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.

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.

The effect of haemostatic agents on early healing of the extraction socket.

AIM: This study aims to explore the effect of two commercially available haemostatic agents (i.e., collagen sponge and oxide cellulose) on early healing of the extraction socket. MATERIAL AND METHODS: In a murine model, bilateral maxillary first molars were extracted and the sockets were filled with or without haemostatic agents. Histology, histomorphometry and immunostaining assays were performed on samples harvested on postextraction day 1, 3, 7 and 14. In vitro studies were also designed to investigate the effect of agents on the dynamics of pH and viability of cells. RESULTS: Early socket healing was delayed by both agents but with different patterns. The migration of cells was impeded by oxide cellulose on postextraction day 1 compared with the collagen and the control group. The proliferation and osteogenic differentiation of cells were delayed by both materials. Moreover, apoptosis of periodontal ligament cells was present in the haemostatic agent groups. These effects are attributed to the compression to periodontal ligament by both agents, the acidic niche caused by oxide cellulose, and the intense foreign body reaction and inflammatory response caused by the agents. CONCLUSIONS: The placement of haemostatic agents delay the early extraction socket healing via different biological mechanism.

Gold nanoparticles in injectable calcium phosphate cement enhance osteogenic differentiation of human dental pulp stem cells.

In this study, a novel calcium phosphate cement containing gold nanoparticles (GNP-CPC) was developed. Its osteogenic induction ability on human dental pulp stem cells (hDPSCs) was investigated for the first time. The incorporation of GNPs improved hDPSCs behavior on CPC, including better cell adhesion (about 2-fold increase in cell spreading) and proliferation, and enhanced osteogenic differentiation (about 2-3-fold increase at 14 days). GNPs endow CPC with micro-nano-structure, thus improving surface properties for cell adhesion and subsequent behaviors. In addition, GNPs released from GNP-CPC were internalized by hDPSCs, as verified by transmission electron microscopy (TEM), thus enhancing cell functions. The culture media containing GNPs enhanced the cellular activities of hDPSCs. This result was consistent with and supported the osteogenic induction results of GNP-CPC. In conclusion, GNP-CPC significantly enhanced the osteogenic functions of hDPSCs. GNPs are promising to modify CPC with nanotopography and work as bioactive additives thus enhance bone regeneration.

Application of Bidirectional Distraction Osteogenesis for the Treatment of Mandibular Micriognathia Caused by Temporomandibular Joint Ankylosis.

BACKGROUND: Temporomandibular joint (TMJ) ankylosis is a joint disorder that refers to bone or fibrous adhesion of the anatomic joint components and the ensuing loss of function. When it happens on children, it is always accompanied by dentofacial deformities. The objective of this study was to describe the authors' experience of bidirectional distraction osteogenesis for the treatment of mandibular deformities caused by TMJ ankylosis. METHODS: Sixteen patients with TMJ ankylosis and severe secondary mandibular deformities were treated with bidirectional distraction osteogenesis and release of joint from January 2013 to December 2015. Clinical outcomes were assessed based on the oral function, radiography, and medical photography. RESULTS: No reankylosis was found during the follow-up period. Sufficient volume and density new bone had been formed after the consolidation period. All patients have maintained stable improvement in oral function during the follow-up period. Most of the patients achieved satisfactory outcomes. CONCLUSIONS: Bidirectional transport distraction osteogenesis technique is a good and effective therapeutic option in treatment of bilateral or unilateral TMJ ankylosis patients associated with mandibular micrognathia.

Impact of Implant Surface Micropatterns on Epithelial Cell Behavior.

PURPOSE: This study investigated the effect of topography on cell behavior by screening polydimethylsiloxane (PDMS) molds with different nanoscale micropatterns to determine the ideal surface characteristics for attachment of human epithelial cells. MATERIALS AND METHODS: A soft PDMS mold with regular dot arrays was fabricated based on an aluminum oxide template with ordered nanotube arrays and used as a substrate for cell culture. Cell proliferation, spread, and morphology, as well as features of the extracellular matrix and the actin cytoskeleton were assessed. DISCUSSION: Cells grown on 100-nm regular dot arrays had the highest proliferation rate and spread, with the longest pseudopodia; they showed robust actin distribution relative to the control group. CONCLUSION: Three-dimensional PDMS microstructures with 100 nm regular dot arrays were the most effective surface for epithelial cell attachment. These findings can aid in the manufacture of superior materials for use in implants to better integrate into recipient tissue.

Preparation and Evaluations of Mangiferin-Loaded PLGA Scaffolds for Alveolar Bone Repair Treatment Under the Diabetic Condition.

The aim of the present study was to prepare and evaluate a sustained-release mangiferin scaffold for improving alveolar bone defect repair in diabetes. Mangiferin-loaded poly(D,L-lactide-co-glycolide) (PLGA) scaffolds were prepared using a freeze-drying technique with ice particles as the porogen material. The produced scaffolds were examined using a scanning electron microscope (SEM). Drug content and drug release were detected using a spectrophotometer. Degradation behaviors were monitored as a measure of weight loss and examined using SEM. Then, the scaffolds were incubated with rat bone marrow stromal cells under the diabetic condition in vitro, and cell viability was assessed using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Afterward, the scaffolds were implanted into alveolar bone defects of diabetic rats, and bone repair was examined using hematoxylin and eosin staining. The fabricated scaffolds showed porous structures, with average pore size range from 111.35 to 169.45 µm. A higher PLGA concentration led to decreased average pore size. A lower PLGA concentration or a higher mangiferin concentration resulted in increased drug content. The prepared scaffolds released mangiferin in a sustained manner with relatively low initial burst during 10 weeks. Their degradation ratios gradually increased as degradation proceeded. The mangiferin-loaded scaffolds attenuated cell viability decrease under the diabetic condition in vitro. Moreover, they increased histological scorings of bone regeneration and improved delayed alveolar bone defect healing in diabetic rats. These results suggest that the produced mangiferin-loaded scaffolds may provide a potential approach in the treatment of impaired alveolar bone healing in diabetes.

Fabrication and Characterization of a Glucose-sensitive Antibacterial Chitosan-Polyethylene Oxide Hydrogel.

A novel glucose-sensitive chitosan-polyethylene oxide (CS/PEO =1:0.5~1:2.5) hydrogel with controlled release of metronidazole (MNZ) was obtained by chemical cross-linking and immobilization of glucose oxidase (GOx). The hydrogel was characterized by Fourier-transformed infrared spectroscopy (FTIR), compressive mechanical test, rheological analysis, cytotoxicity test, and antibacterial test against Porphyromonas gingivalis. The study found that the CS-PEO composite hydrogel possessed significantly better mechanical properties and biocompatibility than a single-component hydrogel. This might result from the physical cross-linking and formation of semi-interpenetrating network (semi-IPN). In addition, this novel hydrogel has self-regulate ability to release MNZ in response to the environmental glucose stimulus. Specifically, it released more drugs at higher glucose concentration, thus can lead to a greater ability to inhibit Porphyromonas gingivalis. This study has demonstrated the glucose-sensitive antibacterial hydrogel has a great potential as a new therapeutic material for treatment or prevention of periodontitis in diabetic patients.

Screening the Expression Changes in MicroRNAs and Their Target Genes in Mature Cementoblasts Stimulated with Cyclic Tensile Stress.

Cementum is a thin layer of cementoblast-produced mineralized tissue covering the root surfaces of teeth. Mechanical forces, which are produced during masticatory activity, play a paramount role in stimulating cementoblastogenesis, which thereby facilitates the maintenance, remodeling and integrity of cementum. However, hitherto, the extent to which a post-transcriptional modulation mechanism is involved in this process has rarely been reported. In this study, a mature murine cementoblast cell line OCCM-30 cells (immortalized osteocalcin positive cementoblasts) was cultured and subjected to cyclic tensile stress (0.5 Hz, 2000 µstrain). We showed that the cyclic tensile stress could not only rearrange the cell alignment, but also influence the proliferation in an S-shaped manner. Furthermore, cyclic tensile stress could significantly promote cementoblastogenesis-related genes, proteins and mineralized nodules. From the miRNA array analyses, we found that 60 and 103 miRNAs were significantly altered 6 and 18 h after the stimulation using cyclic tensile stress, respectively. Based on a literature review and bioinformatics analyses, we found that miR-146b-5p and its target gene Smad4 play an important role in this procedure. The upregulation of miR-146b-5p and downregulation of Smad4 induced by the tensile stress were further confirmed by qRT-PCR. The direct binding of miR-146b-5p to the three prime untranslated region (3' UTR) of Smad4 was established using a dual-luciferase reporter assay. Taken together, these results suggest an important involvement of miR-146b-5p and its target gene Smad4 in the cementoblastogenesis of mature cementoblasts.

Delivery of growth factors using a smart porous nanocomposite scaffold to repair a mandibular bone defect.

Implantation of a porous scaffold with a large volume into the body in a convenient and safe manner is still a challenging task in the repair of bone defects. In this study, we present a porous smart nanocomposite scaffold with a combination of shape memory function and controlled delivery of growth factors. The shape memory function enables the scaffold with a large volume to be deformed into its temporal architecture with a small volume using hot-compression and can subsequently recover its original shape upon exposure to body temperature after it is implanted in the body. The scaffold consists of chemically cross-linked poly(ε-caprolactone) (c-PCL) and hydroxyapatite nanoparticles. The highly interconnected pores of the scaffold were obtained using the sugar leaching method. The shape memory porous scaffold loaded with bone morphogenetic protein-2 (BMP-2) was also fabricated by coating the calcium alginate layer and BMP-2 on the surface of the pore wall. Under both in vitro and in vivo environmental conditions, the porous scaffold displays good shape memory recovery from the compressed shape with deformed pores of 33 µm in diameter to recover its porous shape with original pores of 160 µm in diameter. In vitro cytotoxicity based on the MTT test revealed that the scaffold exhibited good cytocompatibility. The in vivo micro-CT and histomorphometry results demonstrated that the porous scaffold could promote new bone generation in the rabbit mandibular bone defect. Thus, our results indicated that this shape memory porous scaffold demonstrated great potential for application in bone regenerative medicine.

25-Hydroxyvitamin D(3)-loaded PLA microspheres: in vitro characterization and application in diabetic periodontitis models.

This study aimed at the preparation of a sustained-release 25-hydroxyvitamin D(3) (25OHD) treatment for diabetic periodontitis, a known complication of diabetes. 25OHD-loaded polylactic acid (PLA) microspheres were prepared using oil-in-water emulsion-solvent evaporation method. The prepared microspheres exhibited intact surfaces, with average sizes ranging from 42.3 to 119.4 µm. The encapsulation efficiency ranged from 79.2% (w/w) to 88.5% (w/w), and the drug content was between 15.8% (w/w) and 17.8% (w/w). Drug release from the produced microspheres followed a near-to-zero-order release pattern and lasted over 10 weeks. In an in vitro model of diabetic periodontitis, the abnormal morphological changes and the decrease in the cell viability of bone marrow stromal cells could be effectively attenuated after the 25OHD-loaded microsphere application. Additionally, in a rat model of diabetic periodontitis, alveolar bone loss was inhibited and osteoid formation in the periodontium was promoted upon 25OHD-loaded microsphere treatment. In conclusion, 25OHD-loaded PLA microspheres may provide an effective approach for the treatment of this disease.

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.

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.

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.

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 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.