Differential Effects of Neurectomy and Botox-induced Muscle Paralysis on Bone Phenotype and Titanium Implant Osseointegration

Deng, Jingyao; Cohen, David J.; Redden, James T.; McClure, Michael J.; Boyan, Barbara D.; Schwartz, Zvi

doi:10.1016/j.bone.2021.116145

Cited by 13 publications

(45 citation statements)

References 67 publications

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“…However, the osteo-immune response could be conditioned not only by local and systemic oxidative stress but also by the local innervation state (Figure 6). In support of the latter, recent in vivo experiments using Ti-implants in rat femur indicated strongly that neural regulation of bone directly modulates its formation and, as a consequence, osseointegration (131). The significance of this finding is not currently understood, but almost certainly there exist tight connections to the immune/ inflammatory system.…”

Section: Synergistic Activation Of Proinflammatory Pathwaysmentioning

confidence: 95%

Osteoimmune regulation underlies oral implant osseointegration and its perturbation

et al. 2023

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In the field of biomaterials, an endosseous implant is now recognized as an osteoimmunomodulatory but not bioinert biomaterial. Scientific advances in bone cell biology and in immunology have revealed a close relationship between the bone and immune systems resulting in a field of science called osteoimmunology. These discoveries have allowed for a novel interpretation of osseointegration as representing an osteoimmune reaction rather than a classic bone healing response, in which the activation state of macrophages ((M1–M2 polarization) appears to play a critical role. Through this viewpoint, the immune system is responsible for isolating the implant biomaterial foreign body by forming bone around the oral implant effectively shielding off the implant from the host bone system, i.e. osseointegration becomes a continuous and dynamic host defense reaction. At the same time, this has led to the proposal of a new model of osseointegration, the foreign body equilibrium (FBE). In addition, as an oral wound, the soft tissues are involved with all their innate immune characteristics. When implant integration is viewed as an osteoimmune reaction, this has implications for how marginal bone is regulated. For example, while bacteria are constitutive components of the soft tissue sulcus, if the inflammatory front and immune reaction is at some distance from the marginal bone, an equilibrium is established. If however, this inflammation approaches the marginal bone, an immune osteoclastic reaction occurs and marginal bone is removed. A number of clinical scenarios can be envisioned whereby the osteoimmune equilibrium is disturbed and marginal bone loss occurs, such as complications of aseptic nature and the synergistic activation of pro-inflammatory pathways (implant/wear debris, DAMPs, and PAMPs). Understanding that an implant is a foreign body and that the host reacts osteoimmunologically to shield off the implant allows for a distinction to be drawn between osteoimmunological conditions and peri-implant bone loss. This review will examine dental implant placement as an osteoimmune reaction and its implications for marginal bone loss.

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Section: Synergistic Activation Of Proinflammatory Pathwaysmentioning

confidence: 95%

Osteoimmune regulation underlies oral implant osseointegration and its perturbation

et al. 2023

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“…Most of the present studies focusing on this topic are animal experiments. There are several types of animal models which can be mainly divided into chemical, such as botox-induced models, and mechanical denervation like sciatic or other neurectomy ( Deng et al, 2021 ). For studies caring about not only the denervation but also the reinnervation, neurectomy models are used more often for second-stage nerve repair surgery.…”

Section: Introductionmentioning

confidence: 99%

Denervation-Related Neuromuscular Junction Changes: From Degeneration to Regeneration

Huang

Jiang

2022

Front. Mol. Neurosci.

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Neuromuscular junctions (NMJs) are the key interface between terminal nerves and targeted muscle, which undergo degeneration during denervation periods. Denervation-related NMJs changes limits the recovery level of nerve repair strategies. Insights into mechanisms behind neuromuscular junction degeneration and regeneration, following denervation and reinnervation, are of clinical value. Developing some therapies to maintain or protect structures and functions of NMJs may contribute to a better prognosis. Here, we reviewed previous studies of NMJs focusing on the morphological, functional, and molecular changes after denervation, and if those changes can be reversed after reinnervation. Also, we reviewed about the present probable strategies that have been applied clinically or could still be studied in targeting the neuromuscular junction protection or regeneration improvement.

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“…We previously reported that the osseointegration of modSLA implants, which have a hydrophilic surface, is impaired in the botox-compromised rat model [ 40 ]. In the present study, our goal was to focus on surface topography without the confounding variable of wettability, and the PT and SLAnano surfaces are both hydrophobic.…”

Section: Methodsmentioning

confidence: 99%

“…To assess whether Ti implant surface features would improve osseointegration under conditions where the bone was mechanically unloaded, we established a rat model using the neurotoxin botulinum toxin A (botox), which inhibits the release of acetylcholine from the neuromuscular junctions, causing paralysis. We found that osseointegration was drastically inhibited in the absence of mechanical stress [ 40 ].…”

Section: Introductionmentioning

confidence: 99%

“…We previously showed that the local delivery of human recombinant sema3A improved the osseointegration of Ti implants with a biomimetic surface topography placed transcortically in diabetic rat femurs, which have a similar bone phenotype to mechanically unloaded bone with respect to the loss of trabeculae in the metaphysis [ 40 , 41 ]. This suggested that sema3A might also improve implant integration in mechanically unloaded bone.…”

Section: Introductionmentioning

confidence: 99%

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Osseointegration of Titanium Implants in a Botox-Induced Muscle Paralysis Rat Model Is Sensitive to Surface Topography and Semaphorin 3A Treatment

et al. 2023

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Reduced skeletal loading associated with many conditions, such as neuromuscular injuries, can lead to bone fragility and may threaten the success of implant therapy. Our group has developed a botulinum toxin A (botox) injection model to imitate disease-reduced skeletal loading and reported that botox dramatically impaired the bone formation and osseointegration of titanium implants. Semaphorin 3A (sema3A) is an osteoprotective factor that increases bone formation and inhibits bone resorption, indicating its potential therapeutic role in improving osseointegration in vivo. We first evaluated the sema3A effect on whole bone morphology following botox injections by delivering sema3A via injection. We then evaluated the sema3A effect on the osseointegration of titanium implants with two different surface topographies by delivering sema3A to cortical bone defect sites prepared for implant insertion and above the implants after insertion using a copper-free click hydrogel that polymerizes rapidly in situ. Implants had hydrophobic smooth surfaces (PT) or multiscale biomimetic micro/nano topography (SLAnano). Sema3A rescued the botox-impaired bone formation. Furthermore, biomimetic Ti implants improved the bone-to-implant contact (BIC) and mechanical properties of the integrated bone in the botox-treated rats, which sema3A enhanced. This study demonstrated the value of biomimetic approaches combining multiscale topography and biologics in improving the clinical outcomes of implant therapy.

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Differential Effects of Neurectomy and Botox-induced Muscle Paralysis on Bone Phenotype and Titanium Implant Osseointegration

Cited by 13 publications

References 67 publications

Osteoimmune regulation underlies oral implant osseointegration and its perturbation

Osteoimmune regulation underlies oral implant osseointegration and its perturbation

Denervation-Related Neuromuscular Junction Changes: From Degeneration to Regeneration

Osseointegration of Titanium Implants in a Botox-Induced Muscle Paralysis Rat Model Is Sensitive to Surface Topography and Semaphorin 3A Treatment

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