Insights into Surface Treatment Methods of Titanium Dental Implants

Titanium is the most widely used material for dental implants, due to its desirable properties, e.g., high biocompatibility, low density, high stiffness and strength, etc. More importantly, titanium implants may osseointegrate with living bone, meaning that new bone grows directly onto the surface of the implant, without any intermediate soft tissue layer. A successfully osseointegrated implant generally has a strong bonding to the adjacent bone; consequently, it usually functions well and remains stable for long service period. It also has been clinically proven that surface treatment methods can improve the rate and quality of titanium implants' osseointegration. This article focuses on two such methods, i.e., surface roughening and hydroxyapatite (HA) coating. In addition, we discuss a promising new methodology, which attempts to modify the surface charge of titanium materials. This paper focuses on the current best surface treatment methods for titanium dental implants developed and improved in the past two decades, i.e., 1990–2010.     

Direct observation of bone coherence with dental implants

A newly developed gentle ion beam polishing technique was established for preparing of cross sections of dental implants feasible for high resolution scanning electron microscope investigation. This approach was applied to investigate the interfacial microstructure between newly formed bone and dental implants with modified surfaces extracted after in vivo test in adult miniature pigs. The results obtained so far reveal that it has become possible to analyze the bone coherence to implants besides measuring the bone coverage. The amount and density of the mineralized extra cellular matrix has found to be different in different sub-microscopic regions around the implant. From our observations, it can be seen that new bone grows from the existing bone and advances towards the implant surface by in growth mechanism. The images also reveal that new bone is formed directly at the implant surface; we propose a deposition mechanism to explain this. Eventually the in grown and the deposited bone connect to give a good anchorage of the implant. This achievement bears implication for understanding osseointegration at microscopic level.     

Addition of Adipose-Derived Stem Cells to Mesenchymal Stem Cell Sheets Improves Bone Formation at an Ectopic Site

To determine the effect of adipose-derived stem cells (ADSCs) added to bone marrow-derived mesenchymal stem cell (MSC) sheets on bone formation at an ectopic site. We isolated MSCs and ADSCs from the same rabbits. We then prepared MSC sheets for implantation with or without ADSCs subcutaneously in the backs of severe combined immunodeficiency (SCID) mice. We assessed bone formation at eight weeks after implantation by micro-computed tomography and histological analysis. In osteogenic medium, MSCs grew to form multilayer sheets containing many calcium nodules. MSC sheets without ADSCs formed bone-like tissue; although neo-bone and cartilage-like tissues were sparse and unevenly distributed by eight weeks after implantation. In comparison, MSC sheets with ADSCs promoted better bone regeneration as evidenced by the greater density of bone, increased mineral deposition, obvious formation of blood vessels, large number of interconnected ossified trabeculae and woven bone structures, and greater bone volume/total volume within the composite constructs. Our results indicate that although sheets of only MSCs have the potential to form tissue engineered bone at an ectopic site, the addition of ADSCs can significantly increase the osteogenic potential of MSC sheets. Thus, the combination of MSC sheets with ADSCs may be regarded as a promising therapeutic strategy to stimulate bone regeneration.     

Early Fixation of Cobalt-Chromium Based Alloy Surgical Implants to Bone Using a Tissue-engineering Approach

To establish the methods of demonstrating early fixation of metal implants to bone, one side of a Cobalt-Chromium (CoCr) based alloy implant surface was seeded with rabbit marrow mesenchymal cells and the other side was left unseeded. The mesenchymal cells were further cultured in the presence of ascorbic acid, β-glycerophosphate and dexamethasone, resulting in the appearance of osteoblasts and bone matrix on the implant surface. Thus, we succeeded in generating tissue-engineered bone on one side of the CoCr implant. The CoCr implants were then implanted in rabbit bone defects. Three weeks after the implantation, evaluations of mechanical test, undecalcified histological section and electron microscope analysis were performed. Histological and electron microscope images of the tissue engineered surface exhibited abundant new bone formation. However, newly formed bone tissue was difficult to detect on the side without cell seeding. In the mechanical test, the mean values of pull-out forces were 77.15 N and 44.94 N for the tissue-engineered and non-cell-seeded surfaces, respectively. These findings indicate early bone fixation of the tissue-engineered CoCr surface just three weeks after implantation.     

Preclinical study probing primary stability of dental implants in synthetic and natural bones

The natural bone is a biological example of a polymer–ceramic composite with a higher volume fraction of nanosized ceramic (around 65% hydroxyapatite) dispersed in polymer (collagenous) matrix. The loading of a dental implant involves the biomechanical interactions of the implant with such natural composites in the jaw bones of human subjects. In particular, the insertion torque responses of the dental implant are related to the implant design, in particular the external thread morphology, which influences the primary stability of the implant. In this study, the effect of the bone properties (polyurethane-based synthetic bone, porcine and human cadaver lumbar bone) and clinically relevant implant driving protocols on the insertion and removal torques of newly designed implant variants (hybrid threads with macro- and micro-threads) were assessed, quantitatively and qualitatively. It was observed that torque response increased with an increase in bone density, irrespective of the implant designs. The torque response of the implants in both synthetic and natural bones was benchmarked with the commercially available implant. The implants with bone cutting partial macro-threads at the apical end without inter thread gap exhibited comparable clinically relevant results with respect to control implants and were found to be most suitable for implantation into natural bone.     

Biomechanical Evaluation of Ti-Nb-Sn Alloy Implants with a Low Young’s Modulus

Dental implants are widely used and are a predictable treatment in various edentulous cases. Occlusal overload may be causally related to implant bone loss and a loss of integration. Stress concentrations may be diminished using a mechanobiologically integrated implant with bone tissue. The purpose of this study was to investigate the biomechanical behavior, biocompatibility and bioactivity of a Ti-Nb-Sn alloy as a dental implant material. It was compared with cpTi. Cell proliferation and alkaline phosphatase (ALP) activity were quantified. To assess the degree of osseointegration, a push-in test was carried out. Cell proliferation and ALP activity in the cells grown on prepared surfaces were similar for the Ti-Nb-Sn alloy and for cpTi in all the experiments. A comparison between the Ti-Nb-Sn alloy implant and the cpTi implant revealed that no significant difference was apparent for the push-in test values. These results suggest that implants fabricated using Ti-Nb-Sn have a similar biological potential as cpTi and are capable of excellent osseointegration.     

A novel effect of sandblasting on titanium surface: static charge generation

Recent advances in biomaterials’ research suggest that electrical charges on a dental implant surface significantly improve its osseointegration to living bone, as a result of selective osteoblast activation and fibroblast inhibition. This study aims at investigating the possibility of using sandblasting to modify the electrical charges on the surface of titanium materials. Our experiments used Al₂O₃ grits to blast on CP2 titanium plates, for durations between 3 and 30?s. After sandblasting, Ti surfaces were measured for their electrostatic voltage. The results indicate a novel finding, i.e. negative static charges are generated on the titanium surface, which may stimulate osteoblast activity to promote osseointegration around dental implant surface. This finding may at least partially explain the good osseointegration results of sandblasted titanium dental implants, in addition to other known reasons, such as topological changes on the implant’s surface. However, the static charges accumulated on the titanium surface during sandblasting decayed to a lower level with time. It remains a challenging task to seek ways to retain these charges after quantification of desired level of negative charges needed to promote osteoblast activity for osseointegration around dental implants.     

Biohybrid Bovine Bone Matrix for Controlled Release of Mesenchymal Stem/Stromal Cell Lyosecretome: A Device for Bone Regeneration

SmartBone^® (SB) is a biohybrid bone substitute advantageously proposed as a class III medical device for bone regeneration in reconstructive surgeries (oral, maxillofacial, orthopedic, and oncology). In the present study, a new strategy to improve SB osteoinductivity was developed. SB scaffolds were loaded with lyosecretome, a freeze-dried formulation of mesenchymal stem cell (MSC)-secretome, containing proteins and extracellular vesicles (EVs). Lyosecretome-loaded SB scaffolds (SBlyo) were prepared using an absorption method. A burst release of proteins and EVs (38% and 50% after 30 min, respectively) was observed, and then proteins were released more slowly with respect to EVs, most likely because they more strongly adsorbed onto the SB surface. In vitro tests were conducted using adipose tissue-derived stromal vascular fraction (SVF) plated on SB or SBlyo. After 14 days, significant cell proliferation improvement was observed on SBlyo with respect to SB, where cells filled the cavities between the native trabeculae. On SB, on the other hand, the process was still present, but tissue formation was less organized at 60 days. On both scaffolds, cells differentiated into osteoblasts and were able to mineralize after 60 days. Nonetheless, SBlyo showed a higher expression of osteoblast markers and a higher quantity of newly formed trabeculae than SB alone. The quantification analysis of the newly formed mineralized tissue and the immunohistochemical studies demonstrated that SBlyo induces bone formation more effectively. This osteoinductive effect is likely due to the osteogenic factors present in the lyosecretome, such as fibronectin, alpha-2-macroglobulin, apolipoprotein A, and TGF-β.     

Freeze-Dried Secretome (Lyosecretome) from Mesenchymal Stem/Stromal Cells Promotes the Osteoinductive and Osteoconductive Properties of Titanium Cages

Titanium is one of the most frequently used materials in bone regeneration due to its good biocompatibility, excellent mechanical properties, and great osteogenic performance. However, osseointegration with host tissue is often not definite, which may cause implant failure at times. The present study investigates the capacity of the mesenchymal stem cell (MSC)-secretome, formulated as a ready-to-use and freeze-dried medicinal product (the Lyosecretome), to promote the osteoinductive and osteoconductive properties of titanium cages. In vitro tests were conducted using adipose tissue-derived MSCs seeded on titanium cages with or without Lyosecretome. After 14 days, in the presence of Lyosecretome, significant cell proliferation improvement was observed. Scanning electron microscopy revealed the cytocompatibility of titanium cages: the seeded MSCs showed a spread morphology and an initial formation of filopodia. After 7 days, in the presence of Lyosecretome, more frequent and complex cellular processes forming bridges across the porous surface of the scaffold were revealed. Also, after 14 and 28 days of culturing in osteogenic medium, the amount of mineralized matrix detected by alizarin red was significantly higher when Lyosecretome was used. Finally, improved osteogenesis with Lyosecretome was confirmed by confocal analysis after 28 and 56 days of treatment, and demonstrating the production by osteoblast-differentiated MSCs of osteocalcin, a specific bone matrix protein.     

Effect of Plasma Treatment on Titanium Surface on the Tissue Surrounding Implant Material

Early osseointegration is important to achieve initial stability after implant placement. We have previously reported that atmospheric-pressure plasma treatment confers superhydrophilicity to titanium. Herein, we examined the effects of titanium implant material, which was conferred superhydrophilicity by atmospheric-pressure plasma treatment, on the surrounding tissue in rat femur. Control and experimental groups included untreated screws and those irradiated with atmospheric-pressure plasma using piezobrush, respectively. The femurs of 8-week-old male Sprague-Dawley rats were used for in vivo experiments. Various data prepared from the Micro-CT analysis showed results showing that more new bone was formed in the test group than in the control group. Similar results were shown in histological analysis. Thus, titanium screw, treated with atmospheric-pressure plasma, could induce high hard tissue differentiation even at the in vivo level. This method may be useful to achieve initial stability after implant placement.     

Recombinant human bone morphogenetic protein-2 loaded porous β-tricalcium phosphate microsphere-hyaluronic acid composites promoted osseointegration around titanium implants

We fabricated two β-tricalcium phosphates (β-TCP) microsphere-hyaluronic acid composites and evaluate their efficacy as recombinant human bone morphogenetic protein-2 (rhBMP-2) carriers when combined with titanium implants in rabbit tibial diaphysis. After 4 weeks, the new bone formation was observed with plain radiographs and histology and was analyzed via micro-CT. Micro-CT analyses results showed the composites with hydrogel and BMP had a significantly higher bone to implant contact ratios and new bone formation than the other groups did. Our results indicated that rhBMP-2 loaded β-TCP/hydrogel composites could significantly elevate osteogenesis and osseointegration of the titanium implants in rabbit tibia medullary space.     

Osseointegration of Sandblasted and Acid-Etched Implant Surfaces. A Histological and Histomorphometric Study in the Rabbit

Titanium surface is an important factor in achieving osseointegration during the early wound healing of dental implants in alveolar bone. The purpose of this study was to evaluate sandblasted-etched surface implants to investigate the osseointegration. In the present study, we used two different types of sandblasted-etched surface implants, an SLA™ surface and a Nanoblast Plus™ surface. Roughness and chemical composition were evaluated by a white light interferometer microscope and X-ray photoelectron spectroscopy, respectively. The SLA™ surface exhibited the higher values (Ra 3.05 μm) of rugosity compared to the Nanoblast Plus™ surface (Ra 1.78 μm). Both types of implants were inserted in the femoral condyles of ten New Zealand white rabbits. After 12 weeks, histological and histomorphometric analysis was performed. All the implants were osseointegrated and no signs of infection were observed. Histomorphometric analysis revealed that the bone–implant contact % (BIC) ratio was similar around the SLA™ implants (63.74 ± 13.61) than around the Nanoblast Plus™ implants (62.83 ± 9.91). Both implant surfaces demonstrated a favorable bone response, confirming the relevance of the sandblasted-etched surface on implant osseointegration.     

Early Bone Healing on Hydroxyapatite-Coated and Chemically-Modified Hydrophilic Implant Surfaces in an Ovine Model

Implant topography affects early peri-implant bone healing by changing the osteoconduction rate in the surrounding biological environment. Implant surfaces have been designed to promote faster and stronger bone formation for rapid and stable prosthesis loading. Early peri-implant bone healing has been observed with a sandblasted, acid-etched implant that was chemically modified to be hydrophilic (cmSLA). The present study investigates whether early peri-implant bone healing extends to a rough surface implant with a high crystalline hydroxyapatite surface (TSV MP-1 HA). Three implants were randomly placed in porous trabecular bone within both medial femoral condyles of 10 sheep. Early peri-implant bone stability was measured at 3- and 6-weeks healing time following implant insertion. Results indicated a similar implant stability quotient between the implants at insertion and over time. The significant increase over time of reverse torque values with respect to insertion torque (p < 0.001) did not differ between the implants. However, the bone-to-implant contact of TSV MP-1 HA was significantly higher than that of cmSLA implants at 6 weeks (p < 0.01). These data validate previous findings of a hydrophilic implant surface and extend the observation of early osseointegration to a rough surface implant in porous trabecular bone.     

Healing Pattern Analysis for Dental Implants Using the Mechano-Regulatory Tissue Differentiation Model

(1) Background: Our aim is to reveal the influence of the geometry designs on biophysical stimuli and healing patterns. The design guidelines for dental implants can then be provided. (2) Methods: A two-dimensional axisymmetric finite element model was developed based on mechano-regulatory algorithm. The history of tissue differentiation around eight selected implants can be predicted. The performance of the implants was evaluated by bone area (BA), bone-implant contact (BIC); (3) Results: The predicted healing patterns have very good agreement with the experimental observation. Many features observed in literature, such as soft tissues covering on the bone-implant interface; crestal bone loss; the location of bone resorption bumps, were reproduced by the model and explained by analyzing the solid and fluid biophysical stimuli and (4) Conclusions: The results suggested the suitable depth, the steeper slope of the upper flanks, and flat roots of healing chambers can improve the bone ingrowth and osseointegration. The mechanism related to solid and fluid biophysical stimuli were revealed. In addition, the model developed here is efficient, accurate and ready to extend to any geometry of dental implants. It has potential to be used as a clinical application for instant prediction/evaluation of the performance of dental implants.     

含锌磷酸钙生物材料的研究进展

在钙磷酸盐基础上设计生物活性材料有望发展出高性能临床应用的硬组织修复材料。含锌钙磷酸盐材料能刺激骨组织生长,成为研究的热点。综述了含锌的钙磷酸盐材料研究状况,着重讨论钙磷酸盐材料中锌离子的存在状态以及掺锌后的物理化学性能,包括:含锌钙磷酸盐材料的合成和性能,锌的生物学性能以及含锌钙磷酸盐材料在体内和体外的研究状况。这些对于含锌钙磷酸盐材料植入后促进骨形成具有重要的影响。     

Ultrasonographic and Histological Correlation after Experimental Reconstruction of a Volumetric Muscle Loss Injury with Adipose Tissue

Different types of scaffolds are used to reconstruct muscle volume loss injuries. In this experimental study, we correlated ultrasound observations with histological findings in a muscle volume loss injury reconstructed with autologous adipose tissue. The outcome is compared with decellularized and porous matrix implants. Autologous adipose tissue, decellularized matrix, and a porous collagen matrix were implanted in volumetric muscle loss (VML) injuries generated on the anterior tibial muscles of Wistar rats. Sixty days after implantation, ultrasound findings were compared with histological and histomorphometric analysis. The muscles with an autologous adipose tissue implant exhibited an ultrasound pattern that was quite similar to that of the regenerative control muscles. From a histological point of view, the defects had been occupied by newly formed muscle tissue with certain structural abnormalities that would explain the differences between the ultrasound patterns of the normal control muscles and the regenerated ones. While the decellularized muscle matrix implant resulted in fibrosis and an inflammatory response, the porous collagen matrix implant was replaced by regenerative muscle fibers with neurogenic atrophy and fibrosis. In both cases, the ultrasound images reflected echogenic, echotextural, and vascular changes compatible with the histological findings of failed muscle regeneration. The ultrasound analysis confirmed the histological findings observed in the VML injuries reconstructed by autologous adipose tissue implantation. Ultrasound can be a useful tool for evaluating the structure of muscles reconstructed through tissue engineering.     

Bioactivity of hydroxyapatite/wollastonite composite films deposited by pulsed laser

Hydroxyapatite/wollastonite (HA/WS) composite films on titanium alloy were prepared by pulsed laser deposition, and their bioactivity was studied. The dissolution and precipitation behaviors of the films were evaluated by soaking in simulated body fluid (SBF), and the osseointegration ability was evaluated by in vivo test. In the early soaking stage, the dissolution action will dominate, thus resulting in the gradual disappearance of the smooth spherical feature of the particles. After 7 days of soaking, new precipitates were observed which indicates that reprecipitation reaction dominates, and the surface was almost completely covered by new precipitates after the film was soaked for 28 days. The in vivo test showed that the composite films have excellent osseointegration ability. When the sample was embedded in the shin bone of rabbit for 3 weeks, a good combination of bone tissue and implant was achieved, and after embedding for 6 weeks, osteoblasts were observed between the bone tissue and implant.     

Morphology,Composition, and Bioactivity of Strontium-Doped Brushite Coatings Deposited on Titanium Implants via Electrochemical Deposition

Surface modification techniques have been applied to generate titanium implant surfaces that promote osseointegration for use in dental applications. In this study, strontium-doped brushite coatings were deposited on titanium by electrochemical deposition. The phase composition of the coating was investigated by energy dispersive X-ray spectroscopy and X-ray diffraction. The surface morphologies of the coatings were studied through scanning electron microscopy, and the cytocompatibility and bioactivity of the strontium-doped brushite coatings were evaluated using cultured osteoblasts. Osteoblast proliferation was enhanced by the addition of strontium, suggesting a possible mechanism by which strontium incorporation in brushite coatings increased bone formation surrounding the implants. Cell growth was also strongly influenced by the composition of the deposited coatings, with a 10% Sr-doped brushite coating inducing the greatest amount of bone formation among the tested materials.     

The Body’s Cellular and Molecular Response to Protein-Coated Medical Device Implants: A Review Focused on Fibronectin and BMP Proteins

Recent years have seen a marked rise in implantation into the body of a great variety of devices: hip, knee, and shoulder replacements, pacemakers, meshes, glucose sensors, and many others. Cochlear and retinal implants are being developed to restore hearing and sight. After surgery to implant a device, adjacent cells interact with the implant and release molecular signals that result in attraction, infiltration of the tissue, and attachment to the implant of various cell types including monocytes, macrophages, and platelets. These cells release additional signaling molecules (chemokines and cytokines) that recruit tissue repair cells to the device site. Some implants fail and require additional revision surgery that is traumatic for the patient and expensive for the payer. This review examines the literature for evidence to support the possibility that fibronectins and BMPs could be coated on the implants as part of the manufacturing process so that the proteins could be released into the tissue surrounding the implant and improve the rate of successful implantation.     

In Vitro and In Vivo Characterization of PLLA-316L Stainless Steel Electromechanical Devices for Bone Tissue Engineering—A Preliminary Study

Bone injuries represent a major social and financial impairment, commonly requiring surgical intervention due to a limited healing capacity of the tissue, particularly regarding critical-sized defects and non-union fractures. Regenerative medicine with the application of bone implants has been developing in the past decades towards the manufacturing of appropriate devices. This work intended to evaluate medical 316L stainless steel (SS)-based devices covered by a polymer poly (L-lactic acid) (PLLA) coating for bone lesion mechanical and functional support. SS316L devices were subjected to a previously described silanization process, following a three-layer PLLA film coating. Devices were further characterized and evaluated towards their cytocompatibility and osteogenic potential using human dental pulp stem cells, and biocompatibility via subcutaneous implantation in a rat animal model. Results demonstrated PLLA-SS316L devices to present superior in vitro and in vivo outcomes and suggested the PLLA coating to provide osteo-inductive properties to the device. Overall, this work represents a preliminary study on PLLA-SS316L devices’ potential towards bone tissue regenerative techniques, showing promising outcomes for bone lesion support.