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Advanced Drug Delivery Reviews Aug 2023Unlike orthopedic implants, dental implants require the orchestration of both osseointegration at the bone-implant interface and soft-tissue integration at the... (Review)
Review
Unlike orthopedic implants, dental implants require the orchestration of both osseointegration at the bone-implant interface and soft-tissue integration at the transmucosal region in a complex oral micro-environment with ubiquitous pathogenic bacteria. This represents a very challenging environment for early acceptance and long-term survival of dental implants, especially in compromised patient conditions, including aged, smoking and diabetic patients. Enabling advanced local therapy from the surface of titanium-based dental implants via novel nano-engineering strategies is emerging. This includes anodized nano-engineered implants eluting growth factors, antibiotics, therapeutic nanoparticles and biopolymers to achieve maximum localized therapeutic action. An important criterion is balancing bioactivity enhancement and therapy (like bactericidal efficacy) without causing cytotoxicity. Critical research gaps still need to be addressed to enable the clinical translation of these therapeutic dental implants. This review informs the latest developments, challenges and future directions in this domain to enable the successful fabrication of clinically-translatable therapeutic dental implants that would allow for long-term success, even in compromised patient conditions.
Topics: Humans; Aged; Dental Implants; Nanotechnology; Osseointegration; Bacteria; Dental Implantation; Titanium; Surface Properties
PubMed: 37263543
DOI: 10.1016/j.addr.2023.114900 -
Injury Nov 2022Since ancient times, reduction and internal fixation has been applied to restore skeletal integrity. Despite advances in the understanding of fracture healing, the risk... (Review)
Review
Since ancient times, reduction and internal fixation has been applied to restore skeletal integrity. Despite advances in the understanding of fracture healing, the risk of complication such as implant loosening or implant-related infection still depicts a challenging complication. Nowadays, a great deal of research is devoted to unreveal the impact of implant surface modifications on osteogenic processes to enhance bone consolidation and osseointegration. This narrative review is aimed to (1) show the evolution and already achieved milestones of implant optimization, and (2) to outline the key factors that contribute to an enhanced osseointegration. Different physical and chemical roughening techniques are currently applied in various studies. Surface patterning on the nanoscale has been found to be an essential factor for the biological response, achievable by e.g. anodisation or laser texturing. Besides surface roughening, also different coating methods are vastly investigated. Next to metal or inorganic compounds as coating material, a variety of biomolecules is currently studied for their osteosupportive capacities. Osseointegration can be improved by surface modification on the micro and nanoscale. Bioactive agents can further improve the osseointegration potential. Used agents at the moment are e.g. inorganic compounds, growth factors (BMPs and non-BMPs) and antiresorptive drugs. The advancement in research on new implant generations therefore aims at actively supporting osseointegration processing.
Topics: Bone Density Conservation Agents; Coated Materials, Biocompatible; Humans; Osseointegration; Osteogenesis; Prostheses and Implants; Surface Properties; Titanium
PubMed: 35948509
DOI: 10.1016/j.injury.2022.05.057 -
Archives of Biochemistry and Biophysics Oct 2020The main component of plasma medicine is the use of low-temperature plasma (LTP) as a powerful tool for biomedical applications. LTP generates high reactivity at low... (Review)
Review
The main component of plasma medicine is the use of low-temperature plasma (LTP) as a powerful tool for biomedical applications. LTP generates high reactivity at low temperatures and can be activated with noble gases with molecular mixtures or compressed air. LTP reactive species are quickly produced, and are a remarkably good source of reactive oxygen and nitrogen species including singlet oxygen (O), ozone (O), hydroxyl radicals (OH), nitrous oxide (NO), and nitrogen dioxide (NO). Its low gas temperature and highly reactive non-equilibrium chemistry make it appropriate for the alteration of inorganic surfaces and delicate biological systems. Treatment of oral biofilm-related infections, treatment of wounds and skin diseases, assistance in cancer treatment, treatment of viruses' infections (e.g. herpes simplex), and optimization of implants surfaces are included among the extensive plasma medicine applications. Each of these applications will be discussed in this review article.
Topics: Anti-Infective Agents; Antineoplastic Agents; Cold Temperature; Dental Implants; Humans; Osseointegration; Plasma Gases; Viral Load; Wound Healing
PubMed: 32857998
DOI: 10.1016/j.abb.2020.108560 -
Sensors (Basel, Switzerland) Sep 2022Osseointegration implant has attracted significant attention as an alternative treatment for transfemoral amputees. It has been shown to improve patients' sitting and...
Osseointegration implant has attracted significant attention as an alternative treatment for transfemoral amputees. It has been shown to improve patients' sitting and walking comfort and control of the artificial limb, compared to the conventional socket device. However, the patients treated with osseointegration implants require a long rehabilitation period to establish sufficient femur-implant connection, allowing the full body weight on the prosthesis stem. Hence, a robust assessment method on the osseointegration process is essential to shorten the rehabilitation period and identify the degree of osseointegration prior to the connection of an artificial limb. This paper investigates the capability of a vibration-related index (E-index) on detecting the degree of simulated osseointegration process with three lengths of the residual femur (152, 190 and 228 mm). The adhesive epoxy with a setting time of 5 min was applied at the femur-implant interface to represent the stiffness change during the osseointegration process. The cross-spectrum and colormap of the normalised magnitude demonstrated significant changes during the cure time, showing that application of these plots could improve the accuracy of the currently available diagnostic techniques. Furthermore, the E-index exhibited a clear trend with a noticeable average increase of 53% against the cure time for all three residual length conditions. These findings highlight that the E-index can be employed as a quantitative justification to assess the degree of osseointegration process without selecting and tracing the resonant frequency based on the geometry of the residual femur.
Topics: Amputees; Artificial Limbs; Femur; Humans; Osseointegration; Prosthesis Implantation; Vibration
PubMed: 36146079
DOI: 10.3390/s22186727 -
Journal of Neuroengineering and... Mar 2022Electrical stimulation has shown to be a promising approach for promoting osseointegration in bone anchoring implants, where osseointegration defines the biological... (Review)
Review
Electrical stimulation has shown to be a promising approach for promoting osseointegration in bone anchoring implants, where osseointegration defines the biological bonding between the implant surface and bone tissue. Bone-anchored implants are used in the rehabilitation of hearing and limb loss, and extensively in edentulous patients. Inadequate osseointegration is one of the major factors of implant failure that could be prevented by accelerating or enhancing the osseointegration process by artificial means. In this article, we reviewed the efforts to enhance the biofunctionality at the bone-implant interface with electrical stimulation using the implant as an electrode. We reviewed articles describing different electrode configurations, power sources, and waveform-dependent stimulation parameters tested in various in vitro and in vivo models. In total 55 English-language and peer-reviewed publications were identified until April 2020 using PubMed, Google Scholar, and the Chalmers University of Technology Library discovery system using the keywords: osseointegration, electrical stimulation, direct current and titanium implant. Thirteen of those publications were within the scope of this review. We reviewed and compared studies from the last 45 years and found nonuniform protocols with disparities in cell type and animal model, implant location, experimental timeline, implant material, evaluation assays, and type of electrical stimulation. The reporting of stimulation parameters was also found to be inconsistent and incomplete throughout the literature. Studies using in vitro models showed that osteoblasts were sensitive to the magnitude of the electric field and duration of exposure, and such variables similarly affected bone quantity around implants in in vivo investigations. Most studies showed benefits of electrical stimulation in the underlying processes leading to osseointegration, and therefore we found the idea of promoting osseointegration by using electric fields to be supported by the available evidence. However, such an effect has not been demonstrated conclusively nor optimally in humans. We found that optimal stimulation parameters have not been thoroughly investigated and this remains an important step towards the clinical translation of this concept. In addition, there is a need for reporting standards to enable meta-analysis for evidence-based treatments.
Topics: Animals; Bone-Implant Interface; Electric Stimulation; Humans; Osseointegration; Prostheses and Implants; Surface Properties; Titanium
PubMed: 35313892
DOI: 10.1186/s12984-022-01005-7 -
Periodontology 2000 Oct 2022Historically, there has been broad consensus that osseointegration represents a homeostasis between a titanium dental implant and the surrounding bone, and that the... (Review)
Review
Historically, there has been broad consensus that osseointegration represents a homeostasis between a titanium dental implant and the surrounding bone, and that the crestal bone loss characteristic of peri-implantitis is a plaque-induced inflammatory process. However, this notion has been challenged over the past decade by proponents of a theory that considers osseointegration an inflammatory process characterized by a foreign body reaction and peri-implant bone loss as an exacerbation of this inflammatory response. A key difference in these two schools of thought is the perception of the relative importance of dental plaque in the pathogenesis of crestal bone loss around implants, with obvious implications for treatment. This review investigates the evidence for a persistent foreign body reaction at osseointegrated dental implants and its possible role in crestal bone loss characteristic of peri-implantitis. Further, the role of implant-related material release within the surrounding tissue, particularly titanium particles and corrosion by-products, in the establishment and progression in peri-implantitis is explored. While it is acknowledged that these issues require further investigation, the available evidence suggests that osseointegration is a state of homeostasis between the titanium implant and surrounding tissues, with little evidence that a persistent foreign body reaction is responsible for peri-implant bone loss after osseointegration is established. Further, there is a lack of evidence for a unidirectional causative role of corrosion by-products and titanium particles as possible non-plaque related factors in the etiology of peri-implantitis.
Topics: Alveolar Bone Loss; Dental Implants; Foreign Bodies; Foreign-Body Reaction; Humans; Osseointegration; Peri-Implantitis; Titanium
PubMed: 35916872
DOI: 10.1111/prd.12456 -
International Journal of Oral Science Jan 2024Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues. Magnesium has been proved to promote bone...
Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues. Magnesium has been proved to promote bone healing under normal conditions. Here, we elucidate the mechanism by which Mg promotes angiogenesis and osseointegration in diabetic status. We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised, with significantly decreased angiogenesis. We then developed Mg-coating implants with hydrothermal synthesis. These implants successfully improved the vascularization and osseointegration in diabetic status. Mechanically, Mg promoted the degradation of Kelch-like ECH-associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells, thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia. Altogether, our data suggested that Mg promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.
Topics: Mice; Animals; Kelch-Like ECH-Associated Protein 1; Magnesium; Osseointegration; Diabetes Mellitus, Experimental; Endothelial Cells; NF-E2-Related Factor 2
PubMed: 38296940
DOI: 10.1038/s41368-023-00271-y -
Molecules (Basel, Switzerland) Dec 2020The contribution of epigenetic mechanisms as a potential treatment model has been observed in cancer and autoimmune/inflammatory diseases. This review aims to put... (Review)
Review
The contribution of epigenetic mechanisms as a potential treatment model has been observed in cancer and autoimmune/inflammatory diseases. This review aims to put forward the epigenetic mechanisms as a promising strategy in implant surface functionalization and modification of biomaterials, to promote better osseointegration and bone regeneration, and could be applicable for alveolar bone regeneration and osseointegration in the future. Materials and Methods: Electronic and manual searches of the literature in PubMed, MEDLINE, and EMBASE were conducted, using a specific search strategy limited to publications in the last 5 years to identify preclinical studies in order to address the following focused questions: (i) Which, if any, are the epigenetic mechanisms used to functionalize implant surfaces to achieve better osseointegration? (ii) Which, if any, are the epigenetic mechanisms used to functionalize biomaterials to achieve better tissue regeneration? Findings from several studies have emphasized the role of miRNAs in functionalizing implants surfaces and biomaterials to promote osseointegration and bone regeneration, respectively. However, there are scarce data on the role of DNA methylation and histone modifications for these specific applications, despite being commonly applied in cancer research. Studies over the past few years have demonstrated that biomaterials are immunomodulatory rather than inert materials. In this context, epigenetics can act as next generation of advanced treatment tools for future regenerative techniques. Yet, there is a need to evaluate the efficacy/cost effectiveness of these techniques in comparison to current standards of care.
Topics: Animals; Biocompatible Materials; Bone Regeneration; Epigenesis, Genetic; Humans; Osseointegration
PubMed: 33322654
DOI: 10.3390/molecules25245879 -
European Review For Medical and... Jun 2023Recently, nutraceuticals have been widely explored in many medical fields and their use is also increasing in oral and dental problems. Since the nutraceutical evidence... (Review)
Review
OBJECTIVE
Recently, nutraceuticals have been widely explored in many medical fields and their use is also increasing in oral and dental problems. Since the nutraceutical evidence landscape in the literature has not been fully elucidated yet, this review aims to examine the effects of commercially available nutraceuticals and their potential evidence and applications in dentistry.
MATERIALS AND METHODS
A scoping review was conducted following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR)" checklist. The electronic search was performed using PubMed/MEDLINE, EMBASE, the Cochrane Library, and Web of Science on March 2022. The inclusion criteria include humans, clinical trials, randomized controlled trials (RCT), reviews, and systematic reviews published over the last ten years.
RESULTS
18 studies met the eligibility criteria. There were 2 RCTs, 11 systematic reviews, and four narrative reviews. In most studies, the clinical indications were oral leucoplakia, periodontitis, osseointegration of implants, oral mucositis, oral clefts, and oral health. Probiotics, prebiotics, polyunsaturated fatty acids, and vitamins A, B, C, D, and E were the most common nutraceuticals used in dentistry.
CONCLUSIONS
Nutraceuticals are foods that, according to the literature, may be useful for preventing and treating dental diseases.
Topics: Humans; Dietary Supplements; Vitamins; Osseointegration; Vitamin A; Dentistry
PubMed: 37318464
DOI: 10.26355/eurrev_202306_32607 -
Infection and Immunity Mar 2022Bacterial infections routinely cause inflammation and thereby impair osseointegration of orthopedic implants. Acinetobacter spp., which cause osteomyelitis following...
Bacterial infections routinely cause inflammation and thereby impair osseointegration of orthopedic implants. Acinetobacter spp., which cause osteomyelitis following trauma, on or off the battlefield, were, however, reported to cause neither osteomyelitis nor osteolysis in rodents. We therefore compared the effects of Acinetobacter strain M2 to those of Staphylococcus aureus in a murine implant infection model. Sterile implants and implants with adherent bacteria were inserted in the femur of mice. Bacterial burden, levels of proinflammatory cytokines, and osseointegration were measured. All infections were localized to the implant site. Infection with either S. aureus or Acinetobacter strain M2 increased the levels of proinflammatory cytokines and the chemokine CCL2 in the surrounding femurs, inhibited bone formation around the implant, and caused loss of the surrounding cortical bone, leading to decreases in both histomorphometric and biomechanical measures of osseointegration. Genetic deletion of TLR2 and TLR4 from the mice partially reduced the effects of Acinetobacter strain M2 on osseointegration but did not alter the effects of S. aureus. This is the first report that Acinetobacter spp. impair osseointegration of orthopedic implants in mice, and the murine model developed for this study will be useful for future efforts to clarify the mechanism of implant failure due to Acinetobacter spp. and to assess novel diagnostic tools or therapeutic agents.
Topics: Acinetobacter baumannii; Animals; Cytokines; Mice; Osseointegration; Osteomyelitis; Staphylococcal Infections; Staphylococcus aureus
PubMed: 35099267
DOI: 10.1128/iai.00669-21