» The purpose of this article was to review the multidisciplinary, team-based approach necessary for the optimal management of patients with limb loss undergoing osseointegration surgery.» In this study, we describe the interdisciplinary process of screening, counseling, and surgical and rehabilitation considerations with an emphasis on principles rather than specific implants or techniques.» Integrated perioperative management and long-term surveillance are crucial to ensure the best possible outcomes.» We hope this model will service as an implant-agnostic guide to others seeking to development an osseointegration center of excellence.

Considering the biological activity of osteoblasts is crucial when devising new approaches to enhance the osseointegration of implant surfaces, as their behavior profoundly influences clinical outcomes. An established inverse correlation exists between osteoblast proliferation and their functional differentiation, which constrains the rapid generation of a significant amount of bone. Examining the surface morphology of implants reveals that roughened titanium surfaces facilitate rapid but thin bone formation, whereas smooth, machined surfaces promote greater volumes of bone formation albeit at a slower pace. Consequently, osteoblasts differentiate faster on roughened surfaces but at the expense of proliferation speed. Moreover, the attachment and initial spreading behavior of osteoblasts are notably compromised on microrough surfaces. This review delves into our current understanding and recent advances in nanonodular texturing, meso-scale texturing, and UV photofunctionalization as potential strategies to address the \"biological dilemma\" of osteoblast kinetics, aiming to improve the quality and quantity of osseointegration. We discuss how these topographical and physicochemical strategies effectively mitigate and even overcome the dichotomy of osteoblast behavior and the biological challenges posed by microrough surfaces. Indeed, surfaces modified with these strategies exhibit enhanced recruitment, attachment, spread, and proliferation of osteoblasts compared to smooth surfaces, while maintaining or amplifying the inherent advantage of cell differentiation. These technology platforms suggest promising avenues for the development of future implants.

Dental implant therapy, established as standard-of-care nearly three decades ago with the advent of microrough titanium surfaces, revolutionized clinical outcomes through enhanced osseointegration. However, despite this pivotal advancement, challenges persist, including prolonged healing times, restricted clinical indications, plateauing success rates, and a notable incidence of peri-implantitis. This review explores the biological merits and constraints of microrough surfaces and evaluates the current landscape of nanofeatured dental implant surfaces, aiming to illuminate strategies for addressing existing impediments in implant therapy. Currently available nanofeatured dental implants incorporated nano-structures onto their predecessor microrough surfaces. While nanofeature integration into microrough surfaces demonstrates potential for enhancing early-stage osseointegration, it falls short of surpassing its predecessors in terms of osseointegration capacity. This discrepancy may be attributed, in part, to the inherent \"dichotomy kinetics\" of osteoblasts, wherein increased surface roughness by nanofeatures enhances osteoblast differentiation but concomitantly impedes cell attachment and proliferation. We also showcase a controllable, hybrid micro-nano titanium model surface and contrast it with commercially-available nanofeatured surfaces. Unlike the commercial nanofeatured surfaces, the controllable micro-nano hybrid surface exhibits superior potential for enhancing both cell differentiation and proliferation. Hence, present nanofeatured dental implants represent an evolutionary step from conventional microrough implants, yet they presently lack transformative capacity to surmount existing limitations. Further research and development endeavors are imperative to devise optimized surfaces rooted in fundamental science, thereby propelling technological progress in the field.

The process of osteointegration of dental implants is a biological process. Systemic therapy can interfere with this process, affecting the growth and breakdown processes of the bone and ultimately leading to implant failure. This literature review focuses on specific groups of systemic drugs that directly impact osteointegration. The research in electronic literature was conducted using the National Library of Medicine\'s PubMed/MEDLINE database from March 2000 to February 2024. The following MeSH (Medical Subject Headings) terms were used: \"implant osseointegration,\" \"bisphosphonates,\" \"non-steroidal anti-inflammatory drugs,\" \"glucocorticoids,\" \"proton pump inhibitors,\" and \"selective serotonin reuptake inhibitors (SSRIs).\" This search yielded 1,258 articles on implant osseointegration. Among these, 30 articles met our criteria for implant osseointegration and bisphosphonates, 2 articles for non-steroidal anti-inflammatory drugs (NSAIDs), 7 articles for glucocorticoids, 14 articles for proton pump inhibitors (PPIs), and 14 articles for selective serotonin reuptake inhibitors (SSRIs). Clinicians considering implant therapy should be mindful of potential medication-related implant failures. The present systematic review has identified an association between proton pump inhibitors (PPIs), nonsteroidal anti-inflammatory drugs (NSAIDs), selective serotonin reuptake inhibitors (SSRIs), glucocorticoids, and bisphosphonates with an increased implant failure rate.

OBJECTIVE: The aim of this study was to explore the effect of depression and selective serotonin reuptake inhibitors on implant osseointegration and bone healing.
METHODS: Forty-eight 6- to 8-week-old SPF Sprague-Dawley male rats were randomly divided into four groups: the Control group, the Fluoxetine group, the Depression group and the De&Flu group. The rats in the Depression group and the De&Flu group were subjected to a depression modelling process, and the rats in the Control group and the Fluoxetine group were raised normally. Then, a titanium implant was placed in the right tibia of each rat. In the Fluoxetine group and De&Flu group, fluoxetine was injected subcutaneously daily, while subcutaneously injecting physiological saline in the Control group and Depression group. Collecting serum from the rats used for ELISA. The surgical area was cut for microcomputed tomography and histology observation.
RESULTS: After 12 weeks, bone mineral density was lower in the De&Flu group than in the Control group, Depression group and Fluoxetine group. Bone mineral density was also lower in the Depression group and the Fluoxetine group than in the Control group. The percentage of bone-implant contact (BIC%) in De&Flu rats was lower than in the Control, Depression and Fluoxetine groups. The BIC% in the Depression group and the Fluoxetine group was lower than in the Control group.
CONCLUSIONS: Depression and fluoxetine negatively affect bone density and implant osseointegration independently, and this damaging effect is exacerbated when both factors are present. The mechanism may be related to the dysregulation of the hypothalamic-pituitary-adrenal axis and inflammation in the body.

Given the hierarchical nature of bone and bone interfaces, osseointegration, namely the formation of a direct bone-implant contact, is best evaluated using a multiscale approach. However, a trade-off exists between field of view and spatial resolution, making it challenging to image large volumes with high resolution. In this study, we combine established electron microscopy techniques to probe bone-implant interfaces at the microscale and nanoscale with plasma focused ion beam-scanning electron microscopy (PFIB-SEM) tomography to evaluate osseointegration at the mesoscale. This characterization workflow is demonstrated for bone response to an additively manufactured Ti-6Al-4V implant which combines engineered porosity to facilitate bone ingrowth and surface functionalization via genistein, a phytoestrogen, to counteract bone loss in osteoporosis. SEM demonstrated new bone formation at the implant site, including in the internal implant pores. At the nanoscale, scanning transmission electron microscopy and energy-dispersive X-ray spectroscopy confirmed the gradual nature of the bone-implant interface. By leveraging mesoscale analysis with PFIB-SEM tomography that captures large volumes of bone-implant interface with nearly nanoscale resolution, the presence of mineral ellipsoids varying in size and orientation was revealed. In addition, a well-developed lacuno-canalicular network and mineralization fronts directed both towards the implant and away from it were highlighted.

Type 2 diabetes (T2D) is on a notable rise worldwide, which leads to unfavorable outcomes during implant treatments. Surface modification of implants and exosome treatment have been utilized to enhance osseointegration. However, there has been insufficient approach to improve adverse osseointegration in T2D conditions. In this study, we successfully loaded TNF-α-treated mesenchymal stem cell (MSC)-derived exosomes onto micro/nano-network titanium (Ti) surfaces. TNF-α-licensed exosome-integrated titanium (TNF-exo-Ti) effectively enhanced M2 macrophage polarization in hyperglycemic conditions, with increased secretion of anti-inflammatory cytokines and decreased secretion of pro-inflammatory cytokines. In addition, TNF-exo-Ti pretreated macrophage further enhanced angiogenesis and osteogenesis of endothelial cells and bone marrow MSCs. More importantly, TNF-exo-Ti markedly promoted osseointegration in T2D mice. Mechanistically, TNF-exo-Ti activated macrophage autophagy to promote M2 polarization through inhibition of the PI3K/AKT/mTOR pathway, which could be abolished by PI3K agonist. Thus, this study established TNF-α-licensed exosome-immobilized titanium surfaces that could rectify macrophage immune states and accelerate osseointegration in T2D conditions.

OBJECTIVE: This study was conducted to evaluate the effects of plasma treatment of sandblasted and acid-etched (SLA) titanium implants on surface cleansing and osseointegration in a beagle model.
METHODS: For morphological analysis and XPS analysis, scanning electron microscope and x-ray photoelectron spectroscopy were used to analyze the surface topography and chemical compositions of implant before and after plasma treatment. For this animal experiment, twelve SLA titanium implants were divided into two groups: a control group (untreated implants) and a plasma group (implants treated with plasma). Each group was randomly located in the mandibular bone of the beagle dog (n = 6). After 8 weeks, the beagle dogs were sacrificed, and volumetric analysis and histometric analysis were performed within the region of interest.
RESULTS: In morphological analysis, plasma treatment did not alter the implant surface topography or cause any physical damage. In XPS analysis, the atomic percentage of carbon at the inspection point before the plasma treatment was 34.09%. After the plasma treatment, it was reduced to 18.74%, indicating a 45% reduction in carbon. In volumetric analysis and histometric analysis, the plasma group exhibited relatively higher mean values for new bone volume (NBV), bone to implant contact (BIC), and inter-thread bone density (ITBD) compared to the control group. However, there was no significant difference between the two groups (P > .05).
CONCLUSIONS: Within the limits of this study, plasma treatment effectively eliminated hydrocarbons without changing the implant surface.

The bone turnover capability influences the acquisition and maintenance of osseointegration. The architectures of osteocyte three-dimensional (3D) networks determine the direction and activity of bone turnover through osteocyte intercellular crosstalk, which exchanges prostaglandins through gap junctions in response to mechanical loading. Titanium nanosurfaces with anisotropically patterned dense nanospikes promote the development of osteocyte lacunar-canalicular networks. We investigated the effects of titanium nanosurfaces on intercellular network development and regulatory capabilities of bone turnover in osteocytes under cyclic compressive loading. MLO-Y4 mouse osteocyte-like cell lines embedded in type I collagen 3D gels on titanium nanosurfaces promoted the formation of intercellular networks and gap junctions even under static culture conditions, in contrast to the poor intercellular connectivity in machined titanium surfaces. The osteocyte 3D network on the titanium nanosurfaces further enhanced gap junction formation after additional culturing under cyclic compressive loading simulating masticatory loading, beyond the degree observed on machined titanium surfaces. A prostaglandin synthesis inhibitor cancelled the dual effects of titanium nanosurfaces and cyclic compressive loading on the upregulation of gap junction-related genes in the osteocyte 3D culture. Supernatants from osteocyte monolayer culture on titanium nanosurfaces promoted osteocyte maturation and intercellular connections with gap junctions. With cyclic loading, titanium nanosurfaces induced expression of the regulatory factors of bone turnover in osteocyte 3D cultures, toward higher osteoblast activation than that observed on machined surfaces. Titanium nanosurfaces with anisotropically patterned dense nanospikes promoted intercellular 3D network development and regulatory function toward osteoblast activation in osteocytes activated by cyclic compressive loading, through intercellular crosstalk by prostaglandin.

OBJECTIVE: Studies have not been done to evaluate the peri-implant stress exerted by materials(like PEEK and resin matrix ceramics) in different osseointegration conditions. To investigate the effect of different occlusal materials on peri-implant stress distribution with different osseointegration condition using finite element analysis.
METHODS: Eighteen different 3D FEA models of implant fixed with abutment were created involving 6 different occlusal materials (Heat cured temporary acrylic resin (PMMA), Bis-GMA, PEEK, Lithium disilicate, Resin matrix ceramics and translucent Zirconia) and different osseointegrated conditions (50%, 75%, 100%).
METHODS: Models were subjected to loading vertically and obliquely followed by evaluation of stress distribution.
METHODS: The results of the simulation obtained were analysed in terms of Von mises, maximum principal and minimal principal stresses using descriptive stastistics.
RESULTS: PMMA (40.14 MPa on vertical loading and 66 MPa on oblique loading) resulted in the highest stresses and lithium disilicate (24 MPa on vertical loading and 52.40 MPa on oblique loading) resulted in least stresses among all the crown materials. Upon oblique loading, von Mises stress increases except for translucent zirconia and lithium disilicate (52.444 MPa on 50%, 47.733 MPa on 75%, and 43.973 MPa on 100% osseointegration). Minimal principal stress values decreased with increase in osseointegration upon oblique loading for PMMA, BisGMA, and PEEK.
CONCLUSIONS: Translucent zirconia and lithium disilicate offer a better stress transmission. Minimal principal stress values of PEEK and BisGMA decreased with increasing osseointegration.