Systemic drugs that influence titanium implant osseointegration

Apostu, Dragoș; Lucaciu, Ondine; Lucaciu, Gheorghe Dan Osvald; Crișan, Bogdan; Crisan, Liana; Băciuţ, Mihaela; Onişor, Florin; Băciuț, Grigore; Câmpian, Radu Septimiu; Bran, Simion

doi:10.1080/03602532.2016.1277737

Cited by 96 publications

(93 citation statements)

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“…Although simvastatin has been showed to improve osseointegration around titanium implant, the appropriate administration route on promotion of osseointegration should be investigated (Apostu et al, ). With oral administration, simvastatin is not well absorbed, and less than 5% of the oral dose is taken up in the systemic circulation (Park, ).…”

Section: Discussionmentioning

confidence: 99%

“…We outlined the mature bone by yellow dotted lines and observed the effect of simvastatin on osseointegration by evaluating the mount of new bone formation. In addition, to further detect the new bone formation, we conducted fluorochrome labelling histomorphometrical analysis and examined the percentage of alizarin Red S and calcein fluorescent labellings, which represented the mineralization level of new bone (Apostu et al, ; Lee et al, ).…”

Section: Discussionmentioning

confidence: 99%

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Simvastatin improves oral implant osseointegration via enhanced autophagy and osteogenesis of BMSCs and inhibited osteoclast activity

Shi

et al. 2018

J Tissue Eng Regen Med

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Dental implants have become a widely accepted and successful treatment for fully and partially edentulous patients. Simvastatin has been applied to improve and accelerate the osseointegration of implants by increasing the quantity and quality of bone tissue. However, its potential mechanism has not been elucidated completely. Here, we found that simvastatin significantly enhanced the autophagy level of jaw-derived bone marrow stromal cells (BMSCs) and alleviated production of reactive oxygen species under unfavourable conditions. Simvastatin promoted osteogenic differentiation of BMSCs via enhanced autophagy. Furthermore, simvastatin inhibited the bone resorption activity of osteoclasts. With the use of a rat model of oral implant osseointegration, we found local injection of simvastatin displayed more new bone formation at the interface of the bone and implant compared with that of oral administration. Fluorochrome labelling histomorphometrical analysis and micro-CT also showed that simvastatin promoted the osseointegration of implants. Notably, fewer activated osteoclasts were observed in the region of osseointegration of implants from the simvastatin treatment groups, especially the local delivery of simvastatin. Collectively, our results revealed that simvastatin can increase osteoblastic differentiation of BMSCs via enhanced autophagy and decreased osteoclast activity. Thus, simvastatin could be a viable and promising drug to improve and even accelerate the osseointegration of a dental implant.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Simvastatin improves oral implant osseointegration via enhanced autophagy and osteogenesis of BMSCs and inhibited osteoclast activity

Shi

et al. 2018

J Tissue Eng Regen Med

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“…In addition, currently available drugs have been tested for their efficacy to improve bone metabolism in osteoporosis. Common beliefs are that aseptic prosthetic loosening could be prevented if implants have improved osseointegration [215]. These drugs are in general classified in two major categories: (1) anabolic, which targets osteoblast activity or number to improve bone mass [216], or (2) anti-catabolic, targeting osteoclast formation and activity [217].…”

Section: Drug Screening In the Presence Of Mechanical Loading Is Critmentioning

confidence: 99%

Mechanisms of mechanically induced Osteoclastogenesis : in a novel in vitro model for bone implant loosening

Bratengeier

2019

Linköping University Medical Dissertations

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Total joint arthroplasty is the primary intervention in the treatment of end-stage osteoarthritis.The majority of joint arthroplasties will last the whole lifetime. However, in some patients, the replacement will fail during their lifetime requiring a revision of the implant. These revisions are strenuous for the patient and costly for health care. To avoid a revision, therefore, is the uttermost goal of modern orthopedics. Joint replacement at a younger age, in combination with a more active lifestyle, increases the need for an early revision of the joint prosthesis. The main reason for revision surgeries is aseptic loosening, a condition where the prosthesis is loosening due to bone degradation at the peri-prosthetic interface in the absence of infections. The most well-established pathological mechanism for aseptic loosening is related to wear particles, generated from different parts of the prosthesis that will trigger bone degradation and bone loss.In addition, early micromotions of the prosthesis and resulting local pressurized fluid flow in the peri-prosthetic interface (supraphysiological loading) have also been identified as a cause for aseptic loosening. However, it remains unknown what cells are the primary responders to supraphysiological loading, and what underlying physical, cellular and molecular mechanism that triggers osteoclast differentiation and osteolysis.The main goal of this thesis is to shed light on three currently unknown aspects of mechanical loading-induced peri-prosthetic osteolysis, leading to aseptic loosening of orthopedic prostheses: (1)Which cells are the primary responder to supraphysiological loading? (2)What characteristics of the mechanical stimulus induce an osteo-protective or osteo-destructive response? (3)Which cellular mechano-sensing mechanisms are involved in an osteo-destructive response?The first study focused on the creation and validation of a novel in vitro model for mechanical loading-induced bone degradation. This model simulates the mechanical (over)loading conditions around a loosening prosthesis, as observed in the clinics, and in animal models for mechanical induced osteolysis. Using the MLO-Y4 osteocyte-like cell line, we verified that osteocytes exposed to supraphysiological mechanical loading in our model induce differentiation of progenitor cells into osteoclasts by direct cell-to-cell communication and through the release of soluble factors. This was accompanied by the release of an increased concentration of nitric oxide and higher expression of membrane-bound RANKL, while the concentration of soluble RANKL was not altered. These findings confirm the successful translation of mechanical-induced bone loss to an in vitro model for bone implant loosening. Many people have supported me during my time as a Ph.D. student and I am deeply grateful. I want to highlight a few people specifically, as they contributed significantly to my success: Anna Fahlgren Thank you for giving me the opportunity to become part of your research team and guiding me to become a c...

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“…Consequently, there has been a wealth of research interest in seeking ways of improving osseointegration. Such approaches include the development of Ti technologies that promote more rapid and superior rates of integration by enhancing, for example, the activity of bone-forming osteoblast cells at the Ti surface [5].…”

Section: Introductionmentioning

confidence: 99%

Polydopamine-Lysophosphatidate-Functionalised Titanium: A Novel Hybrid Surface Finish for Bone Regenerative Applications

et al. 2020

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Aseptic loosening of total joint replacements (TJRs) continues to be the main cause of implant failures. The socioeconomic impact of surgical revisions is hugely significant; in the United Kingdom alone, it is estimated that £135m is spent annually on revision arthroplasties. Enhancing the longevity of titanium implants will help reduce the incidence and overall cost of failed devices. In realising the development of a superior titanium (Ti) technology, we took inspiration from the growing interest in reactive polydopamine thin films for biomaterial surface functionalisations. Adopting a “one-pot” approach, we exposed medical-grade titanium to a mildly alkaline solution of dopamine hydrochloride (DHC) supplemented with (3S)1-fluoro-3-hydroxy-4-(oleoyloxy)butyl-1-phosphonate (FHBP), a phosphatase-resistant analogue of lysophosphatidic acid (LPA). Importantly, LPA and selected LPA analogues like FHBP synergistically cooperate with calcitriol to promote human osteoblast formation and maturation. Herein, we provide evidence that simply immersing Ti in aqueous solutions of DHC-FHBP afforded a surface that was superior to FHBP-Ti at enhancing osteoblast maturation. The facile step we have taken to modify Ti and the biological performance of the final surface finish are appealing properties that may attract the attention of implant manufacturers in the future.

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Systemic drugs that influence titanium implant osseointegration

Cited by 96 publications

References 93 publications

Simvastatin improves oral implant osseointegration via enhanced autophagy and osteogenesis of BMSCs and inhibited osteoclast activity

Simvastatin improves oral implant osseointegration via enhanced autophagy and osteogenesis of BMSCs and inhibited osteoclast activity

Mechanisms of mechanically induced Osteoclastogenesis : in a novel in vitro model for bone implant loosening

Polydopamine-Lysophosphatidate-Functionalised Titanium: A Novel Hybrid Surface Finish for Bone Regenerative Applications

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