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  1. Shariff KA, Tsuru K, Ishikawa K
    Mater Sci Eng C Mater Biol Appl, 2017 Jun 01;75:1411-1419.
    PMID: 28415432 DOI: 10.1016/j.msec.2017.03.004
    β-Tricalcium phosphate (β-TCP) has attracted much attention as an artificial bone substitute owing to its biocompatibility and osteoconductivity. In this study, osteoconductivity of β-TCP bone substitute was enhanced without using growth factors or cells. Dicalcium phosphate dihydrate (DCPD), which is known to possess the highest solubility among calcium phosphates, was coated on β-TCP granules by exposing their surface with acidic calcium phosphate solution. The amount of coated DCPD was regulated by changing the reaction time between β-TCP granules and acidic calcium phosphate solution. Histomorphometry analysis obtained from histological results revealed that the approximately 10mol% DCPD-coated β-TCP granules showed the largest new bone formation compared to DCPD-free β-TCP granules, approximately 2.5mol% DCPD-coated β-TCP granules, or approximately 27mol% DCPD-coated β-TCP granules after 2 and 4weeks of implantation. Based on this finding, we demonstrate that the osteoconductivity of β-TCP granules could be improved by coating their surface with an appropriate amount of DCPD.
    Matched MeSH terms: Bone Regeneration/drug effects*
  2. Kouhi M, Jayarama Reddy V, Fathi M, Shamanian M, Valipouri A, Ramakrishna S
    J Biomed Mater Res A, 2019 06;107(6):1154-1165.
    PMID: 30636094 DOI: 10.1002/jbm.a.36607
    Guided bone regeneration (GBR) has been established to be an effective method for the repair of defective tissues, which is based on isolating bone defects with a barrier membrane for faster tissue reconstruction. The aim of the present study is to develop poly (hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)/fibrinogen (FG)/bredigite (BR) membranes with applicability in GBR. BR nanoparticles were synthesized through a sol-gel method and characterized using transmission electron microscopy and X-ray diffractometer. PHBV, PHBV/FG, and PHBV/FG/BR membranes were fabricated using electrospinning and characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, contact angle, pore size, thermogravimetric analysis and tensile strength. The electrospun PHBV, PHBV/FG, and PHBV/FG/BR nanofibers were successfully obtained with the mean diameter ranging 240-410 nm. The results showed that Young's modulus and ultimate strength of the PHBV membrane reduced upon blending with FG and increased by further incorporation of BR nanoparticles, Moreover hydrophilicity of the PHBV membrane improved on addition of FG and BR. The in vitro degradation assay demonstrated that incorporation of FG and BR into PHBV matrix increased its hydrolytic degradation. Cell-membrane interactions were studied by culturing human fetal osteoblast cells on the fabricated membrane. According to the obtained results, osteoblasts seeded on PHBV/FG/BR displayed higher cell adhesion and proliferation compared to PHBV and PHBV/FG membrane. Furthermore, alkaline phosphatase activity and alizarin red-s staining indicated enhanced osteogenic differentiation and mineralization of cells on PHBV/FG/BR membranes. The results demonstrated that developed electrospun PHBV/FG/BR nanofibrous mats have desired potential as a barrier membrane for guided bone tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1154-1165, 2019.
    Matched MeSH terms: Bone Regeneration/drug effects*
  3. Ginebra MP, Aparicio C, Engel E, Navarro M, Javier Gil F, Planell JA
    Med J Malaysia, 2004 May;59 Suppl B:65-6.
    PMID: 15468821
    Matched MeSH terms: Bone Regeneration/drug effects*
  4. Selvakumar M, Srivastava P, Pawar HS, Francis NK, Das B, Sathishkumar G, et al.
    ACS Appl Mater Interfaces, 2016 Feb 17;8(6):4086-100.
    PMID: 26799576 DOI: 10.1021/acsami.5b11723
    Guided bone regeneration (GBR) scaffolds are futile in many clinical applications due to infection problems. In this work, we fabricated GBR with an anti-infective scaffold by ornamenting 2D single crystalline bismuth-doped nanohydroxyapatite (Bi-nHA) rods onto segmented polyurethane (SPU). Bi-nHA with high aspect ratio was prepared without any templates. Subsequently, it was introduced into an unprecedented synthesized SPU matrix based on dual soft segments (PCL-b-PDMS) of poly(ε-caprolactone) (PCL) and poly(dimethylsiloxane) (PDMS), by an in situ technique followed by electrospinning to fabricate scaffolds. For comparison, undoped pristine nHA rods were also ornamented into it. The enzymatic ring-opening polymerization technique was adapted to synthesize soft segments of PCL-b-PDMS copolymers of SPU. Structure elucidation of the synthesized polymers is done by nuclear magnetic resonance spectroscopy. Sparingly, Bi-nHA ornamented scaffolds exhibit tremendous improvement (155%) in the mechanical properties with excellent antimicrobial activity against various human pathogens. After confirmation of high osteoconductivity, improved biodegradation, and excellent biocompatibility against osteoblast cells (in vitro), the scaffolds were implanted in rabbits by subcutaneous and intraosseous (tibial) sites. Various histological sections reveal the signatures of early cartilage formation, endochondral ossification, and rapid bone healing at 4 weeks of the critical defects filled with ornamented scaffold compared to SPU scaffold. This implies osteogenic potential and ability to provide an adequate biomimetic microenvironment for mineralization for GBR of the scaffolds. Organ toxicity studies further confirm that no tissue architecture abnormalities were observed in hepatic, cardiac, and renal tissue sections. This finding manifests the feasibility of fabricating a mechanically adequate nanofibrous SPU scaffold by a biomimetic strategy and the advantages of Bi-nHA ornamentation in promoting osteoblast phenotype progression with microbial protection (on-demand) for GBR applications.
    Matched MeSH terms: Bone Regeneration/drug effects*
  5. Ngah NA, Ratnayake J, Cooper PR, Dias GJ, Tong DC, Mohd Noor SNF, et al.
    Molecules, 2021 Jan 20;26(3).
    PMID: 33498167 DOI: 10.3390/molecules26030517
    OBJECTIVE: The use of platelet concentrates (PCs) in oral and maxillofacial surgery, periodontology, and craniofacial surgery has been reported. While PCs provide a rich reservoir of autologous bioactive growth factors for tissue regeneration, their drawbacks include lack of utility for long-term application, low elastic modulus and strength, and limited storage capability. These issues restrict their broader application. This review focuses on the lyophilization of PCs (LPCs) and how this processing approach affects their biological and mechanical properties for application as a bioactive scaffold for craniofacial tissue regeneration.

    MATERIALS AND METHODS: A comprehensive search of five electronic databases, including Medline, PubMed, EMBASE, Web of Science, and Scopus, was conducted from 1946 until 2019 using a combination of search terms relating to this topic.

    RESULTS: Ten manuscripts were identified as being relevant. The use of LPCs was mostly studied in in vitro and in vivo craniofacial bone regeneration models. Notably, one clinical study reported the utility of LPCs for guided bone regeneration prior to dental implant placement.

    CONCLUSIONS: Lyophilization can enhance the inherent characteristics of PCs and extends shelf-life, enable their use in emergency surgery, and improve storage and transportation capabilities. In light of this, further preclinical studies and clinical trials are required, as LPCs offer a potential approach for clinical application in craniofacial tissue regeneration.

    Matched MeSH terms: Bone Regeneration/drug effects*
  6. Dong J, Tao L, Abourehab MAS, Hussain Z
    Int J Biol Macromol, 2018 Sep;116:1268-1281.
    PMID: 29782984 DOI: 10.1016/j.ijbiomac.2018.05.116
    Osteoporosis is a medical condition of fragile bones with an increased susceptibility to fracture. Despite having availability of a wide range of pharmacological agents, prevalence of osteoporosis is continuously escalating. Owing to excellent biomedical achievements of nanomedicines in the last few decades, we aimed combo-delivery of bone anti-resorptive agent, alendronate (ALN), and bone density enhancing drug, curcumin (CUR) in the form of polymeric nanoparticles. To further optimize the therapeutic efficacy, the prepared ALN/CUR nanoparticles (NPs) were decorated with hyaluronic acid (HA) which is a well-documented biomacromolecule having exceptional bone regenerating potential. The optimized nanoformulation was then evaluated for bone regeneration efficacy by assessing time-mannered modulation in the proliferation, differentiation, and mineralization of MC3T3-E1 cells, a pre-osteoblastic model. Moreover, the time-mannered expression of various bone-forming protein biomarkers such as bone morphogenetic protein, runt related transcription factor 2, and osteocalcin were assessed in the cell lysates. Results revealed that HA-ALN/CUR NPs provoke remarkable increase in the proliferation, differentiation, and mineralization in the ECM of MC3T3-E1 cells which ultimately leads to enhanced bone formation. This new strategy of employing simultaneous delivery of anti-resorptive and bone forming agents would open new horizons for scientists as an efficient alternative pharmacotherapy for the management of osteoporosis.
    Matched MeSH terms: Bone Regeneration/drug effects*
  7. Shi X, Xu L, Le TB, Zhou G, Zheng C, Tsuru K, et al.
    Mater Sci Eng C Mater Biol Appl, 2016 Feb;59:542-548.
    PMID: 26652406 DOI: 10.1016/j.msec.2015.10.024
    Dental implants made of pure titanium suffer from abrasion and scratch during routine oral hygiene procedures. This results in an irreversible surface damage, facilitates bacteria adhesion and increases risk of peri-implantitis. To overcome these problems, titanium nitride (TiN) coating was introduced to increase surface hardness of pure titanium. However, the osteoconductivity of TiN is considered to be similar or superior to that of titanium and its alloys and therefore surface modification is necessary. In this study, TiN coating prepared through gas nitriding was partially oxidized by hydrothermal (HT) treatment and ozone (O3) treatment in pure water to improve its osteoconductivity. The effects of HT treatment and O3 treatment on surface properties of TiN were investigated and the osteoconductivity after undergoing treatment was assessed in vitro using osteoblast evaluation. The results showed that the critical temperature for HT treatment was 100°C since higher temperatures would impair the hardness of TiN coating. By contrast, O3 treatment was more effective in oxidizing TiN surfaces, improving its wettability while preserving its morphology and hardness. Osteoblast attachment, proliferation, alkaline phosphatase (ALP) expression and mineralization were improved on oxidized specimens, especially on O3 treated specimens, compared with untreated ones. These effects seemed to be consequences of partial oxidation, as well as improved hydrophilicity and surface decontamination. Finally, it was concluded that, partially oxidized TiN is a promising coating to be used for dental implant.
    Matched MeSH terms: Bone Regeneration/drug effects*
  8. Mustafa A, Lung CY, Mustafa NS, Mustafa BA, Kashmoola MA, Zwahlen RA, et al.
    Clin Oral Implants Res, 2016 Mar;27(3):303-9.
    PMID: 25393376 DOI: 10.1111/clr.12525
    OBJECTIVES: To investigate the effect of eicosapentaenoic acid (EPA)-coated Ti implants on osteoconduction in white New Zealand rabbit mandibles.

    MATERIAL AND METHODS: Sandblasted and cleansed planar titanium specimens with a size of 5 × 5 × 1 mm were coated on one side with 0.25 vol% eicosapentaenoic acid (EPA). The other side of the specimens was kept highly polished (the control side). These specimens were inserted in rabbit mandibles. Twelve rabbits were randomly assigned into three study groups (n = 4). The rabbits were sacrificed at 4, 8, and 12 weeks. The harvested specimens with the implants were assessed for new bone formation on both sides of the implant using CBCT, conventional radiographs, and the biaxial pullout test. The results were statistically analyzed by a nonparametric Kruskal-Wallis test and Friedman's test as multiple comparisons and by Brunner-Langer nonparametric mixed model approach (R Software).

    RESULTS: A significant osteoconductive bone formation was found on the EPA-coated Ti implant surface (P < 0.05) at 8 weeks when compared to the polished surface (control). Biaxial pullout test results showed a significant difference (P < 0.05) after 8 and 12 weeks with a maximum force of 243.8 N, compared to 143.25 N after 4 week.

    CONCLUSION: EPA implant coating promoted osteoconduction on the Ti implant surfaces, enhancing the anchorage of the implant to the surrounding bone in white New Zealand rabbits.

    Matched MeSH terms: Bone Regeneration/drug effects*
  9. Hu Y, Ran J, Zheng Z, Jin Z, Chen X, Yin Z, et al.
    Acta Biomater, 2018 04 15;71:168-183.
    PMID: 29524675 DOI: 10.1016/j.actbio.2018.02.019
    Anterior cruciate ligament (ACL) is one of the most difficult tissues to heal once injured. Ligament regeneration and tendon-bone junction healing are two major goals of ACL reconstruction. This study aimed to investigate the synergistic therapeutic effects of Stromal cell-derived factor 1 (SDF-1)-releasing collagen-silk (CSF) scaffold combined with intra-articular injection of ligament-derived stem/progenitor cells (LSPCs) for ACL regeneration and the amelioration in the long-term complication of osteoarthritis (OA). The stem cell recruitment ability of CSF scaffold and the multipotency, particularly the tendon forming ability of LSPCs from rabbits were characterized in vitro, while the synergistic effect of the CSF scaffold and LSPCs for ACL regeneration and OA amelioration were investigated in vivo at 1, 3, and 6 months with a rabbit ACL reconstruction model. The CSF scaffold was used as a substitute for the ACL, and LSPCs were injected into the joint cavity after 7 days of the ACL reconstruction. CSF scaffold displayed a controlled release pattern for the encapsulated protein for up to 7 days with an increased stiffness in the mechanical property. LSPCs, which exhibited highly I Collagen and CXCR4 expression, were attracted by SDF-1 and successfully relocated into the CSF scaffold at 1 month in vivo. At 3 and 6 months post-treatment, the CSF scaffold combined with LSPCs (CSFL group) enhanced the regeneration of ACL tissue, and promoted bone tunnel healing. Furthermore, the OA progression was impeded efficiently. Our findings here provided a new strategy that using stem cell recruiting CSF scaffold with tissue-specific stem cells, could be a promising solution for ACL regeneration.

    STATEMENT OF SIGNIFICANCE: In this study, we developed a silk scaffold with increased stiffness and SDF-1 controlled release capacity for ligament repair. This advanced scaffold transplantation combined with intra-articular injection of LSPCs (which was isolated from rabbit ligament for the first time in this study) promoted the regeneration of both the tendinous and bone tunnel portion of ACL. This therapeutic strategy also ameliorated cartilage degeneration and reduced the severity of arthrofibrosis. Hence, combining LSPCs injection with SDF-1-releasing silk scaffold is demonstrated as a therapeutic strategy for ACL regeneration and OA treatment in the clinic.

    Matched MeSH terms: Bone Regeneration/drug effects*
  10. Ngah NA, Dias GJ, Tong DC, Mohd Noor SNF, Ratnayake J, Cooper PR, et al.
    Molecules, 2021 Nov 25;26(23).
    PMID: 34885714 DOI: 10.3390/molecules26237131
    BACKGROUND: Platelet-rich fibrin (PRF) has gained popularity in craniofacial surgery, as it provides an excellent reservoir of autologous growth factors (GFs) that are essential for bone regeneration. However, the low elastic modulus, short-term clinical application, poor storage potential and limitations in emergency therapy use restrict its more widespread clinical application. This study fabricates lyophilised PRF (Ly-PRF), evaluates its physical and biological properties, and explores its application for craniofacial tissue engineering purposes.

    MATERIAL AND METHODS: A lyophilisation method was applied, and the outcome was evaluated and compared with traditionally prepared PRF. We investigated how lyophilisation affected PRF's physical characteristics and biological properties by determining: (1) the physical and morphological architecture of Ly-PRF using SEM, and (2) the kinetic release of PDGF-AB using ELISA.

    RESULTS: Ly-PRF exhibited a dense and homogeneous interconnected 3D fibrin network. Moreover, clusters of morphologically consistent cells of platelets and leukocytes were apparent within Ly-PRF, along with evidence of PDGF-AB release in accordance with previously reports.

    CONCLUSIONS: The protocol established in this study for Ly-PRF preparation demonstrated versatility, and provides a biomaterial with growth factor release for potential use as a craniofacial bioscaffold.

    Matched MeSH terms: Bone Regeneration/drug effects
  11. Iqbal B, Sarfaraz Z, Muhammad N, Ahmad P, Iqbal J, Khan ZUH, et al.
    J Biomater Sci Polym Ed, 2018 07;29(10):1168-1184.
    PMID: 29460709 DOI: 10.1080/09205063.2018.1443604
    In this study, collagen/alginate/hydroxyapatite beads having different proportions were prepared as bone fillers for the restoration of osteological defects. Ionic liquid was used to dissolve the collagen and subsequently the solution was mixed with sodium alginate solution. Hydroxyapatite was added in different proportions, with the rationale to enhance mechanical as well as biological properties. The prepared solutions were given characteristic bead shapes by dropwise addition into calcium chloride solution. The prepared beads were characterized using FTIR, XRD, TGA and SEM analysis. Microhardness testing was used to evaluate the mechanical properties. The prepared beads were investigated for water adsorption behavior to ascertain its ability for body fluid uptake and adjusted accordingly to the bone cavity. Drug loading and subsequently the antibacterial activity was investigated for the prepared beads. The biocompatibility was assessed using the hemolysis testing and cell proliferation assay. The prepared collagen-alginate-HA beads, having biocompatibility and good mechanical properties, have showed an option of promising biologically active bone fillers for bone regeneration.
    Matched MeSH terms: Bone Regeneration/drug effects*
  12. Amin Yavari S, van der Stok J, Chai YC, Wauthle R, Tahmasebi Birgani Z, Habibovic P, et al.
    Biomaterials, 2014 Aug;35(24):6172-81.
    PMID: 24811260 DOI: 10.1016/j.biomaterials.2014.04.054
    The large surface area of highly porous titanium structures produced by additive manufacturing can be modified using biofunctionalizing surface treatments to improve the bone regeneration performance of these otherwise bioinert biomaterials. In this longitudinal study, we applied and compared three types of biofunctionalizing surface treatments, namely acid-alkali (AcAl), alkali-acid-heat treatment (AlAcH), and anodizing-heat treatment (AnH). The effects of treatments on apatite forming ability, cell attachment, cell proliferation, osteogenic gene expression, bone regeneration, biomechanical stability, and bone-biomaterial contact were evaluated using apatite forming ability test, cell culture assays, and animal experiments. It was found that AcAl and AnH work through completely different routes. While AcAl improved the apatite forming ability of as-manufactured (AsM) specimens, it did not have any positive effect on cell attachment, cell proliferation, and osteogenic gene expression. In contrast, AnH did not improve the apatite forming ability of AsM specimens but showed significantly better cell attachment, cell proliferation, and expression of osteogenic markers. The performance of AlAcH in terms of apatite forming ability and cell response was in between both extremes of AnH and AsM. AcAl resulted in significantly larger volumes of newly formed bone within the pores of the scaffold as compared to AnH. Interestingly, larger volumes of regenerated bone did not translate into improved biomechanical stability as AnH exhibited significantly better biomechanical stability as compared to AcAl suggesting that the beneficial effects of cell-nanotopography modulations somehow surpassed the benefits of improved apatite forming ability. In conclusion, the applied surface treatments have considerable effects on apatite forming ability, cell attachment, cell proliferation, and bone ingrowth of the studied biomaterials. The relationship between these properties and the bone-implant biomechanics is, however, not trivial.
    Matched MeSH terms: Bone Regeneration/drug effects*
  13. Shalan NA, Mustapha NM, Mohamed S
    Nutrition, 2017 Jan;33:42-51.
    PMID: 27908549 DOI: 10.1016/j.nut.2016.08.006
    OBJECTIVE: Black tea and Nonileaf are among the dietary compounds that can benefit patients with bone resorption disorders. Their bone regeneration effects and their mechanisms were studied in estrogen-deficient rats.

    METHODS: Noni leaves (three doses) and black tea water extracts were fed to ovariectomized rats for 4 mo, and their effects (analyzed via mechanical measurements, micro-computed tomography scan, and reverse transcriptase polymerase chain reaction mRNA) were compared with Remifemin (a commercial phytoestrogen product from black cohosh).

    RESULTS: The water extracts (dose-dependently for noni leaves) increased bone regeneration biomarker (runt-related transcription factor 2, bone morphogenetic protein 2, osteoprotegerin, estrogen receptor 1 [ESR1], collagen type I alpha 1A) expressions and reduced the inflammatory biomarkers (interleukin-6, tumor necrosis factor-α, nuclear factor [NF]-κB, and receptor activator of NF-κB ligand) mRNA expressions/levels in the rats. The extracts also improved bone physical and mechanical properties. The extracts demonstrated bone regeneration through improving bone size and structure, bone mechanical properties (strength and flexibility), and bone mineralization and density.

    CONCLUSIONS: The catechin-rich extract favored bone regeneration and suppressed bone resorption. The mechanisms involved enhancing osteoblast generation and survival, inhibiting osteoclast growth and activities, suppressing inflammation, improving bone collagen synthesis and upregulating ESR1 expression to augment phytoestrogenic effects. Estrogen deficiency bone loss and all extracts studied (best effect from Morinda leaf at 300 mg/kg body weight) mitigated the loss, indicating benefits for the aged and menopausal women.

    Matched MeSH terms: Bone Regeneration/drug effects*
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