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The Journal of Bone and Joint Surgery.... Oct 2022Bisphosphonates limit resorption by inhibiting osteoclast formation and activation. They are removed during preparation of demineralized bone matrix (DBM) particles, but...
BACKGROUND
Bisphosphonates limit resorption by inhibiting osteoclast formation and activation. They are removed during preparation of demineralized bone matrix (DBM) particles, but it is not known if osteogenesis and incorporation of mineralized bone allografts from patients treated with oral bisphosphonates are affected in vivo.
METHODS
Human block allografts from 3 bisphosphonate-treated donors and 3 age and sex-matched control donors who had not received bisphosphonates were obtained (Musculoskeletal Transplant Foundation); one-half from each donor was demineralized. In the first study, 3 × 2-mm mineralized and demineralized cylindrical grafts were implanted bilaterally in the femoral metaphysis of 56 rats. In the second study, samples from each group were pooled, prepared as particles, and implanted bilaterally in the femoral marrow canal of 24 rats. Osseointegration, defined as native bone in contact with allograft, was assessed at 10 weeks by micro-computed tomography (CT) and histomorphometry.
RESULTS
Micro-CT showed greater bone volume in sites treated with demineralized samples compared with the control mineralized and bisphosphonate-exposed mineralized samples. More new bone was generated along the cortical-endosteal interface compared with mineralized samples. Histology showed significantly less new bone in contact with the mineralized bisphosphonate-exposed allograft (10.4%) compared with mineralized samples that did not receive bisphosphonates (22.8%) and demineralized samples (31.7% and 42.8%). A gap was observed between native bone and allograft in the bisphosphonate-exposed mineralized samples (0.50 mm 2 ). The gap area was significantly greater compared with mineralized samples that did not receive bisphosphonates (0.16 mm 2 ) and demineralized samples (0.10 and 0.03 mm 2 ).
CONCLUSIONS
Mineralized allografts were osseointegrated, but not remodeled or replaced by living bone, preventing full regeneration of the bone defect. Prior treatment of the donor with bisphosphonates affected osteogenesis, preventing osteointegration and remodeling of the allograft into the regenerating bone.
CLINICAL RELEVANCE
Clinical use of mineralized allografts from patients who had received bisphosphonate therapy needs to be evaluated; in this animal model, such grafts were not integrated into the host bone or remodeled, and full regeneration of the bone defects was prevented.
Topics: Animals; Bone Transplantation; Diphosphonates; Humans; Osseointegration; Osteogenesis; Rats; X-Ray Microtomography
PubMed: 35983995
DOI: 10.2106/JBJS.21.01489 -
Journal of Neuroscience Methods Jun 2023Neurophysiological studies with awake macaques typically require chronic cranial implants. Headpost and connector-chamber implants are used to allow head stabilization...
BACKGROUND
Neurophysiological studies with awake macaques typically require chronic cranial implants. Headpost and connector-chamber implants are used to allow head stabilization and to house connectors of chronically implanted electrodes, respectively.
NEW METHOD
We present long-lasting, modular, cement-free headpost implants made of titanium that consist of two pieces: a baseplate and a top part. The baseplate is implanted first, covered by muscle and skin and allowed to heal and osseointegrate for several weeks to months. The percutaneous part is added in a second, brief surgery. Using a punch tool, a perfectly round skin cut is achieved providing a tight fit around the implant without any sutures. We describe the design, planning and production of manually bent and CNC-milled baseplates. We also developed a remote headposting technique that increases handling safety. Finally, we present a modular, footless connector chamber that is implanted in a similar two-step approach and achieves a minimized footprint on the skull.
RESULTS
Twelve adult male macaques were successfully implanted with a headpost and one with the connector chamber. To date, we report no implant failure, great headpost stability and implant condition, in four cases even more than 9 years post-implantation.
COMPARISON WITH EXISTING METHODS
The methods presented here build on several related previous methods and provide additional refinements to further increase implant longevity and handling safety.
CONCLUSIONS
Optimized implants can remain stable and healthy for at least 9 years and thereby exceed the typical experiment durations. This minimizes implant-related complications and corrective surgeries and thereby significantly improves animal welfare.
Topics: Animals; Male; Macaca; Skull; Head; Neurophysiology; Electrodes, Implanted; Titanium; Osseointegration
PubMed: 37230259
DOI: 10.1016/j.jneumeth.2023.109899 -
Biomedical Papers of the Medical... Mar 2020Titanium surface treatment is a crucial process for achieving sufficient osseointegration of an implant into the bone. If the implant does not heal sufficiently, serious... (Review)
Review
Titanium surface treatment is a crucial process for achieving sufficient osseointegration of an implant into the bone. If the implant does not heal sufficiently, serious complications may occur, e.g. infection, inflammation, aseptic loosening of the implant, or the stress-shielding effect, as a result of which the implant may need to be reoperated. After a titanium graft has been implanted, several interactions are crucial in order to create a strong bone-implant connection. It is essential that cells adhere to the surface of the implant. Surface roughness has a significant influence on cell adhesion, and also on improving and accelerating osseointegration. Other highly important factors are biocompatibility and resistance to bacterial contamination. Bio-inertness of titanium is ensured by the protective film of titanium oxides that forms spontaneously on its surface. This film prevents the penetration of metal compounds, and it is well-adhesive for calcium and phosphate ions, which are necessary for the formation of the mineralized bone structure. Since the presence of the film alone is not sufficient for the biocompatibility of titanium, a suitable surface finish is required to create a firm bone-implant connection. In this review, we explain and compare the most widely-used methods for modulating the surface roughness of titanium implants in order to enhance cell adhesion on the surface of the implant, e.g. plasma spraying, sandblasting, acid etching, laser treatment, sol-gel etc., The methods are divided into three overlapping groups, according to the type of modification.
Topics: Coated Materials, Biocompatible; Humans; Osseointegration; Prostheses and Implants; Titanium
PubMed: 31907491
DOI: 10.5507/bp.2019.062 -
Journal of Nanobiotechnology Dec 2022Nanotopographical cues of bone implant surface has direct influences on various cell types during the establishment of osseointegration, a prerequisite of implant... (Review)
Review
Nanotopographical cues of bone implant surface has direct influences on various cell types during the establishment of osseointegration, a prerequisite of implant bear-loading. Given the important roles of monocyte/macrophage lineage cells in bone regeneration and remodeling, the regulation of nanotopographies on macrophages and osteoclasts has arisen considerable attentions recently. However, compared to osteoblastic cells, how nanotopographies regulate macrophages and osteoclasts has not been properly summarized. In this review, the roles and interactions of macrophages, osteoclasts and osteoblasts at different stages of bone healing is firstly presented. Then, the diversity and preparation methods of nanotopographies are summarized. Special attentions are paid to the regulation characterizations of nanotopographies on macrophages polarization and osteoclast differentiation, as well as the focal adhesion-cytoskeleton mediated mechanism. Finally, an outlook is indicated of coordinating nanotopographies, macrophages and osteoclasts to achieve better osseointegration. These comprehensive discussions may not only help to guide the optimization of bone implant surface nanostructures, but also provide an enlightenment to the osteoimmune response to external implant.
Topics: Osteoclasts; Osseointegration; Cues; Macrophages; Leukocyte Count
PubMed: 36463225
DOI: 10.1186/s12951-022-01721-1 -
Journal of Materials Science. Materials... May 2018Osseointegrated implants are frequently used in reconstructive surgery, both in the dental and orthopedic field, restoring physical function and improving the quality of... (Review)
Review
Osseointegrated implants are frequently used in reconstructive surgery, both in the dental and orthopedic field, restoring physical function and improving the quality of life for the patients. The bone anchorage is typically evaluated at micrometer resolution, while bone tissue is a dynamic composite material composed of nanoscale collagen fibrils and apatite crystals, with defined hierarchical levels at different length scales. In order to understand the bone formation and the ultrastructure of the interfacial tissue, analytical strategies needs to be implemented enabling multiscale and multimodal analyses of the intact interface. This paper describes a sample preparation route for successive analyses allowing assessment of the different hierarchical levels of interest, going from macro to nano scale and could be implemented on single samples. Examples of resulting analyses of different techniques on one type of implant surface is given, with emphasis on correlating the length scale between the different techniques. The bone-implant interface shows an intimate contact between mineralized collagen bundles and the outermost surface of the oxide layer, while bone mineral is found in the nanoscale surface features creating a functionally graded interface. Osteocytes exhibit a direct contact with the implant surface via canaliculi that house their dendritic processes. Blood vessels are frequently found in close proximity to the implant surface either within the mineralized bone matrix or at regions of remodeling.
Topics: Animals; Bone and Bones; Bone-Implant Interface; Calcification, Physiologic; Dental Implantation, Endosseous; Dental Implants; Humans; Materials Testing; Osseointegration; Surface Properties
PubMed: 29736606
DOI: 10.1007/s10856-018-6068-y -
The Kaohsiung Journal of Medical... Aug 2016Melatonin (N-acetyl-5-methoxy tryptamine) is a substance secreted by multiple organs in vertebrates. In addition to playing a part in the circadian cycle of the body,... (Review)
Review
Melatonin (N-acetyl-5-methoxy tryptamine) is a substance secreted by multiple organs in vertebrates. In addition to playing a part in the circadian cycle of the body, melatonin is known to have antioxidant, antiinflammatory, and antioncotic effects on human tissues. Oral cavity is affected by a number of conditions such as periodontitis, mucositis, cancers, and cytotoxicity from various drugs or biomaterials. Research has suggested that melatonin is effective in treating the aforementioned pathologies. Furthermore, melatonin has been observed to enhance osseointegration and bone regeneration. The aim of this review is to critically analyze and summarize the research focusing on the potential of melatonin in the field of oral medicine. Topical administration of melatonin has a positive effect on periodontal health and osseointegration. Furthermore, melatonin is particularly effective in improving the periodontal parameters of diabetic patients with periodontitis. Melatonin exerts a regenerative effect on periodontal bone and may be incorporated into of periodontal scaffolds. The cytotoxic effect of various drugs and dental materials may be countered by the antioxidant properties of melatonin. Topical administration of melatonin promotes the healing of tooth extraction sockets and may also impede the progression of oral cancer. Although, there are a number of current and potential applications of melatonin, further long term clinical and animal studies are needed to assess its efficacy. Moreover, the role of melatonin supplements in the management of periodontitis should also be assessed.
Topics: Animals; Bone Regeneration; Humans; Melatonin; Oral Medicine; Osseointegration; Periodontal Diseases
PubMed: 27523451
DOI: 10.1016/j.kjms.2016.06.005 -
JBJS Reviews Mar 2020Osseointegrated prostheses provide a rehabilitation option for amputees offering greater mobility, better satisfaction, and higher use than traditional socket... (Review)
Review
Osseointegrated prostheses provide a rehabilitation option for amputees offering greater mobility, better satisfaction, and higher use than traditional socket prostheses. There are several different osseointegrated implant designs, surgical techniques, and rehabilitation protocols with their own strengths and limitations. The 2 most prominent risks, infection and periprosthetic fracture, do not seem unacceptably frequent or insurmountable. Proximal amputations or situations leading to reduced mobility are exceptionally infrequent. Osseointegrated implants can be attached to advanced sensory and motor prostheses.
Topics: Amputees; Bone-Anchored Prosthesis; Humans; Osseointegration
PubMed: 32224634
DOI: 10.2106/JBJS.RVW.19.00043 -
Advanced Science (Weinheim,... Oct 2023Owing to their mechanical resilience and non-toxicity, titanium implants are widely applied as the major treatment modality for the clinical intervention against bone... (Review)
Review
Owing to their mechanical resilience and non-toxicity, titanium implants are widely applied as the major treatment modality for the clinical intervention against bone fractures. However, the intrinsic bioinertness of Ti and its alloys often impedes the effective osseointegration of the implants, leading to severe adverse complications including implant loosening, detachment, and secondary bone damage. Consequently, new Ti implant engineering strategies are urgently needed to improve their osseointegration after implantation. Remarkably, metalorganic frameworks (MOFs) are a class of novel synthetic material consisting of coordinated metal species and organic ligands, which have demonstrated a plethora of favorable properties for modulating the interfacial properties of Ti implants. This review comprehensively summarizes the recent progress in the development of MOF-coated Ti implants and highlights their potential utility for modulating the bio-implant interface to improve implant osseointegration, of which the discussions are outlined according to their physical traits, chemical composition, and drug delivery capacity. A perspective is also provided in this review regarding the current limitations and future opportunities of MOF-coated Ti implants for orthopedic applications. The insights in this review may facilitate the rational design of more advanced Ti implants with enhanced therapeutic performance and safety.
Topics: Osseointegration; Metal-Organic Frameworks; Titanium; Prostheses and Implants; Bone and Bones
PubMed: 37705110
DOI: 10.1002/advs.202303958 -
Cells Oct 2022Titanium-based implants are often utilized in oral implantology and craniofacial reconstructions. However, the biological inertness of machined titanium commonly results...
Titanium-based implants are often utilized in oral implantology and craniofacial reconstructions. However, the biological inertness of machined titanium commonly results in unsatisfactory osseointegration. To improve the osseointegration properties, we modified the titanium implants with nanotubular/superhydrophilic surfaces through anodic oxidation and thermal hydrogenation and evaluated the effects of the machined surfaces (M), nanotubular surfaces (Nano), and hydrogenated nanotubes (H-Nano) on osteogenesis and osseointegration in vitro and in vivo. After incubation of mouse bone marrow mesenchymal stem cells on the samples, we observed improved cell adhesion, alkaline phosphatase activity, osteogenesis-related gene expression, and extracellular matrix mineralization in the H-Nano group compared to the other groups. Subsequent in vivo studies indicated that H-Nano implants promoted rapid new bone regeneration and osseointegration at 4 weeks, which may be attributed to the active osteoblasts adhering to the nanotubular/superhydrophilic surfaces. Additionally, the Nano group displayed enhanced osteogenesis in vitro and in vivo at later stages, especially at 8 weeks. Therefore, we report that hydrogenated superhydrophilic nanotubes can significantly accelerate osteogenesis and osseointegration at an early stage, revealing the considerable potential of this implant modification for clinical applications.
Topics: Mice; Animals; Osseointegration; Titanium; Surface Properties; Nanotubes
PubMed: 36359812
DOI: 10.3390/cells11213417 -
JAMA Network Open Oct 2022Transcutaneous osseointegration post amputation (TOPA) creates a direct linkage between residual bone and an external prosthetic limb, providing superior mobility and... (Observational Study)
Observational Study
IMPORTANCE
Transcutaneous osseointegration post amputation (TOPA) creates a direct linkage between residual bone and an external prosthetic limb, providing superior mobility and quality of life compared with a socket prosthesis. The causes and potential risks of mortality after TOPA have not been investigated.
OBJECTIVE
To investigate the association between TOPA and mortality and assess the potential risk factors.
DESIGN, SETTING, AND PARTICIPANTS
This observational cohort study included all patients with amputation of a lower extremity who underwent TOPA between November 1, 2010, and October 31, 2021, at a specialty orthopedic practice and tertiary referral hospital in a major urban center. Patients lived on several continents and were followed up as long as 10 years.
EXPOSURES
Transcutaneous osseointegration post amputation, consisting of a permanent intramedullary implant passed transcutaneously through a stoma and connected to an external prosthetic limb.
MAIN OUTCOMES AND MEASURES
Death due to any cause. The hypotheses tested-that patient variables (sex, age, level of amputation, postosseointegration infection, and amputation etiology) may be associated with subsequent mortality-were formulated after initial data collection identifying which patients had died.
RESULTS
A total of 485 patients were included in the analysis (345 men [71.1%] and 140 women [28.9%]), with a mean (SD) age at osseointegration of 49.1 (14.6) years among living patients or 61.2 (12.4) years among patients who had died. Nineteen patients (3.9%) died a mean (SD) of 2.2 (1.7) years (range, 58 days to 5 years) after osseointegration, including 17 (3.5%) who died of causes unrelated to osseointegration (most commonly cardiac issues) and 2 (0.4%) who died of direct osseointegration-related complications (infectious complications), of which 1 (0.2%) was coclassified as a preexisting health problem exacerbated by osseointegration (myocardial infarction after subsequent surgery to manage infection). No deaths occurred intraoperatively or during inpatient recuperation or acute recovery after index osseointegration (eg, cardiopulmonary events). Kaplan-Meier survival analysis with log-rank comparison and Cox proportional hazards regression modeling identified increased age (hazard ratio, 1.06 [95% CI, 1.02-1.09]) and vascular (odds ratio [OR], 4.73 [95% CI, 1.35-16.56]) or infectious (OR, 3.87 [95% CI, 1.31-11.40]) amputation etiology as risk factors. Notable factors not associated with mortality risk included postosseointegration infection and male sex.
CONCLUSIONS AND RELEVANCE
These findings suggest that patients who have undergone TOPA rarely die of problems associated with the procedure but instead usually die of unrelated causes.
Topics: Adult; Amputation, Surgical; Artificial Limbs; Female; Humans; Lower Extremity; Male; Middle Aged; Osseointegration; Quality of Life
PubMed: 36227599
DOI: 10.1001/jamanetworkopen.2022.35074