Preparation of an injectable and photocurable carboxymethyl cellulose/hydroxyapatite composite and its application in cranial regeneration.

Limited bone regeneration, uncontrollable degradation rate, mismatched defect zone and poor operability have plagued the reconstruction of irregular bone defect by tissue-engineered materials. A combination of biomimetic scaffolds with hydroxyapatite has gained great popularity in promoting bone regeneration. Therefore, we designed an injectable, photocurable and in-situ curing hydrogel by methacrylic anhydride -modified carboxymethyl cellulose (CMC-MA) loading with spherical hydroxyapatite (HA) to highly simulate the natural bony matrix and match any shape of damaged tissue. The prepared carboxymethyl cellulose-methacrylate/ hydroxyapatite(CMC-MA/HA) composite presented good rheological behavior, swelling ratio and mechanical property under light illumination. Meanwhile, this composite hydrogel promoted effectively proliferation, supported adhesion and upregulated the osteogenic-related genes expression of MC3T3-E1 cells in vitro, as well as the activity of the osteogenic critical protein, Integrin α1, ß1, Myosin 9, Myosin 10, BMP-2 and Smad 1 in Integrin/BMP-2 signal pathway. Together, the composite hydrogels realized promotion of bone regeneration, deformity improvement, and the enhanced new bone strength in skull defect. It also displayed a good histocompatibility and stability of subcutaneous implantation in vivo. Overall, this study laid the groundwork for future research into developing a novel biomaterial and a minimally invasive therapeutic strategies for reconstructing bone defects and contour deficiencies.

Periodontium-Mimicking, Multifunctional Biomass-Based Hydrogel Promotes Full-Course Socket Healing.

Preserving stable tooth-periodontal tissue integration is vital for maintaining alveolar bone stability under physiological conditions. However, tooth extraction compromises this integration and impedes socket healing. Therefore, it becomes crucial to provide early stage coverage of the socket to promote optimal healing. Drawing inspiration from the periodontium, we have developed a quaternized methacryloyl chitosan/dopamine-grafted oxidized sodium alginate hydrogel, termed the quaternized methacryloyl chitosan/dopamine-grafted oxidized sodium alginate hydrogel (QDL hydrogel). Through blue-light-induced cross-linking, the QDL hydrogel serves as a comprehensive wound dressing for socket healing. The QDL hydrogel exhibits remarkable efficacy in closing irregular tooth extraction wounds. Its favorable mechanical properties, flexible formability, and strong adhesion are achieved through modifications of chitosan and sodium alginate derived from biomass sources. Moreover, the QDL hydrogel demonstrates a superior hemostatic ability, facilitating swift blood clot formation. Additionally, the inherent antibacterial properties of the QDL hydrogel effectively inhibit oral microorganisms. Furthermore, the QDL hydrogel promotes angiogenesis, which facilitates the nutrient supply for subsequent tissue regeneration. Notably, the hydrogel accelerates socket healing by upregulating the expression of genes associated with wound healing. In conclusion, the periodontium-mimicking multifunctional hydrogel exhibits significant potential as a clinical tooth extraction wound dressing.

Facile Preparation of a Multifunctional Hydrogel Composite Dressing via Dual Self-Redox Mechanism for Accelerated Infected Wound Healing.

The management of infected wound healing remains a formidable challenge primarily due to the absence of an ideal wound dressing that can not only effectively inhibit persistent bacterial infection and mitigate excessive inflammation but also possess appropriate mechanical strength, moderate adhesiveness, and favorable self-healability to maintain its protective function and facilitate easy change. In this study, we present an effective strategy for the preparation of a novel composite hydrogel under mild conditions, without the need for additives. This is achieved by incorporating resveratrol (RSV)-loaded alkali lignin nanoparticles (ARNPs) into an advanced polyacrylamide-based hydrogel matrix. The utilization of ARNPs facilitated the sustained release of RSV, thereby enhancing its bioavailability. The polymerization of acrylamide was gently triggered by free radicals generated through a novel dual self-redox mechanism involving silver ions (Ag+), catechols, and ammonium persulfate in neutral and at room temperature, without the requirement of cross-linkers. The dual self-redox reactions played a dominant role in facilitating the gelation process and imparting the desired properties to the resulting hydrogels. The obtained product exhibited exceptional antibacterial properties, favorable anti-inflammatory activity, superior tensile strength, moderate adhesiveness, and reliable self-healability, thereby accelerating the closure of infected wounds. Collectively, this study synergistically integrated RSV-sustained release nanoparticles and a specially designed multifunctional hydrogel into a single system in a conveniently manipulable manner. This composite wound dressing material holds promise for promoting the healing of infected wounds and has potential applications in other complex wound treatments.

Intratumor delivery of amino-modified graphene oxide as a multifunctional photothermal agent for efficient antitumor phototherapy.

Due to the high selectivity and non-invasive property, phototherapy has attracted increasing attention in the treatment of cancer. Targeted delivery and retention of photoactive agents in tumor tissue is of great significance and importance for safe and efficient phototherapy. Herein, we report a multifunctional nanomaterial photothermal agent, namely amino-modified graphene oxide (AGO) for anti-oral cancer photothermal therapy (PTT). Compared to the parental graphene oxide (GO) which has a negative charge and weak photothermal effect, AGO possesses a positive charge (∼+50 mV) and the significantly enhanced photothermal effect. Positive charge allows AGO to efficiently interact with tumor cells and retain in tumor tissue after intratumor injection. The enhanced photothermal effect allows AGO to achieve the tunable and efficient PTT. In vitro results show that AGO (15 µg/mL) reduces the viability of HSC-3 cells (oral squamous cell carcinoma cell line) to 5% under near infrared (NIR) irradiation (temperature increased to 58.4 °C). In vivo antitumor study shows that intratumor delivery of AGO (200 µg/mouse) has no inhibition effects on tumor growth (454% of initial tumor size) without NIR. With a single dose of NIR irradiation, however, AGO significantly reduces the tumor size to 25% of initial size in 1 of 4 mice, and even induces the complete tumor ablation in 3 of 4 mice. Furthermore, the injected AGO falls off along with the scab after PTT. Our findings indicate that AGO is a potential nano-photothermal agent for tunable, convenient and efficient anticancer PTT.

Effect of dental follicles in minimally invasive open-eruption technique of labially impacted maxillary central incisors.

OBJECTIVES: To summarize the open-eruption technique of impacted anterior maxillary teeth, this study reports a technically improved operation on surgical exposure based on dental follicles and evaluates post-treatment periodontal health considering the effect of dental follicles. METHODS: Patients who underwent open-eruption technique with unilateral labially impacted maxillary central incisors were selected. The impacted teeth were assigned to the experimental group, and the contralateral unimpacted maxillary central incisors were assigned to the control group. In the surgical exposure, the new technique makes use of dental follicles to manage the soft tissue, so as to preserve soft tissue for better aesthetic results and healthier periodontal tissue. Tooth length, root length, alveolar bone loss, and alveolar bone thickness were recorded after the therapy. RESULTS: A total of 17 patients with unilateral maxillary central incisor impaction were successfully treated. The tooth length and root length of the two groups showed a statistically significant difference between the impacted and homonym teeth, with a shorter length in the impacted tooth (P<0.05). More labial alveolar bone loss was found in the experimental group compared with that in the control group (P<0.05). The outcomes of the cementoenamel junction width, pa- latal alveolar bone loss, and alveolar bone thickness did not indicate statistical significance between the experimental and control groups (P>0.05). CONCLUSIONS: In the surgical exposure, the new technique uses dental follicles to manage the soft tissue and preserve it for better aesthetic results and healthier periodontal tissues.

Genesis of osteoclasts on calcium phosphate ceramics and their role in material-induced bone formation.

Innate immune responses play important roles in material-induced bone formation and such roles were further explored in the current study with an emphasis on M2 macrophages and osteoclastogenesis. With the presence of M-CSF and RANKL, M0 macrophages from FVB mouse bone marrow-derived monocytes (BMMs) fused to osteoclasts with both M2 marker and osteoclast marker at day 5, and such osteoclast formation at day 5 was enhanced when the cells were treated with IL-4 at day 3. With IL-4 treatment alone for 24 h, M0 polarized into M2 macrophages. Conditioned medium of M2 macrophages enhanced osteogenic differentiation of MC3T3-E1 (pre-osteoblasts) while osteoclast conditioned medium enhanced osteogenic differentiation of CRL-12424 (osteogenic precursors). TCPs (a typical osteoinductive material) supported M2 macrophage polarization at day 4 and osteoclast formation at day 5, while TCPb (a typical non-osteoinductive material) was less effective. Moreover, osteoclasts formed on TCPs produced osteogenic factors including S1P, Wnt10B and BMP-6, resulting osteogenic differentiation of CRL-12424 cells. Similar to in vitro testing, TCPs favored M2 macrophage polarization followed by the formation of osteoclasts in vivo, as compared to TCPb. The overall data provided evidence of a coupling between M2 macrophages, osteoclasts and material-induced bone formation: osteoclasts formed from M2 macrophages secrete osteogenic cytokines to induce osteogenic differentiation of osteogenic precursor cells to finally form bone. The current findings outlined a biological mechanism of material-induced bone formation and further rationalized the use of osteoinductive materials for bone regeneration. STATEMENT OF SIGNIFICANCE: This paper provides evidence for finding out the relationship between M2 macrophages, osteoclasts and osteogenesis in material-induced bone formation. It suggested that osteoinductive materials enhanced macrophage polarization to M2 macrophages which fuses to osteoclasts, osteoclasts subsequently secret osteogenic cytokines to differentiate finally osteogenic precursors to form bone in osteoinductive materials. The data supports scientifically the superiority of osteoinductive materials for bone regeneration in clinics.

Hypoxia inducible factor-1 signaling pathway in macrophage involved angiogenesis in materials-instructed osteo-induction.

Although osteo-inductive materials are regarded as promising candidates for critical-sized bone repair, their clinical application is limited by ambiguous mechanisms. The hypoxia-inducible factor (HIF)-1 signaling pathway, which responds to hypoxic conditions, is involved in both angiogenesis and osteogenesis. Strategies harnessing HIF-1 signaling to promote angiogenesis have been applied and have succeeded in repairing segmental bone defects. Meanwhile, macrophages have been shown to have important immunoregulatory effects on material-induced osteo-induction and correlate with HIF-1 activity. Thus, it is reasonable to assume that HIF-activated macrophages may also play important roles in the angiogenesis of material-induced osteo-induction. To verify this assumption, a classical type of osteo-inductive calcium phosphate (TCPs) was utilized. First, using RNA sequencing, we found that hypoxia activated the HIF signaling pathway in macrophages, which contributed to angiogenesis in TCPs. In addition, after treatment with a conditioned medium extracted from the co-culture system of macrophages and TCPs under hypoxic conditions, the migration and tube formation ability of human umbilical vein endothelial cells (HUVECs) significantly increased. In vivo, inhibition of HIF-1 or clearance of macrophages could result in impaired angiogenesis in TCPs. Finally, more blood vessels were formed in the TCPs group than in the control group. In conclusion, this study elucidated the vital role of the HIF signaling pathway in infiltrating macrophages during early vessel growth in material-induced osteo-induction. It is beneficial in advancing the exploration of the related mechanism and providing possible support for optimizing the applicability of osteo-inductive materials in bone repair.

HIF signaling: A new propellant in bone regeneration.

Bone tissue destruction leads to severe pain, physical flaws, and loss of motility. Bone repair using biocompatible and osteo-inductive scaffolds is regarded as a viable and potential therapeutic approach. However, for large-scale bone regeneration, oxygen and nutrient supply have become limiting factors. Further, a considerable need exists for recruited cell activities and blood vessel growth. Hypoxia-inducible factor (HIF) signaling pathways induced by hypoxia are involved in angiogenesis and osteogenesis. As an important transcription factor, HIF-1 functions by modulating vital genes, such as VEGF, PDK1, and EPO, and is a crucial regulator that influences the final fate of bone regeneration. Collectively, to achieve better osteogenesis results, the in-depth molecular mechanisms that underpin the links between materials, cells, and HIF signaling pathways must be determined. This review aimed to provide an in-depth insight into recent progress in HIF-regulated bone regeneration. Hypoxia and cellular oxygen-sensing mechanisms and their correlations with osteogenesis were determined, and recent studies on hypoxia-inducing and hypoxia-mimicking strategies were briefly described. Finally, the potential applications of HIF signaling in bone regeneration were highlighted. This review provides theoretical support for establishing a novel and viable bone repair strategy in the clinic by harnessing HIF signaling.

Grafting resveratrol onto mesoporous silica nanoparticles towards efficient sustainable immunoregulation and insulin resistance alleviation for diabetic periodontitis therapy.

Host-modulation therapy is generally accepted as a novel promising method for diabetic periodontitis (DP) treatment and screening an appropriate drug model is the key to success. Resveratrol (RSV), because of its viable antioxidative and anti-inflammatory properties and its ability to control glucose metabolism, is considered a potential candidate. However, poor water solubility, rapid decomposition and short serum half-life period significantly limit its application. Therefore, in this study, we designed a RSV-grafted mesoporous silica nanoparticle (MSN-RSV) drug carrier system to enhance RSV's stability effectively and prolong its duration. Further analyses have verified the indispensable role of MSNs in improving the bioavailability of RSV, which could result in a more favorable therapeutic efficacy in DP related to regulating the polarization of the macrophage. The reason for this could be explained by activating the SIRT1/AMPK signaling pathway and inhibiting the NF-κB signaling pathway. This study also focused on the auxiliary effect of MSN-RSV on alleviating insulin resistance (IR) and controlling glucose metabolism. In brief, the study has provided a potential alternative strategy for DP therapy. It is also helpful for future intensive research topics like the immunoregulatory mechanisms in the bidirectional relationship between diabetes and periodontitis.

The biological effect of recombinant humanized collagen on damaged skin induced by UV-photoaging: An in vivo study.

The application of medical devices to repair skin damage is clinically accepted and natural polymer enjoys an important role in this field, such as collagen or hyaluronic acid, etc. However, the biosafety and efficacy of these implants are still challenged. In this study, a skin damage animal model was prepared by UV-photoaging and recombinant humanized type III collagen (rhCol III) was applied as a bioactive material to implant in vivo to study its biological effect, comparing with saline and uncrosslinked hyaluronic acid (HA). Animal skin conditions were non-invasively and dynamically monitored during the 8 weeks experiment. Histological observation, specific gene expression and other molecular biological methods were applied by the end of the animal experiment. The results indicated that rhCol III could alleviate the skin photoaging caused by UV radiation, including reduce the thickening of epidermis and dermis, increase the secretion of Collagen I (Col I) and Collagen III (Col III) and remodel of extracellular matrix (ECM). Although the cell-material interaction and mechanism need more investigation, the effect of rhCol III on damaged skin was discussed from influence on cells, reconstruction of ECM, and stimulus of small biological molecules based on current results. In conclusion, our findings provided rigorous biosafety information of rhCol III and approved its potential in skin repair and regeneration. Although enormous efforts still need to be made to achieve successful translation from bench to clinic, the recombinant humanized collagen showed superiorities from both safety and efficacy aspects.

Analysis of the willingness of community residents of Chengdu city to participate in various modes of family dental services and the factors influencing their decision.

OBJECTIVES: To determine the various modes of family dental services available in Chengdu city, China and to analyze the willingness of community residents to sign the contract for these services and the factors influencing their decision to do so. METHODS: From September 2020 to October 2020, nine communities in Chengdu city were sampled via stratified multiple-stage random sampling and surveyed by sending questionnaires. The questionnaire sought to gather information on the residents' sociodemographic characteristics, their intention to participate in family dental services, and determine their knowledge of oral health cognition and behavior. RESULTS: A total of 1 227 valid questionnaires were collected. Among the community residents surveyed, 24.78% stated that they were willing to participate in family dental services. Binary logistic regression analysis revealed that the factors affecting the residents' willingness to participate in various modes of family dental services were age (OR=0.571, P<0.05), type of medical insurance (OR=1.534, P<0.05), level of oral health knowledge (OR=1.363, P<0.05), oral health behavior [including the number of time they brush their teeth (OR=1.464, P<0.05), and the frequency of seeking oral medical treatment(OR=1.780, 2.174, P<0.05)]. CONCLUSIONS: The demand of community residents for the family dental services needs to be improved. Young and middle-aged people showed more enthusiasm than older adults to seek family dental services. The type of medical insurance they have and the level of their health literacy were the primary factors that influence their decision to seek such services. Information and education campaigns on oral health should be strengthened to enhance the public's knowledge of this important aspect of hygiene and overall health and promote the development of various modes of family dental services.

Dental follicles promote soft tissue management in surgical exposure of labially impacted maxillary canine.

BACKGROUND: The present study aimed to report a technically improved operation on the surgical exposure of labially impacted maxillary canine, elaborating the management of soft tissue to achieve better aesthetic results, and post-treatment periodontal health. METHODS: Patients sought orthodontic treatment with unilateral labially impacted maxillary canines were selected in this study. The impacted teeth were assigned to the experimental group and contralateral unimpacted canines were assigned to the control group. The impacted canines were surgically exposed with dissected dental follicle (DF) stitching to muscle and mucosa surrounding the crowns. The gingival index (GI), probing depth (PD), the width of the keratinized gingiva (WKG), gingival scars (GS), bone loss (BL), and apical root resorption (ARR) were recorded after the removal of the fixed appliance. A two-sample t-test was used for independent samples for parametric variables. RESULTS: A total of 24 patients with unilateral maxillary canine impaction were successfully treated. The outcomes of GI, WKG, GS, BL, and ARR did not indicate statistical significance between the experimental group and the control group. CONCLUSIONS: The preservation of DF promotes soft tissue management in combined surgical and orthodontic treatment of labially impacted maxillary canine to achieve better periodontal status. Trial Registration Chinese Clinical Trial Registry ChiCTR2000029091, 2020-01-12.

Three-dimensional printed model of impacted third molar for surgical extraction training.

OBJECTIVES: Extraction of impacted mandibular third molars is one of the most common surgical procedures performed at dental clinics; however effective training models for teaching oral surgery to dental students are limited. This study aimed to use three-dimension (3D) printing technology to develop an effective training model for impacted third molar extraction. METHODS: The data for the 3D model were digitally processed using high-resolution computed tomography, and two common, but different patterns of impacted third molars were simulated using computer-aided design. Thereafter, the model was printed using the 3D-printing technology, and the efficiency of the 3D-printed model and an animal model (pig mandible) were compared using a five-point Likert scale by 35 oral surgeons in the oral surgery department and 208 students of stomatology in the internship stage. RESULTS: The 3D-printed model consisted of three parts: a non-replaceable part (i.e., the body of the mandible and the teeth from the left first molar to the right first molar) and two replaceable parts (i.e., the part of the ascending ramus of the mandible, as well as the second and third molars). It was covered with a layer of rubber-like material to simulate the gingiva. For the comparison between the 3D-printed and animal models, a total of 205 questionnaires were collected. Both oral surgeons and students agreed that the 3D-printed model was better than the animal model in terms of total value and the anatomy of the bone and teeth, simulating the surgical procedure (p < 0.05), while the two models achieved similar results for haptic feedback of the soft tissue (p > 0.05). CONCLUSIONS: The 3D-printed model is realistic and effective for learning impacted third molar extraction and received positive feedback from students and oral surgeons. This model can significantly improve the pre-clinical skill training of dental students.

Serial cellular events in bone formation initiated by calcium phosphate ceramics.

To better understand the biological mechanisms triggered by osteoinductive materials in vivo, we evaluated the timeline of cellular responses to osteoinductive materials subcutaneously implanted in FVB mice. More F4/80-positive macrophages were present in osteoinductive tri-CaP ceramic (TCP) with submicron surface topography (TCPs) than non-osteoinductive TCP with micron surface topography (TCPb) at week 1. Moreover, TCPs (but not TCPb) significantly enhanced osteoclastogenesis, and induced macrophages to polarize from M1 to M2 in the first week. The time sequence and relevance of macrophages and osteoclasts responses involved in bone formation was then evaluated through peri-implant injection of specific chemicals in mice implanted with osteoinductive TCPs. Day-1 injection of clodronate liposomes (LipClod) depleted macrophages, inhibited macrophage polarization to M2, blocked osteoclastogenesis and bone formation, while the day-6 injection was less effective. Anti-RANKL antibody (aRANKL) did not affect macrophage colonization but inhibited osteoclastogenesis. Injection of aRANKL before week 2 aborted bone formation in TCPs, while injection at week 4 partially inhibited bone formation. The overall data show that following ectopic implantation, osteoinductive materials allow macrophage colonization in hours to days, macrophage polarization to M2 in days (within 7 days), osteoclastogenesis in weeks (e.g. in 2 weeks) and bone formation thereafter (after 4 weeks). The serial cellular events verified herein bring a new insight on material-induced bone formation and pave the way to further explore the mechanisms triggered by osteoinductive materials. STATEMENT OF SIGNIFICANCE: A series of key cellular events triggered by osteoinductive calcium phosphate ceramic was revealed: macrophages colonized within hours to days, polarization of M2 macrophages occurred within 7 days, osteoclastogenesis mainly occurred in weeks (e.g. in 2 weeks) and bone formation finally arose thereafter (after 4 weeks). Moreover, such time sequence of cellular events was confirmed with specific chemicals (clodronate liposomes and anti-RANKL antibody). The findings verified herein bring a new insight on material-induced bone formation and pave the way to further explore the mechanisms triggered by osteoinductive materials.

An injectable and antibacterial calcium phosphate scaffold inhibiting Staphylococcus aureus and supporting stem cells for bone regeneration.

Staphylococcus aureus (S. aureus) is the major pathogen for osteomyelitis, which can lead to bone necrosis and destruction. There has been no report on antibacterial calcium phosphate cement (CPC) against S. aureus. The aims of this study were to: (1) develop novel antibacterial CPC-chitosan-alginate microbead scaffold; (2) investigate mechanical and antibacterial properties of CPC-chitosan-penicillin-alginate scaffold; (3) evaluate the encapsulation and delivery of human umbilical cord mesenchymal stem cells (hUCMSCs). Flexural strength, elastic modulus and work-of-fracture of the CPC-chitosan-penicillin-alginate microbeads scaffold and CPC-chitosan scaffold were evaluated. Penicillin release profile and antibacterial effects on S. aureus were determined. The hUCMSC delivery and release from penicillin-alginate microbeads were investigated. Injectable CPC-chitosan-penicillin-alginate microbeads scaffold was developed for the first time. CPC-chitosan-penicillin-alginate microbeads scaffold had a flexural strength of 3.16 ± 0.55 MPa, matching that of cancellous bone. With sustained penicillin release, the new scaffold had strong antibacterial effects on S. aureus, with an inhibition zone diameter of 32.2 ± 2.5 mm, greater than that of penicillin disk control (15.1 ± 2.0 mm) (p < 0.05). Furthermore, this injectable and antibacterial scaffold had no toxic effects, yielding excellent hUCMSC viability, which was similar to that of CPC control without antibacterial activity (p > 0.05). CPC-chitosan-penicillin-microbeads scaffold had injectability, good strength, strong antibacterial effects, and good biocompatibility to support stem cell viability for osteogenesis. CPC-chitosan-penicillin-microbeads scaffold is promising for dental, craniofacial and orthopedic applications to combat infections and promote bone regeneration.

Controlled Delivery of Growth Factor by Hierarchical Nanostructured Core-Shell Nanofibers for the Efficient Repair of Critical-Sized Rat Calvarial Defect.

Electrospun nanofibers have received much attention as bone tissue-engineered scaffolds for their capacity to mimic the structure of natural extracellular matrix (ECM). Most studies have reproduced nanofibers with smooth surface for tissue engineering. This is quite different from the triple-helical nanotopography of natural collagen nanofibrils. In this study, hierarchical nanostructures were coated on the surface of drug-loaded core-shell nanofibers to mimic natural collagen nanofibrils. The nanoshish-kebab (SK) structure was decorated regularly on the surface of the nanofibers, and the inner-loaded bone morphogenetic protein 2 (BMP2) exhibited a gentle release pattern, similar to a zero-order release pattern in kinetics. The in vitro study also showed that the SK structure could accelerate cell proliferation, attachment, and osteogenic differentiation. Four groups of scaffolds were implanted in vivo to repair critical-sized rat calvarial defects: (1) PCL/PVA (control); (2) SK-PCL/PVA; (3) PCL/PVA-BMP2; and (4) SK-PCL/PVA-BMP2. Much more bone was formed in the SK-PCL/PVA group (24.57 ± 3.81%) than in the control group (1.21 ± 0.23%). The BMP2-loaded core-shell nanofibers with nanopatterned structure (SK-PCL/PVA-BMP2) displayed the best repair efficacy (76.38 ± 4.13%), followed by the PCL/PVA-BMP2 group (39.86 ± 5.74%). It was believed that the hierarchical nanostructured core-shell nanofibers could promote osteogeneration and that the SK structure showed synergistic ability with nanofiber-loaded BMP2 in vivo for bone regeneration. Thus, this BMP2-loaded core-shell nanofiber scaffold with hierarchical nanostructure holds great potential for bone tissue engineering applications.

The Emerging Roles of Long Noncoding RNAs in Bone Homeostasis and Their Potential Application in Bone-Related Diseases.

Increasing evidence has announced the emerging roles of long noncoding RNAs (lncRNAs) in modulating bone homeostasis due to their potential regulating effects on bone-related cells' proliferation, migration, differentiation and apoptosis. Thus, lncRNAs have been considered as a promising gene tool to facilitate the bone regeneration process and then to predict and cure bone-related diseases such as osteosarcoma, osteoporosis, and osteoarthritis. In this review, we first enumerated several kinds of dysregulated lncRNAs and concisely summarized their regulating role in bone formation as well as resorption process. The related mechanisms were also discussed, respectively. Then, the positive or negative behavior of these lncRNAs in bone-related diseases was elucidated. This review provides an in-depth sight about the lncRNA's clinical values and limitations, which is conducive to explore new gene targets and further establish new therapeutic strategies for bone-related disease.

The synergetic effect of bioactive molecule-loaded electrospun core-shell fibres for reconstruction of critical-sized calvarial bone defect-The effect of synergetic release on bone Formation.

OBJECTIVES: Bone regeneration is a complex process modulated by multiple growth factors and hormones during long regeneration period; thus, designing biomaterials with the capacity to deliver multiple bioactive molecules and obtain sustained release has gained an increasing popularity in recent years. This study is aimed to evaluate the effect of a novel core-shell electrospun fibre loaded with dexamethasone (DEX) and bone morphogenetic protein-2 (BMP-2) on bone regeneration. MATERIALS AND METHODS: The core-shell electrospun fibres were fabricated by coaxial electrospinning technology, which were composed of poly-D, L-lactide (PLA) shell and poly (ethylene glycol) (PEG) core embedded with BMP-2 and DEX-loaded micelles. Morphology, hydrophilicity, gradation, release profile of BMP-2 and DEX, and cytological behaviour on bone marrow mesenchymal stem cells (BMSCs) were characterized. Furthermore, the effect on bone regeneration was evaluated via critical-sized calvarial defect model. RESULTS: The electrospun fibres were featured by the core-shell fibrous architecture and a suitable degradation rate. The sustained release of DEX and BMP-2 was up to 562 hours. The osteogenic gene expression and calcium deposition of BMSCs were significantly enhanced, indicating the osteoinduction capacity of electrospun fibres. This core-shell fibre could accelerate repair of calvarial defects in vivo via synergistic effect. CONCLUSIONS: This core-shell electrospun fibre loaded with DEX and BMP-2 can act synergistically to enhance bone regeneration, which stands as a strong potential candidate for repairing bone defects.

Macrophage polarization plays roles in bone formation instructed by calcium phosphate ceramics.

To investigate the roles of macrophages in material-instructed bone formation, two calcium phosphate (TCP) ceramics with the same chemistry but various scales of surface topography were employed in this study. After being implanted subcutaneously in FVB mice for 8 weeks, TCPs (TCP ceramics with submicron surface topography) gave rise to bone formation, while TCPb (TCP ceramics with micron surface topography) did not, showing the crucial role of surface topography scale in material-instructed bone formation. Depletion of macrophages with liposomal clodronate (LipClod) blocked such bone formation instructed by TCPs, confirming the role of macrophages in material-instructed bone formation. Macrophage cells (i.e. RAW 264.7 cells) cultured on TCPs in vitro polarized to tissue repair macrophages as evidenced by gene expression and cytokine production, while polarizing to pro-inflammatory macrophages on TCPb. Submicron surface topography of TCP ceramics directed macrophage polarization via PI3K/AKT pathways with the synergistic regulation of integrin ß1. Finally, the tissue repair macrophage polarization on TCPs resulted in osteogenic differentiation of mesenchymal stem cells in vitro. At early implantation in FVB mice, TCPs recruited more macrophages which polarized towards tissue repair macrophages with time. The present data demonstrate the important roles of macrophage polarization in bone formation instructed by calcium phosphate ceramics.

Experimental and simulation studies of strontium/fluoride-codoped hydroxyapatite nanoparticles with osteogenic and antibacterial activities.

Multiple ions codoping may effectively modulate physicochemical and biological properties of hydroxyapatite (HA) for diverse biomedical applications. This study synthesized strontium (Sr)-, fluorine (F)- doped, and Sr/F-codoped HA nanoparticles by a hydrothermal method, and investigated the effect of ion doping on characteristics of HA, including crystallinity, crystal size, lattice parameters, and substitution sites by experiments and simulation with density functional theory (DFT) methods. It was found that, Sr doping increased the lattice parameters of HA whereas F doping decreased these parameters. Additionally, F doping enhanced the structural stability of the Sr-doped HA. F doping created excellent antibacterial properties to effectively inhibit growth of Streptococcus mutans. An appropriate Sr doping level endowed HA with optimum osteogenic ability to promote osteoblastic differentiation of bone marrow stem cells. These suggest that, Sr/F codoping is an effective approach to synthesizing HA-based materials with both antibacterial and osteogenic properties. More broadly, HA nanomaterials with specific characteristics may be designed for meeting diverse requirements from biomedical applications.