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Proceedings of the National Academy of... Apr 2023DNA-based biomaterials have been proposed for tissue engineering approaches due to their predictable assembly into complex morphologies and ease of functionalization....
DNA-based biomaterials have been proposed for tissue engineering approaches due to their predictable assembly into complex morphologies and ease of functionalization. For bone tissue regeneration, the ability to bind Ca and promote hydroxyapatite (HAP) growth along the DNA backbone combined with their degradation and release of extracellular phosphate, a known promoter of osteogenic differentiation, make DNA-based biomaterials unlike other currently used materials. However, their use as biodegradable scaffolds for bone repair remains scarce. Here, we describe the design and synthesis of DNA hydrogels, gels composed of DNA that swell in water, their interactions in vitro with the osteogenic cell lines MC3T3-E1 and mouse calvarial osteoblast, and their promotion of new bone formation in rat calvarial wounds. We found that DNA hydrogels can be readily synthesized at room temperature, and they promote HAP growth in vitro, as characterized by Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, atomic force microscopy, and transmission electron microscopy. Osteogenic cells remain viable when seeded on DNA hydrogels in vitro, as characterized by fluorescence microscopy. In vivo, DNA hydrogels promote the formation of new bone in rat calvarial critical size defects, as characterized by micro-computed tomography and histology. This study uses DNA hydrogels as a potential therapeutic biomaterial for regenerating lost bone.
Topics: Mice; Rats; Animals; Osteogenesis; Hydrogels; X-Ray Microtomography; Bone Regeneration; Biocompatible Materials; Durapatite; Tissue Engineering; Tissue Scaffolds
PubMed: 37071684
DOI: 10.1073/pnas.2220565120 -
Hand Clinics Feb 2024We examine the range of available bone graft substitutes often used in nonunion and malunion surgery of the upper extremity. Synthetic materials such as calcium sulfate,... (Review)
Review
We examine the range of available bone graft substitutes often used in nonunion and malunion surgery of the upper extremity. Synthetic materials such as calcium sulfate, beta-calcium phosphate ceramics, hydroxyapatite, bioactive glass, and 3D printed materials are discussed. We delve into the advantages, disadvantages, and clinical applications for each, considering factors such as biocompatibility, osteoconductivity, mechanical strength, and resorption rates. This review provides upper extremity surgeons with insights into the available array of bone graft substitutes. We hope that the reviews helps in the decision-making process to achieve optimal outcomes when treating nonunion and malunion of the upper extremity.
Topics: Humans; Bone Substitutes; Durapatite; Bone Transplantation; Glass
PubMed: 37979985
DOI: 10.1016/j.hcl.2023.09.001 -
The International Journal of... 2023For the past 50 years, hydroxyapatite (HA) has been widely used in bone defect repair because it is the main inorganic component of the mineral phase of a human bone.... (Review)
Review
For the past 50 years, hydroxyapatite (HA) has been widely used in bone defect repair because it is the main inorganic component of the mineral phase of a human bone. Extensive preclinical and clinical studies have shown that strontium (Sr) can safely and effectively help prevent and treat bone diseases, including osteoporosis. These findings have resulted in the concept of integrating Sr and HA for bone disease management. The doped Sr can improve the physicochemical properties of HA and enhance its angiogenic and bone regeneration ability. Nevertheless, no study has reviewed the design strategy of Sr-doped HA (Sr-HA) to understand its biological roles. Therefore, in this article, we review recent developments in Sr-HA preparation and its effect on osteogenesis and angiogenesis and along with key suggestions for future research and development.
Topics: Humans; Osteogenesis; Angiogenesis; Hydroxyapatites; Durapatite; Strontium
PubMed: 37975329
DOI: 10.1387/ijdb.230091lc -
ACS Biomaterials Science & Engineering Aug 2022Being a bioactive material, hydroxyapatite (HAp) is regarded as one of the most attractive ceramic biomaterials for bone and hard-tissue replacement and regeneration.... (Review)
Review
Being a bioactive material, hydroxyapatite (HAp) is regarded as one of the most attractive ceramic biomaterials for bone and hard-tissue replacement and regeneration. Despite its substantial biocompatibility, osteoconductivity, and compositional similarity to that of bone, the employment of HAp is still limited in orthopedic applications due to its poor mechanical (low fracture toughness and bending strength) and antibacterial properties. These significant challenges lead to the notion of developing novel HAp-based composites via different fabrication routes. HAp, when efficaciously combined with functionally graded materials and antibacterial agents, like Ag, ZnO, Co, etc., form composites that render remarkable crack resistance and toughening, as well as enhance its bactericidal efficacy. The addition of different materials and a fabrication method, like 3D printing, greatly influence the porosity of the structure and, in turn, control cell adhesion, thereby enabling biological fixation of the material. This article encompasses an elaborate discussion on different multifunctional HAp composites developed for orthopedic applications with particular emphasis on the incorporation of functionally graded materials and antibacterial agents. The influence of 3D printing on the fabrication of HAp-based scaffolds, and the different in vitro and in vivo studies conducted on these, have all been included here. Furthermore, the present review not only provides insights and broad understanding by elucidating recent advancements toward 4D printing but also directs the reader to future research directions in design and application of HAp-based composite coatings and scaffolds.
Topics: Anti-Bacterial Agents; Biocompatible Materials; Bone Regeneration; Bone Substitutes; Durapatite
PubMed: 35838237
DOI: 10.1021/acsbiomaterials.2c00140 -
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 -
International Journal of Nanomedicine 2022Hydroxyapatite (HA) is similar to natural bone regarding composition, and its structure favors in biomedical applications. Continuous research and progress on HA... (Review)
Review
Hydroxyapatite (HA) is similar to natural bone regarding composition, and its structure favors in biomedical applications. Continuous research and progress on HA nanomaterials (HA-NMs) have explored novel fabrication approaches coupled with functionalization and characterization methods. These nanomaterials have a significant role in many biomedical areas like sustained drug and gene delivery, bio-imaging, magnetic resonance, cell separation, and hyperthermia treatment due to their promising biocompatibility. This review highlighted the HA-NMs chemical composition, recent progress in synthesis methods, characterization and surface modification methods, ion-doping, and role in biomedical applications. HA-NMs have a substantial role as drug delivery vehicles, coating material, bone implant, coating, ceramic, and composite materials. Here, we try to summarize an overview of HA-NMs with the provision of future directions.
Topics: Bone and Bones; Ceramics; Drug Delivery Systems; Durapatite; Nanostructures
PubMed: 35530974
DOI: 10.2147/IJN.S360670 -
International Journal of Molecular... Sep 2022Great advances in cancer treatment have been undertaken in the last years as a consequence of the development of new antitumoral drugs able to target cancer cells with... (Review)
Review
Great advances in cancer treatment have been undertaken in the last years as a consequence of the development of new antitumoral drugs able to target cancer cells with decreasing side effects and a better understanding of the behavior of neoplastic cells during invasion and metastasis. Specifically, drug delivery systems (DDS) based on the use of hydroxyapatite nanoparticles (HAp NPs) are gaining attention and merit a comprehensive review focused on their potential applications. These are derived from the intrinsic properties of HAp (e.g., biocompatibility and biodegradability), together with the easy functionalization and easy control of porosity, crystallinity and morphology of HAp NPs. The capacity to tailor the properties of DLS based on HAp NPs has well-recognized advantages for the control of both drug loading and release. Furthermore, the functionalization of NPs allows a targeted uptake in tumoral cells while their rapid elimination by the reticuloendothelial system (RES) can be avoided. Advances in HAp NPs involve not only their use as drug nanocarriers but also their employment as nanosystems for magnetic hyperthermia therapy, gene delivery systems, adjuvants for cancer immunotherapy and nanoparticles for cell imaging.
Topics: Drug Delivery Systems; Durapatite; Humans; Nanoparticles; Neoplasms; Porosity
PubMed: 36232652
DOI: 10.3390/ijms231911352 -
Immunomodulatory Properties: The Accelerant of Hydroxyapatite-Based Materials for Bone Regeneration.Tissue Engineering. Part C, Methods Aug 2022The immunoinflammatory response is the prerequisite step for wound healing and tissue regeneration, and the immunomodulatory effects of biomaterials have attracted... (Review)
Review
The immunoinflammatory response is the prerequisite step for wound healing and tissue regeneration, and the immunomodulatory effects of biomaterials have attracted increasing attention. Hydroxyapatite [Ca(PO)(OH)] (HAp), a common calcium phosphate ceramic, due to its structural and functional similarity to the inorganic constituent of natural bones, has been developed for different application purposes such as bone substitutes, tissue engineering scaffolds, and implant coatings. Recently, the interaction between HAp-based materials and the immune system (various immune cells), and the immunomodulatory effects of HAp-based materials on bone tissue regeneration have been explored extensively. Macrophages-mediated regenerative effect by HAp stimulation occupies the mainstream status of immunomodulatory strategies. The immunomodulation of HAp can be manipulated by tuning the physical, chemical, and biological cues such as surface functionalization (physical or chemical modifications), structural and textural characteristics (size, shape, and surface topography), and the incorporation of bioactive substances (cytokines, rare-earth elements, and bioactive ions). Therefore, HAp ceramic materials can contribute to bone regeneration by creating a favorable osteoimmune microenvironment, which would provide a more comprehensive theoretical basis for their further clinical applications. Considering the rapidly developed HAp-based materials as well as their excellent biological performances in the field of regenerative medicine, this review discusses the recent advances concerning the immunomodulatory methods for HAp-based biomaterials and their roles in bone tissue regeneration. Impact statement This review summarized the immunomodulatory methods for hydroxyapatite-based biomaterials in bone tissue regeneration, and further discussed the affecting factors of immunomodulation as well as the challenges for the immunomodulatory strategies. The comprehensive understanding of immunomodulatory strategies for tissue regeneration would provide more guidance for the development of novel hydroxyapatite composite biomaterials.
Topics: Biocompatible Materials; Bone Regeneration; Durapatite; Immunomodulation; Osteogenesis; Tissue Engineering; Tissue Scaffolds
PubMed: 35196904
DOI: 10.1089/ten.TEC.2022.00111112 -
Artificial Cells, Nanomedicine, and... Dec 2021Nano-hydroxyapatite is being investigated as vital components of implants and dental and tissue engineering devices. It is found as a bone replacement due to its... (Review)
Review
Nano-hydroxyapatite is being investigated as vital components of implants and dental and tissue engineering devices. It is found as a bone replacement due to its non-toxicity and cytocompatibility with dental tissues and bone. The reality that nanocrystalline hydroxyapatite can be made of porous granules and scaffolds. Additionally, it has a massive loading potential indicating its use as a transporter for drugs or a regulated drug release mechanism in pharmaceutical research. This review aims to present existing nano-hydroxyapatite research developments as a drug carrier employed in bone tissue disorders locally and deliver poorly soluble drugs with reduced bioavailability. We have discussed the nano-hydroxyapatite role in the delivery of drugs (i.e. anti-resorptive, anti-cancer, and antibiotics), proteins, genetic material, and radionuclides.
Topics: Drug Carriers; Durapatite; Porosity; Tissue Engineering; Tissue Scaffolds
PubMed: 34907839
DOI: 10.1080/21691401.2021.2016785 -
Tissue Engineering. Part A Jan 2022Tissue engineering and regenerative medicine has gradually evolved as a promising therapeutic strategy to the modern health care of aging and diseased population. In...
Tissue engineering and regenerative medicine has gradually evolved as a promising therapeutic strategy to the modern health care of aging and diseased population. In this study, we developed a novel nanofibrous scaffold and verified its application in the critical bone defect regeneration. The metformin-incorporated nano-gelatin/hydroxyapatite fibers (NGF) was produced by electrospinning, cross-linked, and then characterized by X-ray powder diffractometer and Fourier-transform infrared spectroscopy. Cytotoxicity, cell adhesion, cell differentiation, and quantitative osteogenic gene and protein expression were analyzed by bone marrow stem cells (BMSCs) from rat. Rat forearm critical bone defect model was performed for the study. The NGF were characterized by their porous structures with proper interconnectivity without significant cytotoxic effects; the adhesion of BMSCs on the NGF could be enhanced. The osteogenic gene and protein expression were upregulated. Postimplantation, the new regenerated bone in bone defect was well demonstrated in the NGF samples. We demonstrated that the metformin-incorporated NGF greatly improved healing potential on the critical-size bone defect. Although metformin-incorporated NGF had advantageous effectiveness during bone regeneration, further validation is required before it can be applied to clinical applications. Impact statement Bone is the structure that supports the rest of the human body. Critical-size bone defect hinders the regeneration of damaged bone tissues and compromises the mechanical strength of the skeletal system. Characterized by their porous structures with proper interconnectivity, the electrospinning nano-gelatin/hydroxyapatite fibrous scaffold developed in this study can greatly improve the healing potential on the critical-size bone defect. Further validation can validate its potential clinical applications.
Topics: Animals; Bone Regeneration; Durapatite; Gelatin; Metformin; Nanofibers; Osteogenesis; Rats; Tissue Engineering; Tissue Scaffolds
PubMed: 33971745
DOI: 10.1089/ten.TEA.2021.0038