-
Advanced Healthcare Materials Jan 2024Implantable biomaterials are widely used in bone tissue engineering, but little is still known about how they initiate early immune recognition and the initial dynamics....
Implantable biomaterials are widely used in bone tissue engineering, but little is still known about how they initiate early immune recognition and the initial dynamics. Herein, the early immune recognition and subsequent osteoinduction of biphasic calcium phosphate (BCP) after implantation to the protein adsorption behavior is attributed. By liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis, the biomaterial-related molecular patterns (BAMPs) formed after BCP implantation are mapped, dominated by the highly expressed extracellular matrix protein fibronectin (Fn) and the high mobility group box 1 (HMGB1). Molecular dynamics simulations show that Fn has the ability to bind more readily to the BCP surface than HMGB1. The preferential binding of Fn provides a higher adsorption energy for HMGB1. Furthermore, multiple hydrogen bonding sites between HMGB1 and Fn are demonstrated using a molecular docking approach. Ultimately, the formation of BAMPs through HMGB1 antagonist glycyrrhizic acid (GA), resulting in impaired immune recognition of myeloid differentiation factor 88 (MYD88) mediated dendritic cells (DCs) and macrophages (Mφs), as well as failed osteoinduction processes is obstructed. This study introduces a mechanism for early immune recognition of implant materials based on protein adsorption, providing perspectives for future design and application of tissue engineering materials.
Topics: Biocompatible Materials; Fibronectins; HMGB1 Protein; Adsorption; Chromatography, Liquid; Molecular Docking Simulation; Tandem Mass Spectrometry; Hydroxyapatites
PubMed: 37602504
DOI: 10.1002/adhm.202301808 -
Langmuir : the ACS Journal of Surfaces... Jan 2024Osteocalcin is the most abundant noncollagenous bone protein and the functions in bone remineralization as well as in inhibition of bone growth have remained unclear. In...
Osteocalcin is the most abundant noncollagenous bone protein and the functions in bone remineralization as well as in inhibition of bone growth have remained unclear. In this contribution, we explain the dual role of osteocalcin in the nucleation of new calcium phosphate during bone remodeling and in the inhibition of hydroxyapatite crystal growth at the molecular scale. The mechanism was derived using pH-resolved all-atom models for the protein, phosphate species, and hydroxyapatite, along with molecular dynamics simulations and experimental and clinical observations. Osteocalcin binds to () hydroxyapatite surfaces through multiple residues, identified in this work, and the fingerprint of binding residues varies as a function of the () crystal facet and pH value. On balance, the affinity of osteocalcin to hydroxyapatite slows down crystal growth. The unique tricalcium γ-carboxylglutamic acid (Gla) domain hereby rarely adsorbs to hydroxyapatite surfaces and faces instead toward the solution. The Gla domain enables prenucleation of calcium phosphate for new bone formation at a slightly acidic pH of 5. The growth of prenucleation clusters of calcium phosphate continues upon increase in pH value from 5 to 7 and is much less favorable, or not observed, on the native osteocalcin structure at and above neutral pH values of 7. The results provide mechanistic insight into the early stages of bone remodeling from the molecular scale, help inform mutations of osteocalcin to modify binding to apatites, support drug design, and guide toward potential cures for osteoporosis and hyperosteogeny.
Topics: Osteocalcin; Durapatite; Bone and Bones; Calcium Phosphates
PubMed: 38181199
DOI: 10.1021/acs.langmuir.3c02948 -
Zhongguo Xiu Fu Chong Jian Wai Ke Za... Sep 2023To investigate the preparation and properties of the novel silica (SiO )/hydroxyapatite (HAP) whiskers porous ceramics scaffold.
OBJECTIVE
To investigate the preparation and properties of the novel silica (SiO )/hydroxyapatite (HAP) whiskers porous ceramics scaffold.
METHODS
The HAP whiskers were modified by the SiO microspheres using the Stöber method. Three types of SiO /HAP whiskers were fabricated under different factors (for the No.1 samples, the content of tetraethoxysilane, stirring time, calcination temperature, and soaking time were 10 mL, 12 hours, 560℃, and 0.5 hours, respectively; and in the No.2 samples, those were 15 mL, 24 hours, 650℃, and 2 hours, respectively; while those in the No.3 samples were 20 mL, 48 hours, 750℃, and 4 hours, respectively). The phase and morphology of the self-made HAP whisker and 3 types of SiO /HAP whiskers were detected by the X-ray diffraction analysis and scanning electron microscopy. Taken the self-made HAP whisker and 3 types of SiO /HAP whiskers as raw materials, various porous ceramic materials were prepared using the mechanical foaming method combined with extrusion molding method, and the low-temperature heat treatment. The pore structure of porous ceramics was observed by scanning electron microscopy. Its porosity and pore size distribution were measured. And further the axial compressive strength was measured, and the biodegradability was detected by simulated body fluid. Cell counting kit 8 method was used to conduct cytotoxicity experiments on the extract of porous ceramics.
RESULTS
The SiO microspheres modified HAP whiskers and its porous ceramic materials were prepared successfully, respectively. In the SiO /HAP whiskers, the amorphous SiO microspheres with a diameter of 200 nm, uniform distribution and good adhesion were attached to the surface of the whiskers, and the number of microspheres was controllable. The apparent porosity of the porous ceramic scaffold was about 78%, and its pore structure was composed of neatly arranged longitudinal through-holes and a large number of micro/nano through-holes. Compared with HAP whisker porous ceramic, the axial compressive strength of the SiO /HAP whisker porous ceramics could reach 1.0 MPa, which increased the strength by nearly 4 times. Among them, the axial compressive strength of the No.2 SiO /HAP whisker porous ceramic was the highest. The SiO microspheres attached to the surface of the whiskers could provide sites for the deposition of apatite. With the content of SiO microspheres increased, the deposition rate of apatite accelerated. The cytotoxicity level of the prepared porous ceramics ranged from 0 to 1, without cytotoxicity.
CONCLUSION
SiO /HAP whisker porous ceramics have good biological activity, high porosity, three-dimensional complex pore structure, good axial compressive strength, and no cytotoxicity, which make it a promising scaffold material for bone tissue engineering.
Topics: Animals; Durapatite; Porosity; Vibrissae; Apatites; Ceramics; Silicon Dioxide
PubMed: 37718429
DOI: 10.7507/1002-1892.202304073 -
Journal of Materials Chemistry. B Mar 2024Due to limitations of biological and alloplastic grafts, regenerative engineering has emerged as a promising alternative to treat bone defects. Bioactive polymeric... (Review)
Review
Due to limitations of biological and alloplastic grafts, regenerative engineering has emerged as a promising alternative to treat bone defects. Bioactive polymeric scaffolds are an integral part of such an approach. Bioactivity importantly induces hydroxyapatite mineralization that promotes osteoinductivity and osseointegration with surrounding bone tissue. Strategies to confer bioactivity to polymeric scaffolds utilize bioceramic fillers, coatings and surface treatments, and additives. These approaches can also favorably impact mechanical and degradation properties. A variety of fabrication methods are utilized to prepare scaffolds with requisite morphological features. The bioactivity of scaffolds may be evaluated with a broad set of techniques, including (acellular and cellular) and methods. Herein, we highlight contemporary and emerging approaches to prepare and assess scaffold bioactivity, as well as existing challenges.
Topics: Tissue Scaffolds; Polymers; Bone and Bones; Durapatite
PubMed: 38410921
DOI: 10.1039/d3tb02674d -
Journal of the Mechanical Behavior of... Aug 2023Tissue engineering is a continuously evolving field. One of the main lines of research in this field focuses on the replacement of bone defects with materials designed...
Tissue engineering is a continuously evolving field. One of the main lines of research in this field focuses on the replacement of bone defects with materials designed to interact with the cells of a living organism in order to provide the body with a structure on which new tissues can easily grow. Among the most commonly used materials are bioglasses, which are frequently used due to their versatility and good properties. This article discusses the results of the production of an injectable paste of Bioglass® 45S5 and hydroxyapatite on a 3D printed porous structure by additive manufacturing, using a thermoplastic (PLA). The results were evaluated in a specific application of the paste, so the mechanical and bioactive properties were studied to show the multiple possibilities of using this combination for its application in regenerative medicine and more specifically in bone implants.
Topics: Tissue Scaffolds; Durapatite; Tissue Engineering; Ceramics
PubMed: 37307642
DOI: 10.1016/j.jmbbm.2023.105937 -
Dermatologic Clinics Jan 2024Hyaluronic acid and calcium hydroxylapatite (CaHA) have been used for in the field of soft tissue augmentation. Both materials have been used in combination to enhance... (Review)
Review
Hyaluronic acid and calcium hydroxylapatite (CaHA) have been used for in the field of soft tissue augmentation. Both materials have been used in combination to enhance tissue remodeling and provide a more rejuvenated look. Sequential injections of Belotero Volume (CPM-HA V) and CaHA had a relatively greater remodeling effect on one's skin compared with the simultaneous injections of CPM-HA V and CaHA. Simultaneous injection of the studied products is possible from the point of view of safety, but different levels of administration will be more optimal, which will provide a more pronounced remodeling effect on the skin.
Topics: Humans; Durapatite; Dermal Fillers; Cosmetic Techniques; Hyaluronic Acid; Skin Aging; Esthetics
PubMed: 37977676
DOI: 10.1016/j.det.2023.06.011 -
Journal of Biomaterials Applications Sep 2023Atomic substitution or doping of a bioceramic material hydroxyapatite (HA) with specific ions is an appealing approach for improving its biocompatibility and activity,...
Atomic substitution or doping of a bioceramic material hydroxyapatite (HA) with specific ions is an appealing approach for improving its biocompatibility and activity, as well as imparting antibacterial properties. In this study, selenium- and/or copper-substituted hydroxyapatite powders were synthesized by an aqueous precipitation method and using the freeze-drying technique. The molar concentrations of constituents were calculated based on the proposed mechanism whereby selenium (Se) ions partially substitute phosphorus (P) sites, and copper (Cu) ions partially substitute (Ca) sites in the HA lattice. Dried precipitated samples were characterized using Inductively coupled plasma optical emission spectroscopy (ICP-OES), X-ray diffraction analysis (XRD), Fourier-transform infrared spectroscopy (FTIR) and Field-emission scanning electron microscopy with energy dispersive X-ray spectroscopy (FESEM-EDX). Accordingly, substitution of Se and/or Cu ions took place in the crystal lattice of HA without the formation of any impurities. The presence of sulphur (S) ions in the hydroxyapatite was detected by ICP-OES in all samples with copper substituted in the lattice. The cytotoxicity of the powders on osteoblastic (MC3T3-E1) cells was evaluated in vitro. Selenium substituted hydroxyapatite (SeHA), at the concentration (200 μg/mL), demonstrated higher populations of the live cells than that of control (cells without powders), suggesting that selenium may stimulate the proliferation of these cells. In addition, the copper substituted hydroxyapatite (CuHA) and the selenium and copper substituted hydroxyapatite (SeCuHA) at the concentrations (200 and 300 μg/mL) and (200 μg/mL), respectively demonstrated better results than the unsubstituted HA. Antimicrobial activity was assessed using a well-diffusion method against and , and superior results has obtained with SeCuHA . Presented findings imply that selenium and/or copper substituted modified hydroxyapatite nanoparticles, may be an attractive antimicrobial and cytocompatible substrate to be considered for use in a range of translational applications.
Topics: Selenium; Copper; Powders; Anti-Bacterial Agents; Durapatite
PubMed: 37604458
DOI: 10.1177/08853282231198726 -
Frontiers in Endocrinology 2023Dexamethasone (DEX) exerts anti-inflammatory and osteogenic effects. Hydroxyapatite is commonly used in bone repair due to its osteoconductivity, osseointegration, and...
BACKGROUND
Dexamethasone (DEX) exerts anti-inflammatory and osteogenic effects. Hydroxyapatite is commonly used in bone repair due to its osteoconductivity, osseointegration, and osteogenesis induction. Hollow hydroxyapatite (HHAM) is often used as a drug carrier.
OBJECTIVE
This study aimed to investigate the histological responses of exposed dental pulp when dexamethasone-loaded nanohydroxyapatite microspheres (DHHAM) were used as a direct capping agent.
METHODS
Cavities were created in the left maxillary first molar of Wistar rats and filled with Dycal, HHAM, and DHHAM. No drug was administered to the control group. The rats were sacrificed at 1, 2, and 4 weeks after the procedure. The molars were extracted for fixation, demineralization, dehydration, embedding, and sectioning. H&E staining was performed to detect the formation of reparative dentin. H&E and CD45 immunohistochemical staining were performed to detect pulp inflammation. Immunohistochemical staining was performed to assess the expressions of dentin matrix protein 1 (DMP-1), interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β.
RESULTS
The results of H&E and CD45 immunohistochemical staining showed that the degree of inflammation in the DHHAM group was less than that in the Control and HHAM groups at 1, 2, and 4 weeks after capping of the rat molar teeth (p<0.01). The H&E staining showed that the percentage of reparative dentin formed in the DHHAM group was higher than that in the Control, HHAM (p<0.001), and Dycal groups (p<0.01) at 1 and 2 weeks, and was significantly higher than that in the Control group (p<0.001) and the HHAM group (p<0.01) at 4 weeks. The immunohistochemical staining showed a lower range and intensity of expression of IL-1β, IL-6, and TNF-α and high expression levels of DMP-1 in the DHHAM group at 1, 2, and 4 weeks after pulp capping relative to the Control group.
CONCLUSIONS
DHHAM significantly inhibited the progression of inflammation and promoted reparative dentin formation.
Topics: Rats; Animals; Rats, Wistar; Dental Pulp Capping; Microspheres; Inflammation; Interleukin-6; Hydroxyapatites; Dexamethasone
PubMed: 37600685
DOI: 10.3389/fendo.2023.1192420 -
ACS Applied Bio Materials Dec 2023Ionic substitution can effectively activate the surface of hydroxyapatite (HA) for bone repair and regeneration processes. Therefore in this study, magnesium (Mg)-, zinc...
Ionic substitution can effectively activate the surface of hydroxyapatite (HA) for bone repair and regeneration processes. Therefore in this study, magnesium (Mg)-, zinc (Zn)-, and Mg/Zn-codoped HA was prepared by a hydrothermal method. The results of experimental and first-principles calculations verify the existence of Mg and Zn ions in the HA structure by altering cell parameters, crystallinity, and particle size. The results also showed that Mg and Zn are actively accommodated at the Ca(1) and Ca(2) positions, which not only inhibit HA formation but also promote calcium-deficient HA, and when the codoping content increased to 10%Mg and 10%Zn, the HA transformed completely to the whitlockite phase. Furthermore, the impact of codoping on biocompatibility was examined by employing MC3T3 cells. The in vitro study revealed that 5%Mg and 5%Zn single and -codoped HA promoted the proliferation of MC3T3 cells and 5%Mg-doped and -codoped HA stimulated MC3T3 cell differentiation, while 5%Zn-doped and -codoped HA revealed worthy antibacterial properties. Overall, the obtained results demonstrate that cosubstituted HA (5%Mg and 5%Zn) is promising, which not only eradicates bacteria ( and ) but also induces bone regeneration. These findings suggest that 5%Mg and 5%Zn binary-substituted HA is a very promising biomaterial for hard tissue scaffolds and bone repair.
Topics: Durapatite; Zinc; Magnesium; Biocompatible Materials; Anti-Bacterial Agents
PubMed: 37957165
DOI: 10.1021/acsabm.3c00599 -
Small (Weinheim An Der Bergstrasse,... Mar 2024Accumulation of reactive oxygen species (ROS) in periodontitis exacerbates the destruction of alveolar bone. Therefore, scavenging ROS to reshape the periodontal...
Accumulation of reactive oxygen species (ROS) in periodontitis exacerbates the destruction of alveolar bone. Therefore, scavenging ROS to reshape the periodontal microenvironment, alleviate the inflammatory response and promote endogenous stem cell osteogenic differentiation may be an effective strategy for treating bone resorption in periodontitis. In this study, sericin-hydroxyapatite nanoparticles (Se-nHA NPs) are synthesized using a biomimetic mineralization method. Se-nHA NPs and proanthocyanidins (PC) are then encapsulated in sericin/sodium alginate (Se/SA) using an electrostatic injection technique to prepare Se-nHA/PC microspheres. Microspheres are effective in scavenging ROS, inhibiting the polarization of macrophages toward the M1 type, and inducing the polarization of macrophages toward the M2 type. In normal or macrophage-conditioned media, the Se-nHA/PC microspheres effectively promoted the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). Furthermore, the Se-nHA/PC microspheres demonstrated anti-inflammatory effects in a periodontitis rat model by scavenging ROS and suppressing pro-inflammatory cytokines. The Se-nHA/PC microspheres are also distinguished by their capacity to decrease alveolar bone loss, reduce osteoclast activity, and boost osteogenic factor expression. Therefore, the biomimetic Se-nHA/PC composite microspheres have efficient ROS-scavenging, anti-inflammatory, and osteogenic abilities and can be used as a multifunctional filling material for inflammatory periodontal tissue regeneration.
Topics: Humans; Animals; Rats; Osteogenesis; Proanthocyanidins; Biomimetics; Microspheres; Reactive Oxygen Species; Sericins; Bone Regeneration; Periodontitis; Durapatite; Anti-Inflammatory Agents
PubMed: 37852940
DOI: 10.1002/smll.202305490