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Theranostics 2020Globally, more than 1.5 million patients undergo bone graft surgeries annually, and the development of biomaterial scaffolds that mimic natural bone for bone grafting... (Review)
Review
Globally, more than 1.5 million patients undergo bone graft surgeries annually, and the development of biomaterial scaffolds that mimic natural bone for bone grafting remains a tremendous challenge. In recent decades, due to the improved understanding of the mechanisms of bone remodeling and the rapid development of gene therapy, RNA (including messenger RNA (mRNA), microRNA (miRNA), and short interfering RNA (siRNA)) has attracted increased attention as a new tool for bone tissue engineering due to its unique nature and great potential to cure bone defects. Different types of RNA play roles a variety of mechanisms in bone-related cells as well as after synthesis . In addition, RNAs are delivered to injured sites by loading into scaffolds or systemic administration after combination with vectors for bone tissue engineering. However, the challenge of effectively and stably delivering RNA into local tissue remains to be solved. This review describes the mechanisms of the three types of RNAs and the application of the relevant types of RNA delivery vectors and scaffolds in bone regeneration. The improvements in their development are also discussed.
Topics: Animals; Bone Regeneration; Collagen; Drug Delivery Systems; Durapatite; Humans; Hydrogels; MicroRNAs; Osteoclasts; RNA Processing, Post-Transcriptional; RNA Stability; RNA, Messenger; RNA, Small Interfering; Rats; Tissue Scaffolds; Transcription, Genetic
PubMed: 32194862
DOI: 10.7150/thno.42640 -
Pharmaceutical Research Jun 2017Bone morphogenetic proteins (BMPs) are responsible for bone formation during embryogenesis and bone regeneration and remodeling. The osteoinductive action of BMPs,... (Review)
Review
Bone morphogenetic proteins (BMPs) are responsible for bone formation during embryogenesis and bone regeneration and remodeling. The osteoinductive action of BMPs, especially BMP-2 and BMP-7, has led to their use in a range of insurmountable treatments where intervention is required for effective bone regeneration. Introduction of BMP products to the market, however, was not without reports of multiple complications and side effects. Aiming for optimization of the therapeutic efficacy and safety, efforts have been focused on improving the delivery of BMPs to lower the administered dose, localize the protein, and prolong its retention time at the site of action. A major challenge with these efforts is that the protein stability should be maintained. With this review we attempt to shed light on how the stability of BMPs can be affected in the formulation and delivery processes. We first provide a short overview of the current standing of the complications experienced with BMP products. We then discuss the different delivery parameters studied in association with BMPs, and their influence on the efficacy and safety of BMP treatments. In particular, the literature addressing the stability of BMPs and their possible interactions with components of the delivery system as well as their sensitivity to conditions of the formulation process is reviewed. In summary, recent developments in the fields of bioengineering and biopharmaceuticals suggest that a good understanding of the relationship between the formulation/delivery conditions and the stability of growth factors such as BMPs is a prerequisite for a safe and effective treatment.
Topics: Animals; Bone Morphogenetic Proteins; Bone Regeneration; Drug Compounding; Drug Delivery Systems; Drug Liberation; Drug Stability; Humans; Polymers; Signal Transduction; Tissue Engineering; Tissue Scaffolds
PubMed: 28342056
DOI: 10.1007/s11095-017-2147-x -
Journal of Dental Research Feb 2014The bone-regenerative potentials of the periosteum have been explored as early as the 17th century. Over the past few years, however, much has been discovered in terms... (Review)
Review
The bone-regenerative potentials of the periosteum have been explored as early as the 17th century. Over the past few years, however, much has been discovered in terms of the molecular and cellular mechanisms that control the periosteal contribution to bone regeneration. Lineage tracing analyses and knock-in transgenic mice have helped define the relative contributions of the periosteum and endosteum to bone regeneration. Additional studies have shed light on the critical roles that BMP, FGF, Hedgehog, Notch, PDGF, Wnt, and inflammation signaling have or may have in periosteal-mediated bone regeneration, fostering the path to novel approaches in bone-regenerative therapy. Thus, by examining the role that each pathway has in periosteal-mediated bone regeneration, in this review we analyze the status of the current research on the regenerative potential of the periosteum. The provided analysis aims to inform both clinician-scientists who may have interest in the current studies about the biology of the periosteum as well as dental surgeons who may find this review useful to perform periosteal-harnessing bone-regenerative procedures.
Topics: Animals; Biology; Bone Regeneration; Cell Lineage; Facial Bones; Humans; Intercellular Signaling Peptides and Proteins; Periosteum; Signal Transduction; Skull; Tissue Engineering
PubMed: 24088412
DOI: 10.1177/0022034513506445 -
Stem Cell Research & Therapy Jul 2021Over the past decades, many studies focused on mesenchymal stem cells (MSCs) therapy for bone regeneration. Due to the efficiency of topical application has been widely... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Over the past decades, many studies focused on mesenchymal stem cells (MSCs) therapy for bone regeneration. Due to the efficiency of topical application has been widely dicussed and systemic application was also a feasible way for new bone formation, the aim of this study was to systematically review systemic therapy of MSCs for bone regeneration in pre-clinical studies.
METHODS
The article search was conducted in PubMed and Embase databases. Original research articles that assessed potential effect of systemic application of MSCs for bone regeneration in vivo were selected and evaluated in this review, according to eligibility criteria. The efficacy of MSC systemic treatment was analyzed by random effects meta-analysis, and the outcomes were expressed in standard mean difference (SMD) and its 95% confidence interval. Subgroup analyses were conducted on animal species and gender, MSCs types, frequency and time of injection, and bone diseases.
RESULTS
Twenty-three articles were selected in this review, of which 21 were included in meta-analysis. The results showed that systemic therapy increased bone mineral density (SMD 3.02 [1.84, 4.20]), bone volume to tissue volume ratio (2.10 [1.16, 3.03]), and the percentage of new bone area (7.03 [2.10, 11.96]). Bone loss caused by systemic disease tended to produce a better response to systemic treatment (p=0.05 in BMD, p=0.03 in BV/TV).
CONCLUSION
This study concluded that systemic therapy of MSCs promotes bone regeneration in preclinical experiments. These results provided important information for the systemic application of MSCs as a potential application of bone formation in further animal experiments.
Topics: Animals; Bone Regeneration; Bone and Bones; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Osteogenesis
PubMed: 34215342
DOI: 10.1186/s13287-021-02456-w -
International Journal of Nanomedicine 2020Bone regeneration remains a great clinical challenge. Two-dimensional materials, especially graphene and its derivative graphene oxide, have been widely used for bone... (Review)
Review
Bone regeneration remains a great clinical challenge. Two-dimensional materials, especially graphene and its derivative graphene oxide, have been widely used for bone regeneration. Since its discovery in 2014, black phosphorus (BP) nanomaterials including BP nanosheets and BP quantum dots have attracted considerable scientific attention and are considered as prospective graphene substitutes. BP nanomaterials exhibit numerous advantages such as excellent optical and mechanical properties, electrical conductivity, excellent biocompatibility, and good biodegradation, all of which make them particularly attractive in biomedicine. In this review, we comprehensively summarize recent advances of BP-based nanomaterials in bone regeneration. The advantages are reviewed, the different synthesis methods of BP are summarized, and the applications to promote bone regeneration are highlighted. Finally, the existing challenges and perspectives of BP in bone regeneration are briefly discussed.
Topics: Animals; Biocompatible Materials; Bone Regeneration; Graphite; Humans; Nanostructures; Phosphorus; Quantum Dots
PubMed: 32273701
DOI: 10.2147/IJN.S246336 -
Journal of Molecular Endocrinology Jul 2018Glucocorticoid hormones (GCs) have profound effects on bone metabolism. Via their nuclear hormone receptor - the GR - they act locally within bone cells and modulate... (Review)
Review
Glucocorticoid hormones (GCs) have profound effects on bone metabolism. Via their nuclear hormone receptor - the GR - they act locally within bone cells and modulate their proliferation, differentiation, and cell death. Consequently, high glucocorticoid levels - as present during steroid therapy or stress - impair bone growth and integrity, leading to retarded growth and glucocorticoid-induced osteoporosis, respectively. Because of their profound impact on the immune system and bone cell differentiation, GCs also affect bone regeneration and fracture healing. The use of conditional-mutant mouse strains in recent research provided insights into the cell-type-specific actions of the GR. However, despite recent advances in system biology approaches addressing GR genomics in general, little is still known about the molecular mechanisms of GCs and GR in bone cells. Here, we review the most recent findings on the molecular mechanisms of the GR in general and the known cell-type-specific actions of the GR in mesenchymal cells and their derivatives as well as in osteoclasts during bone homeostasis, GC excess, bone regeneration and fracture healing.
Topics: Animals; Bone Regeneration; Fracture Healing; Glucocorticoids; Humans; Osteoblasts; Osteoclasts; Receptors, Glucocorticoid; Skeleton
PubMed: 29588427
DOI: 10.1530/JME-18-0024 -
Advanced Science (Weinheim,... Nov 2023Geometry and angles play crucial roles in cellular processes; however, its mechanisms of regulation remain unclear. In this study, a series of three dimensional...
Geometry and angles play crucial roles in cellular processes; however, its mechanisms of regulation remain unclear. In this study, a series of three dimensional (3D)-printed microfibers with different geometries is constructed using a near-field electrostatic printing technique to investigate the regulatory mechanisms of geometry on stem cell function and bone regeneration. The scaffolds precisely mimicked cell dimensions with high porosity and interoperability. Compared with other spatial topography angles, microfibers with a 90° topology can significantly promote the expression of osteogenic gene proteins in bone marrow-derived mesenchymal stem cells (BMSCs). The effects of different spatial structures on the expression profiles of BMSCs differentiation genes are correlated and validated using microRNA sequencing. Enrichment analysis shows that the 90° microfibers promoted osteogenesis in BMSCs by significantly upregulating miR-222-5p/cbfb/Runx2 expression. The ability of the geometric architecture to promote bone regeneration, as assessed using the cranial defect model, demonstrates that the 90° fiber scaffolds significantly promote new bone regeneration and neovascular neural network formation. This study is the first to elucidate the relationship between angular geometry and cellular gene expression, contributing significantly to the understanding of how geometric architecture can promote stem cell differentiation, proliferation, and function for structural bone regeneration.
Topics: Bone Regeneration; Osteogenesis; Cell Differentiation; Stem Cells; Gene Expression
PubMed: 37775309
DOI: 10.1002/advs.202304111 -
International Journal of Molecular... Jul 2021Bone damage leading to bone loss can arise from a wide range of causes, including those intrinsic to individuals such as infections or diseases with metabolic... (Review)
Review
Bone damage leading to bone loss can arise from a wide range of causes, including those intrinsic to individuals such as infections or diseases with metabolic (diabetes), genetic (osteogenesis imperfecta), and/or age-related (osteoporosis) etiology, or extrinsic ones coming from external insults such as trauma or surgery. Although bone tissue has an intrinsic capacity of self-repair, large bone defects often require anabolic treatments targeting bone formation process and/or bone grafts, aiming to restore bone loss. The current bone surrogates used for clinical purposes are autologous, allogeneic, or xenogeneic bone grafts, which although effective imply a number of limitations: the need to remove bone from another location in the case of autologous transplants and the possibility of an immune rejection when using allogeneic or xenogeneic grafts. To overcome these limitations, cutting edge therapies for skeletal regeneration of bone defects are currently under extensive research with promising results; such as those boosting endogenous bone regeneration, by the stimulation of host cells, or the ones driven exogenously with scaffolds, biomolecules, and mesenchymal stem cells as key players of bone healing process.
Topics: Animals; Bone Regeneration; Bone and Bones; Graft Rejection; Humans; Mesenchymal Stem Cells; Osteogenesis; Tissue Scaffolds; Wound Healing
PubMed: 34299344
DOI: 10.3390/ijms22147724 -
Journal of Materials Chemistry. B Mar 2020Surface modification of orthopedic and dental implants has been demonstrated to be an effective strategy to accelerate bone healing at early implantation times. Among... (Review)
Review
Surface modification of orthopedic and dental implants has been demonstrated to be an effective strategy to accelerate bone healing at early implantation times. Among the different alternatives, coating implants with a layer of hydroxyapatite (HAp) is one of the most used techniques, due to its excellent biocompatibility and osteoconductive behavior. The composition and crystalline structure of HAp allow for numerous ionic substitutions that provide added value, such as antibiotic properties or osteoinduction. In this article, we will review and critically analyze the most important advances in the field of substituted hydroxyapatite coatings. In recent years substituted HAp coatings have been deposited not only on orthopedic prostheses and dental implants, but also on macroporous scaffolds, thus expanding their applications towards bone regeneration therapies. Besides, the capability of substituted HAps to immobilize proteins and growth factors by non-covalent interactions has opened new possibilities for preparing hybrid coatings that foster bone healing processes. Finally, the most important in vivo outcomes will be discussed to understand the prospects of substituted HAp coatings from a clinical point of view.
Topics: Animals; Bone Regeneration; Bone Substitutes; Coated Materials, Biocompatible; Dental Implants; Durapatite; Humans; Materials Testing
PubMed: 32065184
DOI: 10.1039/c9tb02710f -
BioMed Research International 2015
Topics: Animals; Bone Regeneration; Humans; Tooth
PubMed: 26491694
DOI: 10.1155/2015/934525