioned medium derived from co-culture of macrophages and scaffolds, HUVECs showed good angiogenic responses in terms of cell migration and angiogenic gene expression, while BMSCs showed good osteogenic differentiation effect in in vitro mineralization and osteogenesis-related gene expression. The results of bone defect repair showed that the bone volume/total volume ratio and trabecular thickness of the large pore size PEEK scaffold were significantly higher, and it had better biomechanical properties and achieved a better osseointegration effect. Our data demonstrate that large-pore PEEK scaffolds promote angiogenesis and osteogenic differentiation in vitro and osseointegration in vivo, most likely because scaffolds with larger pore size are able to mediate a higher degree of M1 to M2 transition in macrophages.

Display of CCL21 on cancer cell membrane through genetic modification using a pH low insertion peptide.

CCL21, a secondary lymphoid tissue chemokine, plays an important role in generating an effective anti-tumor immune response. In this study, a genetically modified CCL21 was developed by inserting a pH low insertion peptide to establish a CCL21-rich microenvironment for tumors. The fusion tag thioredoxin (Trx) was designed and fused at the N-terminal of the recombinant protein to protect it from being irrevocably misfolded in microbial host cells. The prokaryotic expression vector pET32a-CCL21-pHLIP was constructed and successfully expressed in E. coli BL21 (DE3) with a soluble expression form and a molecular weight of ~35 kDa. The induction conditions were optimized to obtain an extremely high yield of 6.7 mg target protein from 31.1 mg total protein. The 6xHis tagged Trx-CCL21-pHLIP was purified using Ni-NTA resin, and it was confirmed using SDS-PAGE and Western blot analyses. Consequently, the Trx-CCL21-pHLIP protein was successfully displayed on the cancer cell surface in a weak acidic microenvironment and showed the same ability as CCL21 in recruiting CCR7-positive cells. Additionally, the CCL21 fusion protein with or without Trx tag showed similar functions. Therefore, the study implies the feasibility of directing a modular genetic method for the development of protein-based drugs.

Liquid crystalline matrix-induced viscoelastic mechanical stimulation modulates activation and phenotypes of macrophage.

Accumulating evidence indicates that the mechanical microenvironment exerts profound influences on inflammation and immune modulation, which are likely to be key factors in successful tissue regeneration. The elastic modulus (Em) of the matrix may be a useful adjustable property to control macrophage activation and the overall inflammatory response. This study constituted a series of Em-tunable liquid crystalline cell model (HpCEs) resembling the viscoelastic characteristic of ECM and explored how mechanical microenvironment induced by liquid crystalline soft matter matrix affected macrophage activation and phenotypes. We have shown that HpCEs prepared in this work exhibited typical cholesteric liquid crystal phase and distinct viscoelastic rheological characteristics. All liquid crystalline HpCE matrices facilitated macrophages growth and maintained cell activity. Macrophages in lower-Em HpCE matrices were more likely to polarize toward the pro-inflammatory M1 phenotype. Conversely, the higher-Em HpCEs induced macrophages into an elongated shape and upregulated M2-related markers. Furthermore, the higher-Em HpCEs (HpCE-O1, HpCE-H2, HpCE-H1) could coax sequential polarization states of RAW264.7 from a classically activated "M1" state toward alternatively activated "M2" state in middle and later stage of cell culture (within 3-7 days in this work), suggesting that the HpCE-based strategies could manipulate the local immune microenvironment and promote the dominance of the pro-inflammatory signals in early stages, while M2 macrophages in later stages. The liquid crystalline soft mode fabricated in this work maybe offer a new design guideline for in vitro cell models and applications.

3D printed strontium-doped calcium phosphate ceramic scaffold enhances early angiogenesis and promotes bone repair through the regulation of macrophage polarization.

The vascularization of bone repair materials is one of the key issues that urgently need to be addressed in the process of bone repair. The changes in macrophage phenotype and function play an important role in the process of vascularization, and endowing bone repair materials with immune regulatory characteristics to enhance angiogenesis is undoubtedly a new strategy to improve the effectiveness of bone repair. In order to improve the effect of tricalcium phosphate (TCP) on vascularization and bone repair, we doped strontium ions (Sr) into TCP (SrTCP) and prepared porous 3D printed SrTCP scaffolds using 3D printing technology, and studied the scaffold mediated macrophage polarization and subsequent vascularization and bone regeneration. The results of the interaction between the scaffold and macrophages showed that the SrTCP scaffold can promote the polarization of macrophages from M1 to M2 and secrete high concentrations of VEGF and PDGF-bb cytokines, which shows excellent angiogenic potential. When human umbilical vein endothelial cells (HUVECs) were co-cultured with macrophage-conditioned medium of SrTCP scaffold, HUVECs exhibited excellent early angiogenesis-promoting effects in terms of scratch healing, angiogenic gene expression, and in vitro tube formation performance. The results of in vivo bone repair experiments showed that the SrTCP scaffold formed a vascular network with high density and quantity in the bone defect area, which could increase the rate of new bone formation and advance the period of bone formation, and finally achieved a better bone repair effect. We observed a cascade effect in which Sr-doped SrTCP scaffold regulate macrophage polarization to enhance angiogenesis and promote bone repair, which may provide a new strategy for the repair of clinical bone defects.

Multi-stage controllable degradation of strontium-doped calcium sulfate hemihydrate-tricalcium phosphate microsphere composite as a substitute for osteoporotic bone defect repairing: degradation behavior and bone response.

Various requirements for the repair of complex bone defects have motivated to development of scaffolds with adjustable degradation rates and biological functions. Tricalcium phosphate (TCP) and calcium sulfate are the most commonly used bone repair materials in the clinic, how to better combine TCP and calcium sulfate and play their greatest advantages in the repair of osteoporotic bone defect is the focus of our research. In this study, a series of scaffolds with multistage-controlled degradation properties composed of strontium-doped calcium sulfate (SrCSH) and strontium-doped tricalcium phosphate (Sr-TCP) microspheres scaffolds were prepared, and their osteogenic activity,in vivodegradation and bone regeneration ability in tibia of osteoporotic rats were evaluated.In vitrostudies revealed that different components of SrCSH/Sr-TCP scaffolds significantly promoted the proliferation and differentiation of MC3T3-E1 cells, which showed a good osteogenic induction activity.In vivodegradation results showed that the degradation time of composite scaffolds could be controlled in a large range (6-12 months) by controlling the porosity and phase composition of Sr-TCP microspheres. The results of osteoporotic femoral defect repair showed that when the degradation rate of scaffold matched with the growth rate of new bone, the parameters such as bone mineral density, bone volume/total volume ratio, trabecular thickness, angiogenesis marker platelet endothelial cell adhesion molecule-1 and new bone formation marker osteocalcin expression were higher, which promoted the rapid repair of osteoporotic bone defects. On the contrary, the slow degradation rate of scaffolds hindered the growth of new bone to a certain extent. This study elucidates the importance of the degradation rate of scaffolds for the repair of osteoporotic bone defects, and the design considerations can be extended to other bone repair materials, which is expected to provide new ideas for the development of tissue engineering materials in the future.

Soft apoptotic-cell-inspired nanoparticles persistently bind to macrophage membranes and promote anti-inflammatory and pro-healing effects.

Macrophages play a key role in inflammation, infection, cancer, and repairing damaged tissues. Thus, modulating macrophages with engineered nanomaterials is an important therapeutic strategy for healing chronic inflammatory injuries. However, designing and manufacturing therapeutic nanomaterials remains challenging. Therefore, in this study, apoptotic-cell-inspired deformable phosphatidylserine (PS)- containing nanoliposomes (D-PSLs) with a Young's modulus (E) of approximately 0.5 kPa were constructed via a facile and scalable method. Compared with similar-sized conventional PSLs with an E of approximately 80 kPa, the d-PSLs had a lower uptake efficacy, a much longer binding time to the cell surface, and induced enhanced anti-inflammatory and pro-healing effects via the synergistic effects of their mechanical stimulus and PS-receptor mediation after recognition by macrophages. In particular, chronic wound healing in diabetic rats showed that d-PSLs can efficiently promote M2-like macrophage polarization, increase the expression of the vascular endothelial marker CD31 and accelerate wound closure. Our findings suggest that soft d-PSLs represent a promising biomimetic nano-therapeutic approach for macrophage immunotherapy for chronic inflammatory injury, and that the mechanical stimulus of nanomaterials significantly affects the receptor-mediated biological responses, which will inspire the design of engineered nanomaterials for biomedical applications. STATEMENT OF SIGNIFICANCE: Macrophages play a significant role in restoring tissue homeostasis by modulating inflammation and wound healing. Specifically, an M1/M2 macrophage imbalance contributes to various inflammatory disorders. However, modulating macrophages with engineered nanomaterials remains a challenge. In this study, apoptotic-cell-inspired deformable phosphatidylserine (PS)- containing nanoliposomes (D-PSLs) were constructed to explore their interactions with macrophages, and evaluate their anti-inflammatory and pro-healing effects on chronic wounds in diabetic rats. We found that soft d-PSLs can persistently bind to macrophage membranes and enhance the anti-inflammatory and pro-healing responses of macrophages, which not only sheds new light on the design of therapeutic biomaterials based on regulating macrophages but also provide a promising biomimetic nano-therapeutic approach for chronic inflammatory injury.

Enhanced cell affinity and osteogenic differentiation of liquid crystal-based substrate via surface bio-functionalization.

Regulation of cell-substrate interactions is an important factor for modulating cell behaviors. Tailoring the physical and chemical properties of the substrates to better mimic the extracellular matrix (ECM) of native tissue is a more effective strategy for enhancing the cell-substrate contact. In current work, we aim at improving surface bioactivity based on the liquid crystalline substrates for the enhancement in cell affinity and osteogenic differentiation. Polydopamine (PDOPA) adhesive coating was used as a reactive platform for the immobilization of chitooligosaccharide (COS) on the octyl hydroxypropyl cellulose ester (OPC) substrate to generate active OPC-PDOPA-COSs liquid crystalline substrates. Results demonstrated that PDOPA-coated OPC surfaces showed remarkably improved hydrophility and increased elastic modulus, leading to better initial cell attachment. Subsequent COS immobilization on the OPC-PDOPA layer could induce promotion of cell proliferation, polarization and cytoskeleton formation. Rat bone marrow mesenchymal stem cells (rBMSCs) seeded on the OPC-PDOPA-COSs showed higher alkaline phosphatase (ALP) activity, calcium deposition, and up-regulated bone-related genes expression, including BMP-2, RUNx-2, COL-I and OCN. In conclusion, surface biofunctionalization on the OPC-based liquid crystalline substrates could come into being the appropriate combination of surface chemistry and liquid crystalline characteristic that simulating in vivo ECM environment, resulting in a favorable support to enhance positive cell-substrate interactions.

Controlled degradation of chitosan-coated strontium-doped calcium sulfate hemihydrate composite cement promotes bone defect repair in osteoporosis rats.

Strontium (Sr)-doped calcium sulfate hemihydrate (SrCSH) bioactive materials have been demonstrated to promote osteoporotic bone repair, being associated with the stimulation of bone formation and a reduction in bone resorption. However, the rapid degradation and absorption of SrCSH affects its clinical value. In order to delay the degradation time of SrCSH and improve the utilization of Sr2+, chitosan (CS)-coated SrCSH microspheres (CS-SrCSH) are prepared by electrostatic interaction between CS and SrCSH. X-ray diffraction analysis verifies that SrCSH coated by CS does not alter the phase composition of the SrCSH. It was observed that CS-SrCSH microspheres have uniform particle size. More importantly, the in vivo and in vitro degradation time of CS-SrCSH microspheres is significantly longer than that of SrCSH, and the release rate of Sr2+ is stable, achieving a sustained release effect. Furthermore, CS-SrCSH-based cement is used to repair critical-sized OVX rat tibial defects. The in vivo results reveal that CS-SrCSH exhibits a long-term capability for osteogenesis, angiogenesis and bone metabolism inhibition. In conclusion, the controllable degradation of CS-SrCSH-based cements described here could be beneficial for the repair of bone defects, especially in the osteoporotic bone.

Strontium-substituted calcium sulfate hemihydrate/hydroxyapatite scaffold enhances bone regeneration by recruiting bone mesenchymal stromal cells.

Fabrication of osteoconductive scaffold with osteoinductive capability and appropriate resorption rate is of great significance for treating bone defects. To achieve this aim, strontium-substituted calcium sulfate hemihydrate (Sr-CSH) and hydroxyapatite (HA) were mixed to develop a novel composite. Sr-CSH containing 5% and 10% strontium was mixed with HA at the weight ratio of 6:4, respectively. Female Sprague-Dawley rats underwent bone defect surgery in left tibia were randomly assigned to three different treatment groups filled with CSH/HA, 5% and 10% Sr-CSH/HA. Micro-CT analysis showed increased new bone formation in 10% Sr-CSH/HA group compared to CSH/HA group. In addition, histological analysis showed large amounts of chondrocytes and osteoblasts within the pores of Sr-CSH/HA composites as a result of the CSH resorption. Further, CFU-F assay demonstrated the increased amount of bone marrow mesenchymal stromal cells (BMSCs) colonies in 10% Sr-CSH/HA group. In primary BMSCs, extraction from Sr-CSH/HA composite significantly increased the migration of cells, up-regulated the expression of osteoblastic marker genes, and increased the area of mineralized nodules. Together, Sr-CSH/HA may promote bone formation by recruiting and stimulating osteogenic differentiation of BMSCs. Therefore, this composite may be proposed as an ideal substitute to repair bone defects.

Diffusive Adhesives for Water-Rich Materials: Strong and Tunable Adhesion Beyond the Interface.

It is notoriously difficult to adhere water-rich materials, such as hydrogels and biological tissues. Existing adhesives usually suffer from weak and nonadjustable adhesion strength, in part because the contact between the adhesive and substrate is largely restrained to the adhesive/substrate interface. In this study, we have attempted to overcome this shortcoming by developing a class of diffusive adhesives (DAs) that can extend adhesion deep into the substrate to maximize the adhesive/substrate contact. The DAs consist of hydrogel matrices and preloaded water-soluble monomers and crosslinkers that can diffuse extensively into the water-rich substrates after adhesive/substrate contact. Polymerization and crosslinking of the monomers are then triggered leading to a bridging network that interpenetrates the DA and substrate skeletons and topologically binds them together. This kind of adhesion, in the absence of adhesive/substrate covalent bonding, is of high strength and toughness, comparable to those of the best-performing natural and artificial adhesives. More importantly, we can precisely tune the adhesion strength on demand by manipulating the diffusion profile. It is envisioned that the DA family could be extended to include a large pool of hydrogel matrices and monomers, and that they could be particularly useful in biological and medical applications.

Steering Coacervation by a Pair of Broad-Spectrum Regulators.

Coacervation is liquid-liquid phase separation ubiquitous in industrial applications and cellular biology. Inspired by cellular manipulation of coacervate droplets such as P granules, we report here a regulatory strategy to manipulate synthetic coacervation in a spatiotemporally controllable manner. Two oppositely charged small molecules are shown to phase separate into coacervate droplets in water as a result of electrostatic attraction, hydrophobic effect, and entropy. We identify a down regulator, ß-cyclodextrin, to disrupt the hydrophobic effect, thus dissolving the droplets, and an up regulator, amylase, to decompose ß-cyclodextrin, thus restoring the droplets. The regulation kinetics is followed in real time on a single-droplet level, revealing diffusion-limited dissolution and reaction-limited condensation, respectively, taking ∼4 s and 2-3 min. Versatility of this strategy to manipulate the coacervation is demonstrated in two aspects: spatially distributed coacervation in virtue of amylase-grafted hydrogel frameworks and coacervate transportation across membranes and hydrogel networks via a disassemble-to-pass strategy. The current regulatory pairs and strategies are anticipated to be general for a wide variety of synthetic self-assembly systems.

The fabrication of biomineralized fiber-aligned PLGA scaffolds and their effect on enhancing osteogenic differentiation of UCMSC cells.

The key factor of scaffold design for bone tissue engineering is to mimic the microenvironment of natural bone extracellular matrix (ECM) and guide cell osteogenic differentiation. The biomineralized fiber-aligned PLGA scaffolds (a-PLGA/CaPs) was developed in this study by mimicking the structure and composition of native bone ECM. The aligned PLGA fibers was prepared by wet spinning and then biomineralized via an alternate immersion method. Introduction of a bioceramic component CaP onto the PLGA fibers led to changes in surface roughness and hydrophilicity, which showed to modulate cell adhesion and cell morphology of umbilical cord mesenchymal stem cells (UCMSCs). It was found that organized actin filaments of UCMSCs cultured on both a-PLGA and a-PLGA/CaP scaffolds appeared to follow contact guidance along the aligned fibers, and those cells grown on a-PLGA/CaP scaffolds exhibited a more polarized cellular morphology. The a-PLGA/CaP scaffold with multicycles of mineralization facilitated the cell attachment on the fiber surfaces and then supported better cell adhesion and contact guidance, leading to enhancement in following proliferation and osteogenic differentiation of UCMSCs. Our results give some insights into the regulation of cell behaviors through design of ECM-mimicking structure and composition and provide an alternative wet-spun fiber-aligned scaffold with HA-mineralized layer for bone tissue engineering application.

Giant capsids from lattice self-assembly of cyclodextrin complexes.

Proteins can readily assemble into rigid, crystalline and functional structures such as viral capsids and bacterial compartments. Despite ongoing advances, it is still a fundamental challenge to design and synthesize protein-mimetic molecules to form crystalline structures. Here we report the lattice self-assembly of cyclodextrin complexes into a variety of capsid-like structures such as lamellae, helical tubes and hollow rhombic dodecahedra. The dodecahedral morphology has not hitherto been observed in self-assembly systems. The tubes can spontaneously encapsulate colloidal particles and liposomes. The dodecahedra and tubes are respectively comparable to and much larger than the largest known virus. In particular, the resemblance to protein assemblies is not limited to morphology but extends to structural rigidity and crystallinity-a well-defined, 2D rhombic lattice of molecular arrangement is strikingly universal for all the observed structures. We propose a simple design rule for the current lattice self-assembly, potentially opening doors for new protein-mimetic materials.

Scaffold composed of porous vancomycin-loaded poly(lactide-co-glycolide) microspheres: A controlled-release drug delivery system with shape-memory effect.

Loading antibiotics in a biodegradable polymer matrix is an excellent way to control its release kinetics, which eliminates side effects caused by conventional administrations of the drug. This approach is especially beneficial for bone regeneration when using a scaffold made of a biodegradable polymer loaded with drug agents capable of controllable releases. In this case, the scaffold serves as a mechanical support to tissue formation and the drug agents may provide biomolecules to assist the tissue formation and/or provide antibiotics to prevent tissues from infections. Towards this goal, we have developed an approach to make vancomycin-loaded poly(lactide-co-glycolide) (PLGA) microspheres, from which we made scaffolds by compression molding. In this article we concentrate on characterizing the porosity and drug release profiles, as well as verifying shape-memory effect of the scaffolds. The scaffold was biodegradable and showed a much slower drug release profile than microspheres. We confirmed that our PLGA scaffolds recovered to their permanent shapes when heated to 45°C. We believe that these scaffolds will find applications in bone regeneration where both the use of antibiotics against infection and accommodation to spatial restrictions may be required.

Vector assembly of colloids on monolayer substrates.

The key to spontaneous and directed assembly is to encode the desired assembly information to building blocks in a programmable and efficient way. In computer graphics, raster graphics encodes images on a single-pixel level, conferring fine details at the expense of large file sizes, whereas vector graphics encrypts shape information into vectors that allow small file sizes and operational transformations. Here, we adapt this raster/vector concept to a 2D colloidal system and realize 'vector assembly' by manipulating particles on a colloidal monolayer substrate with optical tweezers. In contrast to raster assembly that assigns optical tweezers to each particle, vector assembly requires a minimal number of optical tweezers that allow operations like chain elongation and shortening. This vector approach enables simple uniform particles to form a vast collection of colloidal arenes and colloidenes, the spontaneous dissociation of which is achieved with precision and stage-by-stage complexity by simply removing the optical tweezers.

Enhanced bone formation by strontium modified calcium sulfate hemihydrate in ovariectomized rat critical-size calvarial defects.

The development of a new generation of biomaterials with high osteogenic ability for treatment of osteoporotic fractures is being intensively investigated. The objective of this paper was to investigate new bone formation in an ovariectomized rat (OVX rat) calvarial model of critical size bone defects filled with Sr-containing α-calcium sulfate hemihydrate (SrCSH) cement compared to an α-calcium sulfate hemihydrate (α-CSH) cement and empty defect. X-ray diffraction analysis verified the partial substitution of Sr2+ for Ca2+ did not change the phase composition of α-CSH. Scanning electron microscopy showed that Sr-substituted α-CSH significantly increased the surface roughness. The effects of Sr substitution on the biological properties of SrCSH cement were evaluated by adhesion, proliferation, alkaline phosphatase (ALP) activity of osteoblast-like cells MC3T3-E1. The results showed that SrCSHs enhanced MC3T3-E1 cell proliferation, differentiation, and ALP activity. Furthermore, SrCSH cement was used to repair critical-sized OVX rat calvarial defects. The in vivo results revealed that SrCSH had good osteogenic capability and stimulated new blood vessel formation in a critical sized OVX calvarial defect within 12 weeks, suggesting that SrCSH cement has more potential for application in bone tissue regeneration.