-
Journal of Biomedical Materials... Mar 2022Endosseous implant surface topography directly affects adherent cell responses following implantation. The aim of this study was to examine the impact of nanoscale...
Endosseous implant surface topography directly affects adherent cell responses following implantation. The aim of this study was to examine the impact of nanoscale topographic modification of titanium implants on Osterix gene expression since this gene has been reported as key factor for bone formation. Titanium implants with smooth and nanoscale topographies were implanted in the femurs of Osterix-Cherry mice for 1-21 days. Implant integration was evaluated using scanning electron microscopy (SEM) to evaluate cell adhesion on implant surfaces, histology, and nanotomography (NanoCT) to observe and quantify the formed bone-to-implant interface, flow cytometry to quantify of Osterix expressing cells in adjacent tissues, and real-time PCR (qPCR) to quantify the osteoinductive and osteogenic gene expression of the implant-adherent cells. SEM revealed topography-dependent adhesion of cells at early timepoints. NanoCT demonstrated greater bone formation at nanoscale implants and interfacial osteogenesis was confirmed histologically at 7 and 14 days for both smooth and nanosurface implants. Flow cytometry revealed greater numbers of Osterix positive cells in femurs implanted with nanoscale versus smooth implants. Compared to smooth surface implants, nanoscale surface adherent cells expressed higher levels of Osterix (Osx), Alkaline phosphatase (Alp), Paired related homeobox (Prx1), Dentin matrix protein 1 (Dmp1), Bone sialoprotein (Bsp), and Osteocalcin (Ocn). In conclusion, nanoscale surface implants demonstrated greater bone formation associated with higher levels of Osterix expression over the 21-day healing period with direct evidence of surface-associated gene regulation involving a nanoscale-mediated osteoinductive pathway that utilizes Osterix to direct adherent cell osteoinduction.
Topics: Animals; Dental Implants; Mice; Osseointegration; Osteogenesis; Prostheses and Implants; Surface Properties; Titanium
PubMed: 34672417
DOI: 10.1002/jbm.a.37323 -
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 -
Tissue Engineering. Part B, Reviews Oct 2019Bone regeneration procedures in clinics and bone tissue engineering stand on three pillars: osteoconduction, osteoinduction, and stem cells. In the last two decades, the... (Review)
Review
Bone regeneration procedures in clinics and bone tissue engineering stand on three pillars: osteoconduction, osteoinduction, and stem cells. In the last two decades, the focus in this field has been on osteoinduction, which is realized by the use of bone morphogenetic proteins and the application of mesenchymal stem cells to treat bone defects. However, osteoconduction was reduced to a surface phenomenon because the supposedly ideal pore size of osteoconductive scaffolds was identified in the 1990s as 0.3-0.5 mm in diameter, forcing bone formation to occur predominantly on the surface. Meanwhile, additive manufacturing has evolved as a new tool to realize designed microarchitectures in bone substitutes, thereby enabling us to study osteoconduction as a true three-dimensional phenomenon. Moreover, by additive manufacturing, wide-open porous scaffolds can be produced in which bone formation occurs distant to the surface at a superior bony defect-bridging rate enabled by highly osteoconductive pores 1.2 mm in diameter. This review provides a historical overview and an updated definition of osteoconduction and related terms. In addition, it shows how additive manufacturing can be instrumental in studying and optimizing osteoconduction of bone substitutes, and provides novel optimized features and boundaries of osteoconductive microarchitectures. Impact Statement This review updates the definition of osteoconduction and draws clear lines to discriminate between osteoconduction, osseointegration, and osteoinduction. Moreover, additively manufactured libraries of scaffolds revealed that: osteoconduction is more a three-dimensional than a surface phenomenon; microarchitecture dictates defect bridging, which is the measure for osteoconduction; pore diameter or the diagonal of lattice microarchitectures of osteoconductive bone substitutes should be ∼1.2 mm.
Topics: Animals; Bone Regeneration; Bone and Bones; Humans; Mesenchymal Stem Cells; Osseointegration; Osteogenesis; Tissue Engineering; Tissue Scaffolds
PubMed: 30997857
DOI: 10.1089/ten.TEB.2019.0047 -
International Journal of Nanomedicine 2022Titanium implants have been widely applied in dentistry and orthopedics due to their biocompatibility and resistance to mechanical fatigue. TiO nanotube arrays (TiO... (Review)
Review
Titanium implants have been widely applied in dentistry and orthopedics due to their biocompatibility and resistance to mechanical fatigue. TiO nanotube arrays (TiO NTAs) on titanium implant surfaces have exhibited excellent biocompatibility, bioactivity, and adjustability, which can significantly promote osseointegration and participate in its entire path. In this review, to give a comprehensive understanding of the osseointegration process, four stages have been divided according to pivotal biological processes, including protein adsorption, inflammatory cell adhesion/inflammatory response, additional relevant cell adhesion and angiogenesis/osteogenesis. The impact of TiO NTAs on osseointegration is clarified in detail from the four stages. The nanotubular layer can manipulate the quantity, the species and the conformation of adsorbed protein. For inflammatory cells adhesion and inflammatory response, TiO NTAs improve macrophage adhesion on the surface and induce M2-polarization. TiO NTAs also facilitate the repairment-related cells adhesion and filopodia formation for additional relevant cells adhesion. In the angiogenesis and osteogenesis stage, TiO NTAs show the ability to induce osteogenic differentiation and the potential for blood vessel formation. In the end, we propose the multi-dimensional regulation of TiO NTAs on titanium implants to achieve highly efficient manipulation of osseointegration, which may provide views on the rational design and development of titanium implants.
Topics: Adsorption; Osseointegration; Osteogenesis; Surface Properties; Titanium
PubMed: 35518451
DOI: 10.2147/IJN.S362720 -
Sovremennye Tekhnologii V Meditsine 2021was to study the influence of pore size and the presence of a biologically active calcium phosphate coating in porous 3D printed titanium implants on the process of...
UNLABELLED
was to study the influence of pore size and the presence of a biologically active calcium phosphate coating in porous 3D printed titanium implants on the process of integration with the bone tissue.
MATERIALS AND METHODS
Samples of cylindrical implants with three different pore diameters (100, 200, and 400 μm) were fabricated from titanium powder on the Arcam 3D printer (Sweden) using electron beam melting technology. A calcium phosphate coating with a thickness of 20±4 μm was applied to some of the products by microarc oxidation. Cytotoxicity of the implants was determined on human dermal fibroblast cultures. The samples were implanted in the femoral bones of 36 rabbits . The animals were divided into 6 groups according to the bone implant samples. The prepared samples and peri-implant tissues were studied on days 90 and 180 after implantation using scanning electron microscopy and histological methods.
RESULTS
All samples under study were found to be non-toxic and well biocompatible with the bone tissue. There were revealed no differences between coated and non-coated implants of 100 and 200 μm pore diameters in terms of their histological structure, intensity of vascularization in the early stages, and bone formation in the later stages. Samples with pore diameters of 100 and 200 μm were easily removed from the bone tissue, the depth of bone growth into the pores of the implant was lower than in the samples with pore diameter of 400 μm (p<0.001). There were differences between coated and non-coated samples of 400 μm pore diameter, which was expressed in a more intensive osseointegration of samples with calcium phosphate coating (p<0.05).
CONCLUSION
The optimal surface characteristics of the material for repairing bone defects are a pore diameter of 400 μm and the presence of a calcium phosphate coating.
Topics: Animals; Calcium Phosphates; Coated Materials, Biocompatible; Osseointegration; Porosity; Rabbits; Surface Properties; Titanium
PubMed: 34513077
DOI: 10.17691/stm2021.13.2.06 -
International Journal of Molecular... Oct 2021The present study aimed to investigate the effect of β‑receptor blocker propranolol on early osseointegration of pure titanium implants and the underlying molecular...
The present study aimed to investigate the effect of β‑receptor blocker propranolol on early osseointegration of pure titanium implants and the underlying molecular regulatory mechanisms. An implant osseointegration model using the tibial metaphysis of New Zealand rabbits was established. The rabbits were divided into control and low‑, medium‑ and high‑dose propranolol groups. The formation of implant osseointegration was detected by X‑ray scanning. Mesenchymal stem cells (MSCs) and osteoblasts (OBs) were isolated and cultured , isoproterenol was supplemented to simulate sympathetic action and propranolol was subsequently administrated. The effect of propranolol on cell proliferation and osteogenic differentiation were assessed by EdU, flow cytometry, alizarin red staining and alkaline phosphatase (ALP) detection. The expression levels of bone morphogenetic protein (BMP)2, RUNX family transcription factor (RunX)2, collagen (COL)‑1, osteocalcin (OCN) and β2‑adrenergic receptor (AR) were detected by immunofluorescence, reverse transcription‑quantitative PCR and western blot assay. Propranolol effectively promoted implant osseointegration , facilitated proliferation of OBs, inhibited proliferation of MSCs and enhanced osteogenic differentiation of OBs and MSCs. The calcium content and ALP activity of cells treated with propranolol were markedly higher than in the control group. Propranolol also elevated mRNA and protein expression levels of BMP2, RunX2, COL‑1 and OCN in tissue and cells, and decreased the expression of β2‑AR. The present study demonstrated that the β‑receptor blocker propranolol promoted osteogenic differentiation of OBs and MSCs and enhanced implant osseointegration. The present study provided a novel insight into the application and regulatory mechanisms of propranolol.
Topics: Animals; Bone Morphogenetic Protein 2; Cell Differentiation; Cell Proliferation; Cells, Cultured; Core Binding Factor Alpha 1 Subunit; Gene Expression Regulation; Male; Mesenchymal Stem Cells; Osseointegration; Osteoblasts; Osteocalcin; Osteogenesis; Propranolol; Rabbits; Receptors, Adrenergic, beta-2; Titanium
PubMed: 34414453
DOI: 10.3892/ijmm.2021.5024 -
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 -
Burns : Journal of the International... Aug 2023Transcutaneous osseointegration for amputees (TOFA) surgically implants a prosthetic anchor into the residual limb's bone, enabling direct skeletal connection to a...
OBJECTIVE
Transcutaneous osseointegration for amputees (TOFA) surgically implants a prosthetic anchor into the residual limb's bone, enabling direct skeletal connection to a prosthetic limb and eliminating the socket. TOFA has demonstrated significant mobility and quality of life benefits for most amputees, but concerns regarding its safety for patients with burned skin have limited its use. This is the first report of the use of TOFA for burned amputees.
METHODS
Retrospective chart review was performed of five patients (eight limbs) with a history of burn trauma and subsequent osseointegration. The primary outcome was adverse events such as infection and additional surgery. Secondary outcomes included mobility and quality of life changes.
RESULTS
The five patients (eight limbs) had an average follow-up time of 3.8 ± 1.7 (range 2.1-6.6) years. We found no issues of skin compatibility or pain associated with the TOFA implant. Three patients underwent subsequent surgical debridement, one of whom had both implants removed and eventually reimplanted. K-level mobility improved (K2 +, 0/5 vs 4/5). Other mobility and quality of life outcomes comparisons are limited by available data.
CONCLUSION
TOFA is safe and compatible for amputees with a history of burn trauma. Rehabilitation capacity is influenced more by the patient's overall medical and physical capacity than their specific burn injury. Judicious use of TOFA for appropriately selected burn amputees seems safe and merited.
Topics: Humans; Amputees; Osseointegration; Amputation, Surgical; Artificial Limbs; Retrospective Studies; Quality of Life; Burns
PubMed: 36907716
DOI: 10.1016/j.burns.2023.02.006 -
Journal of Dental Research Sep 2021Osseointegration of dental, craniofacial, and orthopedic implants is critical for their long-term success. Multifunctional surface treatment of implants was found to...
Osseointegration of dental, craniofacial, and orthopedic implants is critical for their long-term success. Multifunctional surface treatment of implants was found to significantly improve cell adhesion and induce osteogenic differentiation of dental-derived stem cells in vitro. Moreover, local and sustained release of antibiotics via nanolayers from the surface of implants can present unparalleled therapeutic benefits in implant dentistry. Here, we present a layer-by-layer surface treatment of titanium implants capable of incorporating BMP-2-mimicking short peptides and gentamicin to improve their osseointegration and antibacterial features. Additionally, instead of conventional surface treatments, we employed polydopamine coating before layer-by-layer assembly to initiate the formation of the nanolayers on rough titanium surfaces. Cytocompatibility analysis demonstrated that modifying the titanium implant surface with layer-by-layer assembly did not have adverse effects on cellular viability. The implemented nanoscale coating provided sustained release of osteoinductive peptides with an antibacterial drug. The surface-functionalized implants showed successful osteogenic differentiation of periodontal ligament stem cells and antimicrobial activity in vitro and increased osseointegration in a rodent animal model 4 wk postsurgery as compared with untreated implants. Altogether, our in vitro and in vivo studies suggest that this approach can be extended to other dental and orthopedic implants since this surface functionalization showed improved osseointegration and an enhanced success rate.
Topics: Animals; Anti-Bacterial Agents; Coated Materials, Biocompatible; Dental Implants; Osseointegration; Osteogenesis; Surface Properties; Titanium
PubMed: 34315313
DOI: 10.1177/00220345211029185 -
Clinical Oral Investigations Apr 2022To evaluate re-osseointegration after electrolytic cleaning and regenerative therapy of dental implants with peri-implantitis in humans.
OBJECTIVE
To evaluate re-osseointegration after electrolytic cleaning and regenerative therapy of dental implants with peri-implantitis in humans.
MATERIAL AND METHODS
Four dental implants that developed peri-implantitis underwent electrolytic cleaning followed by regenerative therapy with guided bone regeneration. All four implants developed recurrent peri-implantitis and were therefore explanted 6 to 13 months later. Radiographic bone level, probing depth, and bleeding on probing were determined at the time of surgery, 6 months later, and before implant retrieval. The peri-implant tissues were histologically and histomorphometrically analyzed.
RESULTS
All four implants demonstrated radiographic and histological bone gain, reduced probing depth, and bleeding on probing. Radiographic bone gain was 5.8 mm mesially and 4.8 mm distally for implant #1, 3.3 mm and 2.3 mm for implant #2, 3.1 mm and 0.5 mm for implant #3, and 3.5 mm and 2.8 mm for implant #4. The histometric mean and maximum vertical bone gain for implant #1 to #4 was 1.65 mm and 2.54 mm, 3.04 mm and 3.47 mm, 0.43 mm and 1.27 mm, and 4.16 mm and 5.22 mm, respectively. The percentage of re-osseointegration for implant #1 to #4 was 21.0%, 36.9%, 5.7%, and 39.0%, respectively. In one implant, the newly formed bone was deposited directly onto calculus on the implant surface.
CONCLUSIONS
We found that (1) re-osseointegration is possible on a formerly contaminated implant surface and (2) the electrolytic cleaning process seems to be effective enough at sites with calculus residues.
CLINICAL RELEVANCE
Since re-osseointegration can be achieved by electrolytic cleaning, this decontamination technique may be considered as a future treatment concept.
Topics: Bone Regeneration; Dental Implants; Humans; Osseointegration; Peri-Implantitis
PubMed: 35244779
DOI: 10.1007/s00784-021-04345-1