Dataset Information

Titanium Implant Surface Effects on Adherent Macrophage Phenotype: A Systematic Review.

ABSTRACT: Immunomodulatory biomaterials have the potential to stimulate an immune response able to promote constructive and functional tissue remodeling responses as opposed to persistent inflammation and scar tissue formation. As such, the controlled activation of macrophages and modulation of their phenotype through implant surface modification has emerged as a key therapeutic strategy.

Methods

Online databases were searched for in vitro studies between January 1991 and June 2020 which examined the effect of titanium implant surface topography on the adherent macrophage phenotype at either the gene or protein level.

Results

Thirty-nine studies were subsequently included for review. Although there was significant heterogeneity between studies, treatment of titanium surfaces increased the surface roughness or hydrophilicity, and hence increased macrophage attachment but decreased cell spreading. Physical coating of the titanium surface also tended to promote the formation of cell clusters. Titanium and titanium-zirconium alloy with a micro- or nano-scale rough topography combined with a hydrophilic surface chemistry were the most effective surfaces for inducing an anti-inflammatory phenotype in adherent macrophages, as indicated by significant changes in cytokine gene expression and or cytokine secretion profiles.

Conclusions

The published data support the hypothesis that incorporation of specific topographical and physiochemical surface modifications to titanium can modulate the phenotypic response of adherent macrophages.

SUBMITTER: Pitchai M

PROVIDER: S-EPMC9609829 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Titanium Implant Surface Effects on Adherent Macrophage Phenotype: A Systematic Review.

Pitchai Manju M Ipe Deepak D Tadakamadla Santosh S Hamlet Stephen S

Materials (Basel, Switzerland) 20221019 20

Immunomodulatory biomaterials have the potential to stimulate an immune response able to promote constructive and functional tissue remodeling responses as opposed to persistent inflammation and scar tissue formation. As such, the controlled activation of macrophages and modulation of their phenotype through implant surface modification has emerged as a key therapeutic strategy.<h4>Methods</h4>Online databases were searched for in vitro studies between January 1991 and June 2020 which examined t ...[more]

PMID: 36295379

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Project description:Metabolic bone is highly innervated by both sensory and sympathetic nerves. In addition to skeletal development, neural regulation participates in local bone remodeling, which is important for successful osseointegration of titanium implants. Neurectomy is a model used to investigate the lack of neural function on bone homeostasis, but the relative impacts of direct denervation to bone or denervation-induced muscle paralysis are less well defined. To investigate this difference, we used two nerve intervention models, sciatic and femoral neurectomy (SFN) v. botox-induced muscle paralysis (BTX) and assessed the resulting femoral bone phenotype and Ti implant osseointegration. Male Sprague Dawley rats (19) were randomly divided into three groups: implant control (n = 5), SFN (n = 7), and BTX (n = 7). Ti implants (microrough/hydrophilic [modSLA], Institut Straumann AG) were placed in the distal metaphysis of each femur on day 24 post-SFN or BTX. Bone and muscle were examined on day 28 after implant insertion. Both nerve intervention models impaired osseointegration. MicroCT and histology indicated that both models had reduced trabecular bone formation. Only BTX reduced cortical bone formation and increased cortical bone porosity. BTX resulted in more bone loss characterized by the least trabecular and cortical bone, as well as osseointegration. Osteoblasts isolated from the tibia exhibited a model-specific phenotype when they were grown on Ti substrates in vitro. Neurectomy caused more severe muscle atrophy than botox injection. These results indicate that neural regulation directly modulates bone formation and osseointegration. Muscle paralysis modulated the effects of loss of neural inputs into bone, supporting the hypothesis that mechanical loading of bone is a factor in achieving successful osseointegration. The different effects of botox and neurectomy on bone phenotype indicated that the sensory and sympathetic nerves had a role in the osseointegration process.

Project description:Osseointegration at the bone-implant interface is a complex biological process that is triggered by the immune-inflammatory response and mediated by various cell types such as, bone-forming cells and immune cells, especially macrophages. The polarization of macrophages to inflammatory/regenerative (M1/M2) phenotypes, as well as the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) at the bone-implant interface, significantly affects implant osseointegration and even causes implant failure. Graphene oxide (GO) is a promising candidate for performing implant surface functionalization to modulate the interactions between implants and cells. Herein, we explored the effects of a GO coating on the osteogenic differentiation of BMSCs and the polarization of macrophages to enhance the application of GO surface modification in improving bone-implant integration. In the present study, a large particle sandblasting and acid etching (SLA) surface that is commonly used in clinical practice was selected as the control group, and GO was deposited on the SLA surface by the ultrasonic atomization spraying technique. The surface characteristics of these two groups, including the surface morphology, roughness, wettability, protein adsorption capacity and cell compatibility, were assessed. Then, the effects of GO surface modification on the osteogenic differentiation of BMSCs and the polarization of macrophages were evaluated. The results showed that the GO coating was successfully fabricated on the titanium substrates, which endowed the SLA surface with improved hydrophilicity and protein adsorption capacity and reduced roughness. Compared with the SLA surface, the GO-modified surface significantly enhanced the osteogenic differentiation of BMSCs and the M2-phenotype polarization of macrophages in vitro. This dual-regulatory role is of great significance in achieving rapid osseointegration as well as resolving the poor osseointegration associated with macrophage-related inflammation.

Project description:A critical stage during osseointegration of a titanium (Ti) implant is primary bone remodeling, which involves cross talk among osteoclast precursors, osteoclasts, mesenchymal stem cells (MSCs), and osteoblasts. This phase couples the processes of bone formation and resorption. During remodeling, osteoclasts produce factors capable of regulating MSC migration and osteogenesis. Furthermore, they degrade primary bone, creating a foundation with a specific chemistry, stiffness, and morphology for osteoblasts to synthesize and calcify their matrix. MSCs and osteoblasts receiving cues from the implant surface produce factors capable of regulating osteoclasts in order to promote net new bone formation. The purpose of this study was to determine the effects Ti implant surfaces have on bone remodeling. Human MSCs and normal human osteoblasts (NHOsts) were cultured separately on 15 mm grade 2 smooth PT, hydrophobic-microrough SLA, hydrophilic-microrough Ti (mSLA) (Institut Straumann AG, Basel, Switzerland), or tissue culture polystyrene (TCPS). After 7d, conditioned media from surface cultures were used to treat human osteoclasts for 2d. Activity was measured by fluorescence of released collagen followed by mRNA quantification. This study demonstrates that MSC and NHOst cultures are able to suppress osteoclast activity in a surface dependent manner and osteoclast mRNA levels are selectively regulated by surface treatments. The substrate-dependent regulatory effect was mitigated when MSCs were silenced for integrin subunits and when conditioned media were denatured. These results indicate that MSCs and NHOsts regulate at least two aspects of remodeling: reduced fusion of new osteoclasts and reduced activity of existing osteoclasts.Statement of significanceIn this study, we developed a novel in vitro model to study how microstructured and hydrophilic titanium implants impact bone remodeling for dental and orthopaedic applications. Our approach intersects biomaterials and systems physiology, revealing for the first time that implant surface properties are capable of regulating the communication among the cells involved in remodeling of primary bone during osseointegration. We believe that the basic research presented in our manuscript will provide important knowledge in our understanding of factors that impact implant success. Furthermore, it provides a solid foundation for the development of materials that enable rapid osseointegration and earlier loading times for implants in bone that has been compromised by trauma or disease.

Dataset Information

Titanium Implant Surface Effects on Adherent Macrophage Phenotype: A Systematic Review.

Methods

Results

Conclusions

Publications

Titanium Implant Surface Effects on Adherent Macrophage Phenotype: A Systematic Review.

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