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Bioactive glass reinforced elastomer composites for skeletal regeneration: A review

Zeimaran E, Pourshahrestani S, Djordjevic I, Pingguan-Murphy B, Kadri NA, Towler MR

Mater Sci Eng C Mater Biol Appl, 2015 Aug;53:175-88.
PMID: 26042705 DOI: 10.1016/j.msec.2015.04.035

Biodegradable elastomers have clinical applicability due to their biocompatibility, tunable degradation and elasticity. The addition of bioactive glasses to these elastomers can impart mechanical properties sufficient for hard tissue replacement. Hence, a composite with a biodegradable polymer matrix and a bioglass filler can offer a method of augmenting existing tissue. This article reviews the applications of such composites for skeletal augmentation.

Matched MeSH terms: Bone Regeneration*
Nanophase hydroxyapatite as a biomaterial in advanced hard tissue engineering: a review

Zakaria SM, Sharif Zein SH, Othman MR, Yang F, Jansen JA

Tissue Eng Part B Rev, 2013 Oct;19(5):431-41.
PMID: 23557483 DOI: 10.1089/ten.TEB.2012.0624

Hydroxyapatite is a biocompatible material that is extensively used in the replacement and regeneration of bone material. In nature, nanostructured hydroxyapatite is the main component present in hard body tissues. Hence, the state of the art in nanotechnology can be exploited to synthesize nanophase hydroxyapatite that has similar properties with natural hydroxyapatite. Sustainable methods to mass-produce synthetic hydroxyapatite nanoparticles are being developed to meet the increasing demand for these materials and to further develop the progress made in hard tissue regeneration, especially for orthopedic and dental applications. This article reviews the current developments in nanophase hydroxyapatite through various manufacturing techniques and modifications.

Matched MeSH terms: Bone Regeneration*
Evaluation of bone healing following immediate and delayed dental implant placement

Younis L, Taher A, Abu-Hassan MI, Tin O

J Contemp Dent Pract, 2009;10(4):35-42.
PMID: 19575052

The purpose of this study was to compare bone healing and coronal bone remodeling following both immediate and delayed placement of titanium dental implants in extraction sockets.

Matched MeSH terms: Bone Regeneration*
Tissue-engineered bone applied for alveolar ridge augmentation with simultaneous implant

Ueda M

Med J Malaysia, 2004 May;59 Suppl B:29.
PMID: 15468803
Matched MeSH terms: Bone Regeneration/physiology
Efficacy and bone-contact biocompatibility of glass ionomer cement as a biomaterial for bone regeneration: A systematic review

Tuygunov N, Zakaria MN, Yahya NA, Abdul Aziz A, Cahyanto A

J Mech Behav Biomed Mater, 2023 Oct;146:106099.
PMID: 37660446 DOI: 10.1016/j.jmbbm.2023.106099

Bone regeneration is a rapidly growing field that seeks to develop new biomaterials to regenerate bone defects. Conventional bone graft materials have limitations, such as limited availability, complication, and rejection. Glass ionomer cement (GIC) is a biomaterial with the potential for bone regeneration due to its bone-contact biocompatibility, ease of use, and cost-effectiveness. GIC is a two-component material that adheres to the bone and releases ions that promote bone growth and mineralization. A systematic literature search was conducted using PubMed-MEDLINE, Scopus, and Web of Science databases and registered in the PROSPERO database to determine the evidence regarding the efficacy and bone-contact biocompatibility of GIC as bone cement. Out of 3715 initial results, thirteen studies were included in the qualitative synthesis. Two tools were employed in evaluating the Risk of Bias (RoB): the QUIN tool for assessing in vitro studies and SYRCLE for in vivo. The results indicate that GIC has demonstrated the ability to adhere to bone and promote bone growth. Establishing a chemical bond occurs at the interface between the GIC and the mineral phase of bone. This interaction allows the GIC to exhibit osteoconductive properties and promote the growth of bone tissue. GIC's bone-contact biocompatibility, ease of preparation, and cost-effectiveness make it a promising alternative to conventional bone grafts. However, further research is required to fully evaluate the potential application of GIC in bone regeneration. The findings hold implications for advancing material development in identifying the optimal composition and fabrication of GIC as a bone repair material.

Matched MeSH terms: Bone Regeneration
Oxygen-Releasing Scaffolds for Accelerated Bone Regeneration

Touri M, Moztarzadeh F, Abu Osman NA, Dehghan MM, Brouki Milan P, Farzad-Mohajeri S, et al.

ACS Biomater Sci Eng, 2020 05 11;6(5):2985-2994.
PMID: 33463293 DOI: 10.1021/acsbiomaterials.9b01789

Hypoxia, the result of disrupted vasculature, can be categorized in the main limiting factors for fracture healing. A lack of oxygen can cause cell apoptosis, tissue necrosis, and late tissue healing. Remedying hypoxia by supplying additional oxygen will majorly accelerate bone healing. In this study, biphasic calcium phosphate (BCP) scaffolds were fabricated by robocasting, an additive manufacturing technique. Then, calcium peroxide (CPO) particles, as an oxygen-releasing agent, were coated on the BCP scaffolds. Segmental radial defects with the size of 15 mm were created in rabbits. Uncoated and CPO-coated BCP scaffolds were implanted in the defects. The empty (control) group received no implantation. Repairing of the bone was investigated via X-ray, histological analysis, and biomechanical tests at 3 and 6 months postoperatively, with immunohistochemical examinations at 6 months after operation. According to the radiological observations, formation of new bone was augmented at the interface between the implant and host bone and internal pores of CPO-coated BCP scaffolds compared to uncoated scaffolds. Histomorphometry analysis represented that the amount of newly formed bone in the CPO-coated scaffold was nearly two times higher than the uncoated one. Immunofluorescence staining revealed that osteogenic markers, osteonectin and octeocalcin, were overexpressed in the defects treated with the coated scaffolds at 6 months of postsurgery, demonstrating higher osteogenic differentiation and bone mineralization compared to the uncoated scaffold group. Furthermore, the coated scaffolds had superior biomechanical properties as in the case of 3 months after surgery, the maximal flexural force of the coated scaffolds reached to 134 N, while it was 92 N for uncoated scaffolds. The results could assure a boosted ability of bone repair for CPO-coated BCP scaffolds implanted in the segmental defect of rabbit radius because of oxygen-releasing coating, and this system of oxygen-generating coating/scaffold might be a potential for accelerated repairing of bone defects.

Matched MeSH terms: Bone Regeneration
Strategy for generating tissue-engineered human bone construct

Tan KK, Aminuddin BS, Tan GH, Sabarul Afian M, Ng MH, Fauziah O, et al.

Med J Malaysia, 2004 May;59 Suppl B:43-4.
PMID: 15468810

The strategy used to generate tissue-engineered bone construct, in view of future clinical application is presented here. Osteoprogenitor cells from periosteum of consenting scoliosis patients were isolated. Growth factors viz TGF-B2, bFGF and IGF-1 were used in concert to increase cell proliferation during in vitro cell expansion. Porous tricalcium phosphate (TCP)-hydroxyapatite (HA) scaffold was used as the scaffold to form 3D bone construct. We found that the addition of growth factors, greatly increased cell growth by 2 to 7 fold. TCP/HA proved to be the ideal scaffold for cell attachment and proliferation. Hence, this model will be further carried out on animal trial.

Matched MeSH terms: Bone Regeneration/physiology*
Fracture Non-Union: A Review of Clinical Challenges and Future Research Needs

Stewart SK

Malays Orthop J, 2019 Jul;13(2):1-10.
PMID: 31467644 DOI: 10.5704/MOJ.1907.001

Non-union of bone following fracture is an orthopaedic condition with a high morbidity and clinical burden. Despite its estimated global prevalence of nine million annually, the limit of bone regeneration therapy still results in patients living with pain, a reduced quality of life and associated psychological, social and financial repercussions. This review provides an overview of the current epidemiological and aetiological data, and highlights where the clinical challenges in treating non-union lie. Current treatment strategies are discussed as well as promising future research foci. Development in biotechnologies to treat non-union provides exciting scope for more effective treatment for this debilitating condition.

Matched MeSH terms: Bone Regeneration
Recent development on porous calcium phosphate ceramics for biomedical application

Sopyan I

Med J Malaysia, 2008 Jul;63 Suppl A:14-5.
PMID: 19024961

Porous calcium phosphate ceramics have found enormous use in biomedical applications including bone tissue regeneration, cell proliferation, and drug delivery. In bone tissue engineering it has been applied as filling material for bone defects and augmentation, artificial bone graft material, and prosthesis revision surgery. Their high surface area leads to excellent osteoconductivity and resorbability providing fast bone ingrowths. Porous calcium phosphate can be produced by a variety of methods. This paper discusses briefly fundamental aspects of porous calcium phosphate for biomedical applications as well as various techniques used to prepare porous calcium phosphate.

Matched MeSH terms: Bone Regeneration
Partial oxidation of TiN coating by hydrothermal treatment and ozone treatment to improve its osteoconductivity

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*
Fabrication of dicalcium phosphate dihydrate-coated β-TCP granules and evaluation of their osteoconductivity using experimental rats

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*
Noni leaf and black tea enhance bone regeneration in estrogen-deficient rats

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*
On-Demand Guided Bone Regeneration with Microbial Protection of Ornamented SPU Scaffold with Bismuth-Doped Single Crystalline Hydroxyapatite: Augmentation and Cartilage Formation

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*
Fulltext Massive Tibial Bone Regeneration with Autologous Peripheral Blood Stem Cells using Ilizarov Bone Transport: A Case Report

Saw KY, Gill R, Low TC

Malays Orthop J, 2020 Nov;14(3):166-169.
PMID: 33403079 DOI: 10.5704/MOJ.2011.026

This is a case report of a Gustilo-Anderson Type IIIB comminuted open right tibial fracture with massive bone loss, complicated by methicillin-resistant Staphylococus aureus (MRSA) infection. Non-viable and contaminated bony fragments were removed and infected bone resected. Soft tissue coverage and antibiotics were effective against the MRSA infection. A unifocal bone transport with the Ilizarov method regenerated 13cm of the missing tibia. Autologous peripheral blood stem cells (PBSC) injections into the osteogenesis site boosted bone regeneration and consolidation with a shortened Bone Healing index (BHI) of 23 days/cm.

Matched MeSH terms: Bone Regeneration
Efficacy of guided bone regeneration using composite bone graft and resorbable collagen membrane in Seibert's Class I ridge defects: radiological evaluation

Saravanan P, Ramakrishnan T, Ambalavanan N, Emmadi P, John TL

J Oral Implantol, 2013 Aug;39(4):455-62.
PMID: 23964779 DOI: 10.1563/AAID-JOI-D-10-00211

The purpose of the study was to evaluate radiologically the efficacy of guided bone regeneration using composite bone graft (autogenous bone graft and anorganic bovine bone graft [Bio-Oss]) along with resorbable collagen membrane (BioMend Extend) in the augmentation of Seibert's class I ridge defects in maxilla. Bone width was evaluated using computerized tomography at day 0 and at day 180 at 2 mm, 4 mm, and 6 mm from the crest. There was a statistically significant increase in bone width between day 0 and day 180 at 2 mm, 4 mm, and 6 mm from the crest. The results of the study demonstrated an increase in bone width of Seibert's class I ridge defects in the maxilla of the study patients.

Matched MeSH terms: Bone Regeneration*
Bone biology in craniofacial growth, development and ageing

Samsudin AR

Med J Malaysia, 2004 May;59 Suppl B:6.
PMID: 15468791
Matched MeSH terms: Bone Regeneration/physiology
Fulltext Antibacterial efficacy of triple-layered poly(lactic-co-glycolic acid)/nanoapatite/lauric acid guided bone regeneration membrane on periodontal bacteria

Saarani NN, Jamuna-Thevi K, Shahab N, Hermawan H, Saidin S

Dent Mater J, 2017 May 31;36(3):260-265.
PMID: 28111388 DOI: 10.4012/dmj.2016-177

A guided bone regeneration (GBR) membrane has been extensively used in the repair and regeneration of damaged periodontal tissues. One of the main challenges of GBR restoration is bacterial colonization on the membrane, constitutes to premature membrane degradation. Therefore, the purpose of this study was to investigate the antibacterial efficacy of triple-layered GBR membrane composed of poly(lactic-co-glycolic acid) (PLGA), nanoapatite (NAp) and lauric acid (LA) with two types of Gram-negative periodontal bacteria, Fusobacterium nucleatum and Porphyromonas gingivalis through a disc diffusion and bacterial count tests. The membranes exhibited a pattern of growth inhibition and killing effect against both bacteria. The increase in LA concentration tended to increase the bactericidal activities which indicated by higher diameter of inhibition zone and higher antibacterial percentage. It is shown that the incorporation of LA into the GBR membrane has retarded the growth and proliferation of Gram-negative periodontal bacteria for the treatment of periodontal disease.

Matched MeSH terms: Bone Regeneration*
Bioglass® 45S5-based composites for bone tissue engineering and functional applications

Rizwan M, Hamdi M, Basirun WJ

J Biomed Mater Res A, 2017 Nov;105(11):3197-3223.
PMID: 28686004 DOI: 10.1002/jbm.a.36156

Bioglass® 45S5 (BG) has an outstanding ability to bond with bones and soft tissues, but its application as a load-bearing scaffold material is restricted due to its inherent brittleness. BG-based composites combine the amazing biological and bioactive characteristics of BG with structural and functional features of other materials. This article reviews the composites of Bioglass® in combination with metals, ceramics and polymers for a wide range of potential applications from bone scaffolds to nerve regeneration. Bioglass® also possesses angiogenic and antibacterial properties in addition to its very high bioactivity; hence, composite materials developed for these applications are also discussed. BG-based composites with polymer matrices have been developed for a wide variety of soft tissue engineering. This review focuses on the research that suggests the suitability of BG-based composites as a scaffold material for hard and soft tissues engineering. Composite production techniques have a direct influence on the bioactivity and mechanical behavior of scaffolds. A detailed discussion of the bioactivity, in vitro and in vivo biocompatibility and biodegradation is presented as a function of materials and its processing techniques. Finally, an outlook for future research is also proposed. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3197-3223, 2017.

Matched MeSH terms: Bone Regeneration
Fulltext The immunologic properties of undifferentiated stem cells from human exfoliated deciduous teeth (SHED) and its potential application in bone regeneration

Nurul, A.A., Tan, S.J., Asiah, A.B., Norliana, G., Nor Shamsuria, O., Nurul, A.S.

International Medical Journal Malaysia, 2013;12(1):19-26.
MyJurnal

Introduction: Stem cells from human exfoliated deciduous teeth (SHED) are highly proliferative, clonogenic cells capable of differentiating into osteoblasts and inducing bone formation. It is a potential alternative for stem cell bone regeneration therapy. However, stem cell therapy carries the risk of immune rejection mediated by inflammatory cytokines of the human defense system. Objective: This preliminary research studies the interaction between SHED and the immune system by determining the inflammatory cytokines profile and osteogenic potential of SHED. Methods: Human fetal osteoblasts (hFOb) cell line and isolated SHED were cultured and total RNA was extracted, followed by reverse transcription cDNA synthesis. Semi-quantitative reverse transcription PCR and Multiplex PCR were performed to detect the expression levels of OPG/RANKL and TNF-α, IL-1β, IL-6, IL-8 and TGF-β in both cell types. Results: Analysis showed that SHED expressed significantly lower amounts of IL-1β, IL-6, and IL-8 compared to hFOB. IL-1β is a potent bone-resorbing factor, while IL-6 and IL-8 induce osteoclastogenesis and osteolysis respectively. SHED did not express TNF-α which stimulates osteoclastic activity. SHED demonstrated high OPG/RANKL ratio, in contrast with that of marrow stem cells described in previous studies. Our findings suggest that SHED may have improved immunomodulatory profile in terms of promoting relatively lower inflammatory reaction during transplant and enhancing bone regeneration. Conclusion: SHED has a potential to be a good source of osteoblasts for bone regeneration therapy. Further studies on the immunomodulatory properties of SHED-derived osteoblasts are necessary to enable stem cell therapy in immunocompetent hosts.

Matched MeSH terms: Bone Regeneration
Fulltext Potential of Lyophilized Platelet Concentrates for Craniofacial Tissue Regenerative Therapies

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*

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