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Journal of Cellular Biochemistry Dec 2023We review unique properties of bone formation including current understanding of mechanisms of bone mineral transport. We focus on formation only; mechanism of bone... (Review)
Review
We review unique properties of bone formation including current understanding of mechanisms of bone mineral transport. We focus on formation only; mechanism of bone degradation is a separate topic not considered. Bone matrix is compared to other connective tissues composed mainly of the same proteins, but without the specialized mechanism for continuous transport and deposition of mineral. Indeed other connective tissues add mechanisms to prevent mineral formation. We start with the epithelial-like surfaces that mediate transport of phosphate to be incorporated into hydroxyapatite in bone, or in its ancestral tissue, the tooth. These include several phosphate producing or phosphate transport-related proteins with special expression in large quantities in bone, particularly in the bone-surface osteoblasts. In all connective tissues including bone, the proteins that constitute the protein matrix are mainly type I collagen and γ-carboxylate-containing small proteins in similar molar quantities to collagen. Specialized proteins that regulate connective tissue structure and formation are surprisingly similar in mineralized and non-mineralized tissues. While serum calcium and phosphate are adequate to precipitate mineral, specialized mechanisms normally prevent mineral formation except in bone, where continuous transport and deposition of mineral occurs.
Topics: Osteogenesis; Calcification, Physiologic; Bone and Bones; Collagen; Osteoblasts; Durapatite
PubMed: 37991446
DOI: 10.1002/jcb.30494 -
Bone Feb 2024Bone tissue engineering holds great promise for the regeneration of damaged or severe bone defects. However, several challenges hinder its translation into clinical... (Review)
Review
Bone tissue engineering holds great promise for the regeneration of damaged or severe bone defects. However, several challenges hinder its translation into clinical practice. To address these challenges, interdisciplinary efforts and advances in biomaterials, cell biology, and bioengineering are required. In recent years, nano-hydroxyapatite (nHA)-based scaffolds have emerged as a promising approach for the development of bone regenerative agents. The unique similarity of nHA with minerals found in natural bones promotes remineralization and stimulates bone growth, which are crucial factors for efficient bone regeneration. Moreover, nHA exhibits desirable properties, such as strong chemical interactions with bone and facilitation of tissue growth, without inducing inflammation or toxicity. It also promotes osteoblast survival, adhesion, and proliferation, as well as increasing alkaline phosphatase activity, osteogenic differentiation, and bone-specific gene expression. However, it is important to note that the effect of nHA on osteoblast behavior is dose-dependent, with cytotoxic effects observed at higher doses. Additionally, the particle size of nHA plays a crucial role, with smaller particles having a more significant impact. Therefore, in this review, we highlighted the potential of nHA for improving bone regeneration processes and summarized the available data on bone cell response to nHA-based scaffolds. In addition, an attempt is made to portray the current status of bone tissue engineering using nHA/polymer hybrids and some recent scientific research in the field.
Topics: Durapatite; Osteogenesis; Tissue Scaffolds; Regenerative Medicine; Biocompatible Materials; Tissue Engineering; Bone Regeneration
PubMed: 37951520
DOI: 10.1016/j.bone.2023.116956 -
Environmental Research Oct 2023Multi-metals/metalloids contaminated soil has received extensive attention because of their adverse health effects on the safety of the food chain and environmental...
Simultaneous immobilization of lead and arsenic and improved phosphorus availability in contaminated soil using biochar composite modified with hydroxyapatite and oxidation: Findings from a pot experiment.
Multi-metals/metalloids contaminated soil has received extensive attention because of their adverse health effects on the safety of the food chain and environmental health. In order to provide additional insight and aid in mitigating environmental risks, a pot experiment was directed to assess the impacts of biochars derived from rice straw (BC), and modified biochars i-e., hydroxyapatite modified (HAP-BC) and oxidized biochars (Ox-BC) on the redistribution, phytoavailability and bioavailability of phosphorus (P), lead (Pb), and Arsenic (As), as well as their effects on the growth of maize (Zea mays L.) in a Lead (Pb)/Arsenic (As) contaminated soil. The results showed that HAP-BC increased the soil total and available P, compared with raw biochar and control treatment. HAP-BC improved soil properties by elevating soil pH and electric conductivity (EC). The Hedley fractionation scheme revealed that HAP-BC enhanced the labile and moderately labile P species in soil. Both HAP-BC and Ox-BC assisted in the P build-up in plant roots and shoots. The BCR (European Community Bureau of Reference) sequential extraction data for Pb and As in soil showed the pronounced effects of HAP-BC towards the transformation of labile Pb and As forms into more stable species. Compared with control, HAP-BC significantly (P ≤ 0.05) decreased the DTPA-extractable Pb and As by 55% and 28%, respectively, subsequently, resulting in reduced Pb and As plant uptakes. HAP-BC application increased the plant fresh and dry root/shoot biomass by 239%, 72%, 222% and 190%, respectively. The Pb/As immobilization by HAP-BC was mainly driven by precipitation, ion exchange and surface complexation mechanisms in soil. In general, HAP-BC application indicated a great capability to be employed as an effective alternative soil amendment for improving P acquisition in soil, simultaneously immobilizing Pb and As in the soil-plant systems.
Topics: Arsenic; Lead; Phosphorus; Durapatite; Soil Pollutants; Cadmium; Soil; Zea mays
PubMed: 37453505
DOI: 10.1016/j.envres.2023.116640 -
International Journal of Nanomedicine 2023This study aims to investigate the impact of enhancing subchondral bone repair on the efficacy of articular cartilage restoration, thereby achieving improved...
PURPOSE
This study aims to investigate the impact of enhancing subchondral bone repair on the efficacy of articular cartilage restoration, thereby achieving improved osteochondral regeneration outcomes.
METHODS
In this study, we modified the surface of nano-hydroxyapatite (n-HAp) through alkylation reactions to prepare n-HApMA. Characterization techniques, including X-ray diffraction, infrared spectroscopy scanning, thermogravimetric analysis, particle size analysis, and electron microscopy, were employed to analyze n-HApMA. Bioinks were prepared using n-HApMA, high porosity GelMA hydrogel, and adipose tissue derived stromal cells (ADSCs). The rheological properties of the bioinks during photocuring were investigated using a rheometer. Based on these bioinks, a biphasic scaffold was constructed. The viability of cells within the scaffold was observed using live-dead cell staining, while the internal morphology was examined using scanning electron microscopy. The stiffness of the scaffold was evaluated through compression testing. Scaffolds were implanted into the osteochondral defects of New Zealand rabbit knees, and microCT was utilized to observe the subchondral bone repair. Hematoxylin and eosin (H&E) staining, Masson's trichrome staining, and Safranin O/Fast Green staining were performed to assess the regeneration of subchondral bone and cartilage. Furthermore, immunohistochemical staining was employed to detect the expression of osteogenic and chondrogenic-related molecules.
RESULTS
Scaffold characterization revealed that surface modification enables the uniform distribution of n-HApMA within the GelMA matrix. The incorporation of 5% n-HApMA notably enhanced the elastic modulus and stiffness of the 6% high-porosity GelMA in comparison to n-HAp. Moreover, in-vivo study showed that the homogeneous dispersion of n-HApMA on the GelMA matrix facilitated the osteogenic differentiation of adipose-derived stem cells (ADSCs) and promoted osteochondral tissue regeneration.
CONCLUSION
These findings suggest potential applications of the n-HApMA/GelMA composite in the field of tissue engineering and regenerative medicine.
Topics: Animals; Rabbits; Tissue Scaffolds; Osteogenesis; Durapatite; Porosity; Mesenchymal Stem Cells; Tissue Engineering; Cartilage, Articular; Biocompatible Materials
PubMed: 37886722
DOI: 10.2147/IJN.S428965 -
Cancer Biology & Medicine Feb 2024Immune adjuvants are immune modulators that have been developed in the context of infectious vaccinations. There is currently a growing interest in immune adjuvants due... (Review)
Review
Immune adjuvants are immune modulators that have been developed in the context of infectious vaccinations. There is currently a growing interest in immune adjuvants due to the development of immunotherapy against cancers. Immune adjuvant mechanisms of action are focused on the initiation and amplification of the inflammatory response leading to the innate immune response, followed by the adaptive immune response. The main activity lies in the support of antigen presentation and the maturation and functions of dendritic cells. Most immune adjuvants are associated with a vaccine or incorporated into the new generation of mRNA vaccines. Few immune adjuvants are used as drugs. Hydroxyapatite (HA) ceramics and azoximer bromide (AZB) are overlooked molecules that were used in early clinical trials, which demonstrated clinical efficacy and excellent tolerance profiles. HA combined in an autologous vaccine was previously developed in the veterinary field for use in canine spontaneous lymphomas. AZB, an original immune modulator derived from a class of heterochain aliphatic polyamines that is licensed in Russia, the Commonwealth of Independent States, and Slovakia for infectious and inflammatory diseases, is and now being developed for use in cancer with promising results. These two immune adjuvants can be combined in various immunotherapy strategies.
Topics: Animals; Dogs; Humans; Adjuvants, Immunologic; Vaccines; Neoplasms; Hydroxyapatites; Piperazines; Polymers
PubMed: 38318840
DOI: 10.20892/j.issn.2095-3941.2023.0222 -
Cancer Medicine Feb 2024It has been shown that tumor microenvironment (TME) hydroxyapatite (HAP) is typically associated with many malignancies and plays a role in tumor progression and growth....
BACKGROUND
It has been shown that tumor microenvironment (TME) hydroxyapatite (HAP) is typically associated with many malignancies and plays a role in tumor progression and growth. Additionally, acidosis in the TME has been reported to play a key role in selecting for a more aggressive tumor phenotype, drug resistance and desensitization to immunotherapy for many types of cancers. TME-HAP is an attractive target for tumor detection and treatment development since HAP is generally absent from normal soft tissue. We provide strong evidence that dissolution of hydroxyapatite (HAP) within the tumor microenvironment (TME-HAP) using a novel therapeutic can be used to kill cancer cells both in vitro and in vivo with minimal adverse effects.
METHODS
We developed an injectable cation exchange nano particulate sulfonated polystyrene solution (NSPS) that we engineered to dissolve TME-HAP, inducing localized acute alkalosis and inhibition of tumor growth and glucose metabolism. This was evaluated in cell culture using 4T1, MDA-MB-231 triple negative breast cancer cells, MCF10 normal breast cells, and H292 lung cancer cells, and in vivo using orthotopic mouse models of cancer that contained detectable microenvironment HAP including breast (MMTV-Neu, 4T1, and MDA-MB-231), prostate (PC3) and colon (HCA7) cancer using F-NaF for HAP and F-FDG for glucose metabolism with PET imaging. On the other hand, H292 lung tumor cells that lacked detectable microenvironment HAP and MCF10a normal breast cells that do not produce HAP served as negative controls. Tumor microenvironment pH levels following injection of NSPS were evaluated via Chemical Exchange Saturation (CEST) MRI and via ex vivo methods.
RESULTS
Within 24 h of adding the small concentration of 1X of NSPS (~7 μM), we observed significant tumor cell death (~ 10%, p < 0.05) in 4T1 and MDA-MB-231 cell cultures that contain HAP but ⟨2% in H292 and MCF10a cells that lack detectable HAP and in controls. Using CEST MRI, we found extracellular pH (pHe) in the 4T1 breast tumors, located in the mammary fat pad, to increase by nearly 10% from baseline before gradually receding back to baseline during the first hour post NSPS administration. in the tumors that contained TME-HAP in mouse models, MMTV-Neu, 4T1, and MDA-MB-231, PC3, and HCA7, there was a significant reduction (p<0.05) in F-Na Fuptake post NSPS treatment as expected; F uptake in the tumor = 3.8 ± 0.5 %ID/g (percent of the injected dose per gram) at baseline compared to 1.8 ±0.5 %ID/g following one-time treatment with 100 mg/kg NSPS. Of similar importance, is that F-FDG uptake in the tumors was reduced by more than 75% compared to baseline within 24 h of treatment with one-time NSPS which persisted for at least one week. Additionally, tumor growth was significantly slower (p < 0.05) in the mice treated with one-time NSPS. Toxicity showed no evidence of any adverse effects, a finding attributed to the absence of HAP in normal soft tissue and to our therapeutic NSPS having limited penetration to access HAP within skeletal bone.
CONCLUSION
Dissolution of TME-HAP using our novel NSPS has the potential to provide a new treatment paradigm to enhance the management of cancer patients with poor prognosis.
Topics: Humans; Male; Animals; Mice; Pharmaceutical Preparations; Fluorodeoxyglucose F18; Immunotherapy; Drug-Related Side Effects and Adverse Reactions; Lung Neoplasms; Alkanesulfonates; Glucose; Hydroxyapatites; Tumor Microenvironment
PubMed: 38239047
DOI: 10.1002/cam4.6812 -
International Journal of Biological... Jul 2023Hydroxyapatite (HA) and chitosan (CS) biopolymer are the major materials investigated for biomedical purposes. Both of these components play an important role in the... (Review)
Review
Hydroxyapatite (HA) and chitosan (CS) biopolymer are the major materials investigated for biomedical purposes. Both of these components play an important role in the orthopedic field as bone substitutes or drug release systems. Used separately, the hydroxyapatite is quite fragile, while CS mechanical strength is very weak. Therefore, a combination of HA and CS polymer is used, which provides excellent mechanical performance with high biocompatibility and biomimetic capacity. Moreover, the porous structure and reactivity of the hydroxyapatite-chitosan (HA-CS) composite allow their application not only as a bone repair but also as a drug delivery system providing controlled drug release directly to the bone site. These features make biomimetic HA-CS composite a subject of interest for many researchers. Through this review, we provide the important recent achievements in the development of HA-CS composites, focusing on manufacturing techniques, conventional and novel three-dimensional bioprinting technology, and physicochemical and biological properties. The drug delivery properties and the most relevant biomedical applications of the HA-CS composite scaffolds are also presented. Finally, alternative approaches are proposed to develop HA composites with the aim to improve their physicochemical, mechanical, and biological properties.
Topics: Chitosan; Durapatite; Biocompatible Materials; Tissue Engineering; Bone Regeneration; Tissue Scaffolds
PubMed: 37285882
DOI: 10.1016/j.ijbiomac.2023.125150 -
Chemosphere Mar 2024Hydroxyapatite (HA) is a biomaterial widely used in clinical applications and pharmaceuticals. The literature on HA-based materials studies is focused on chemical... (Review)
Review
Hydroxyapatite (HA) is a biomaterial widely used in clinical applications and pharmaceuticals. The literature on HA-based materials studies is focused on chemical characterization and biocompatibility. Generally, biocompatibility is analyzed through adhesion, proliferation, and differentiation assays. Fewer studies are looking for genotoxic events. Thus, although HA-based biomaterials are widely used as biomedical devices, there is a lack of literature regarding their genotoxicity. This systematic review was carried out following the PRISMA statement. Specific search strategies were developed and performed in four electronic databases (PubMed, Science Direct, Scopus, and Web of Science). The search used "Hydroxyapatite OR Calcium Hydroxyapatite OR durapatite AND genotoxicity OR genotoxic OR DNA damage" and "Hydroxyapatite OR Calcium Hydroxyapatite OR durapatite AND mutagenicity OR mutagenic OR DNA damage" as keywords and articles published from 2000 to 2022, after removing duplicate studies and apply include and exclusion criteria, 53 articles were identified and submitted to a qualitative descriptive analysis. Most of the assays were in vitro and most of the studies did not show genotoxicity. In fact, a protective effect was observed for hydroxyapatites. Only 20 out of 71 tests performed were positive for genotoxicity. However, no point mutation-related mutagenicity was observed. As the genotoxicity of HA-based biomaterials observed was correlated with its nanostructured forms as needles or rods, it is important to follow their effect in chronic exposure to guarantee safe usage in humans.
Topics: Humans; Durapatite; Biocompatible Materials; Hydroxyapatites; DNA Damage; Mutagens
PubMed: 38360416
DOI: 10.1016/j.chemosphere.2024.141383 -
Biomaterials Advances Apr 2024The grand discovery of morphogens, or "form-generating substances", revealed that tissue morphogenesis is initiated by soluble molecular signals or morphogens primarily... (Review)
Review
The grand discovery of morphogens, or "form-generating substances", revealed that tissue morphogenesis is initiated by soluble molecular signals or morphogens primarily belonging to the transforming growth factor-β (TGF-β) supergene family. The regenerative potential of bone rests on its extracellular matrix, which is the repository of several morphogens that tightly control cellular differentiating pathways, cellular matrix deposition and remodeling. Alluringly, the matrix also contains specific factors transferred from the heterotopic implanted bone matrices initiating "Tissue Induction", as provocatively described in Nature in 1945. Later, it was found that selected genes and gene products of the TGF-β supergene family singly, synchronously, and synergistically mastermind the induction of bone formation. This review describes the phenomenon of the spontaneous and/or intrinsic osteoinductivity of calcium phosphate-based biomaterials and titanium' constructs without the applications of soluble osteogenetic molecular signals. The review shows the spontaneous induction of bone formation initiated by Ca++ activating stem cell differentiation and up-regulation of bone morphogenetic proteins genes. Expressed gene products are embedded into the concavities of the calcium phosphate-based substrata, initiating bone formation as a secondary response. Pure titanium's substrata do not initiate the spontaneous induction of bone formation. The induction of bone is solely dependent on acid, alkali and heat treatments to form apatite layers on the treated titanium surfaces. The induction of bone formation is achieved exclusively by apatite-based biomaterial surfaces. The hydroxyapatite, in its various forms and geometric configurations, finely tunes the induction of bone formation in heterotopic sites. Cellular differentiation by fine-tuning of the cellular molecular machinery is initiated by specific geometric modularity of the hydroxyapatite substrata that push cellular buttons that start the ripple-like cascade of "Tissue Induction", generating newly formed ossicles with bone marrow in heterotopic extraskeletal sites. The highlighted mechanistic insights into the spontaneous induction of bone formation are a research platform invocating selected molecular elements to construct the induction of bone formation.
Topics: Osteogenesis; Titanium; Apatites; Biocompatible Materials; Durapatite; Transforming Growth Factor beta; Calcium Phosphates
PubMed: 38335762
DOI: 10.1016/j.bioadv.2024.213795 -
Scientific Reports Oct 2023Biomaterial engineering approaches involve using a combination of miscellaneous bioactive molecules which may promote cell proliferation and, thus, form a scaffold with...
Biomaterial engineering approaches involve using a combination of miscellaneous bioactive molecules which may promote cell proliferation and, thus, form a scaffold with the environment that favors the regeneration process. Chitosan, a naturally occurring biodegradable polymer, possess some essential features, i.e., biodegradability, biocompatibility, and in the solid phase good porosity, which may contribute to promote cell adhesion. Moreover, doping of the materials with other biocompounds will create a unique and multifunctional scaffold that will be useful in regenerative medicine. This study is focused on the manufacturing and characterization of composite materials based on chitosan, hydroxyapatite, and riboflavin. The resulting films were fabricated by the casting/solvent evaporation method. Morphological and spectroscopy analyses of the films revealed a porous structure and an interconnection between chitosan and apatite. The composite material showed an inhibitory effect on Staphylococcus aureus and exhibited higher antioxidant activity compared to pure chitosan. In vitro studies on riboflavin showed increased cell proliferation and migration of fibroblasts and osteosarcoma cells, thus demonstrating their potential for bone tissue engineering applications.
Topics: Biocompatible Materials; Chitosan; Durapatite; Tissue Scaffolds; Tissue Engineering; Bone Regeneration; Porosity; Riboflavin
PubMed: 37813934
DOI: 10.1038/s41598-023-44225-0