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Cell Jan 2023Blood and lymphatic vessels form a versatile transport network and provide inductive signals to regulate tissue-specific functions. Blood vessels in bone regulate...
Blood and lymphatic vessels form a versatile transport network and provide inductive signals to regulate tissue-specific functions. Blood vessels in bone regulate osteogenesis and hematopoiesis, but current dogma suggests that bone lacks lymphatic vessels. Here, by combining high-resolution light-sheet imaging and cell-specific mouse genetics, we demonstrate presence of lymphatic vessels in mouse and human bones. We find that lymphatic vessels in bone expand during genotoxic stress. VEGF-C/VEGFR-3 signaling and genotoxic stress-induced IL6 drive lymphangiogenesis in bones. During lymphangiogenesis, secretion of CXCL12 from proliferating lymphatic endothelial cells is critical for hematopoietic and bone regeneration. Moreover, lymphangiocrine CXCL12 triggers expansion of mature Myh11 CXCR4 pericytes, which differentiate into bone cells and contribute to bone and hematopoietic regeneration. In aged animals, such expansion of lymphatic vessels and Myh11-positive cells in response to genotoxic stress is impaired. These data suggest lymphangiogenesis as a therapeutic avenue to stimulate hematopoietic and bone regeneration.
Topics: Aged; Animals; Humans; Mice; Bone Regeneration; Endothelial Cells; Lymphangiogenesis; Lymphatic Vessels
PubMed: 36669473
DOI: 10.1016/j.cell.2022.12.031 -
Nature Reviews. Rheumatology Oct 2021Blood vessels form a versatile transport network that is best known for its critical roles in processes such as tissue oxygenation, metabolism and immune surveillance.... (Review)
Review
Blood vessels form a versatile transport network that is best known for its critical roles in processes such as tissue oxygenation, metabolism and immune surveillance. The vasculature also provides local, often organ-specific, molecular signals that control the behaviour of other cell types in their vicinity during development, homeostasis and regeneration, and also in disease processes. In the skeletal system, the local vasculature is actively involved in both bone formation and resorption. In addition, blood vessels participate in inflammatory processes and contribute to the pathogenesis of diseases that affect the joints, such as rheumatoid arthritis and osteoarthritis. This Review summarizes the current understanding of the architecture, angiogenic growth and functional properties of the bone vasculature. The effects of ageing and pathological conditions, including arthritis and osteoporosis, are also discussed.
Topics: Aging; Animals; Arthritis; Bone Development; Bone Diseases; Bone Regeneration; Bone and Bones; Chondrocytes; Endothelium, Vascular; Fractures, Bone; Homeostasis; Humans; Joint Diseases; Macrophages; Mice; Neovascularization, Pathologic; Neovascularization, Physiologic; Osteoblasts; Osteogenesis; Osteoporosis; Receptor Cross-Talk; Synoviocytes
PubMed: 34480164
DOI: 10.1038/s41584-021-00682-3 -
Experimental & Molecular Medicine Nov 2022The mammalian skeletal system is densely innervated by both neural and vascular networks. Peripheral nerves in the skeleton include sensory and sympathetic nerves. The... (Review)
Review
The mammalian skeletal system is densely innervated by both neural and vascular networks. Peripheral nerves in the skeleton include sensory and sympathetic nerves. The crosstalk between skeletal and neural tissues is critical for skeletal development and regeneration. The cellular processes of osteogenesis and angiogenesis are coupled in both physiological and pathophysiological contexts. The cellular and molecular regulation of osteogenesis and angiogenesis have yet to be fully defined. This review will provide a detailed characterization of the regulatory role of nerves and blood vessels during bone regeneration. Furthermore, given the importance of the spatial relationship between nerves and blood vessels in bone, we discuss neurovascular coupling during physiological and pathological bone formation. A better understanding of the interactions between nerves and blood vessels will inform future novel therapeutic neural and vascular targeting for clinical bone repair and regeneration.
Topics: Animals; Neurovascular Coupling; Vascular Endothelial Growth Factor A; Bone Regeneration; Osteogenesis; Bone and Bones; Neovascularization, Physiologic; Mammals
PubMed: 36446849
DOI: 10.1038/s12276-022-00899-6 -
Marine Drugs Jan 2022Marine organisms harbor numerous bioactive substances that can be utilized in the pharmaceutical and cosmetic industries. Scientific research on various applications of... (Review)
Review
Marine organisms harbor numerous bioactive substances that can be utilized in the pharmaceutical and cosmetic industries. Scientific research on various applications of collagen extracted from these organisms has become increasingly prevalent. Marine collagen can be used as a biomaterial because it is water soluble, metabolically compatible, and highly accessible. Upon review of the literature, it is evident that marine collagen is a versatile compound capable of healing skin injuries of varying severity, as well as delaying the natural human aging process. From in vitro to in vivo experiments, collagen has demonstrated its ability to invoke keratinocyte and fibroblast migration as well as vascularization of the skin. Additionally, marine collagen and derivatives have proven beneficial and useful for both osteoporosis and osteoarthritis prevention and treatment. Other bone-related diseases may also be targeted by collagen, as it is capable of increasing bone mineral density, mineral deposition, and importantly, osteoblast maturation and proliferation. In this review, we demonstrate the advantages of marine collagen over land animal sources and the biomedical applications of marine collagen related to bone and skin damage. Finally, some limitations of marine collagen are briefly discussed.
Topics: Animals; Aquatic Organisms; Biocompatible Materials; Bone Regeneration; Collagen; Skin Aging; Wound Healing
PubMed: 35049916
DOI: 10.3390/md20010061 -
Biomaterials Apr 2022Embryogenic developmental processes involve a tightly controlled regulation between mechanical forces and biochemical cues such as growth factors, matrix proteins, and... (Review)
Review
Embryogenic developmental processes involve a tightly controlled regulation between mechanical forces and biochemical cues such as growth factors, matrix proteins, and cytokines. This interplay remains essential in the mature body, with aberrant pathway signaling leading to abnormalities such as atherosclerosis in the cardiovascular system, inflammation in tendon tissue, or osteoporosis in the bone. The aim of bone regenerative strategies is to develop tools and procedures that will harness the body's own self-repair ability in order to successfully regenerate even very large and complex bone defects and restore normal function. To achieve this, understanding pathways that govern processes of progenitor differentiation towards the osteogenic lineages, their phenotypical maintenance, and the construction of functional bone tissue is imperative to subsequently develop regenerative therapies that mimic these processes. While a body of literature exists that describes how biochemical stimuli guide cell behavior in the culture dish, due to the lack of an appropriate mechanical environment, these signals are often insufficient or inappropriate for achieving a desirable response in the body. Moreover, bone regenerative therapies rarely rely on a biochemical stimulus, such as a growth factor alone, and instead often comprise a carrier biomaterial that introduces a very different microenvironment from that of a cell culture dish. Therefore, in this review, we discuss which biomaterials elicit or influence pathways relevant for bone regeneration and describe mechanisms behind these effects, with the aim to inspire the development of novel, more effective bone regenerative therapies.
Topics: Biocompatible Materials; Bone Regeneration; Bone and Bones; Cell Differentiation; Osteogenesis; Tissue Engineering
PubMed: 35231787
DOI: 10.1016/j.biomaterials.2022.121431 -
Materials Science & Engineering. C,... Nov 2021To induce bone regeneration there is a complex cascade of growth factors. Growth factors such as recombinant BMP-2, BMP-7, and PDGF are FDA-approved therapies in bone... (Review)
Review
To induce bone regeneration there is a complex cascade of growth factors. Growth factors such as recombinant BMP-2, BMP-7, and PDGF are FDA-approved therapies in bone regeneration. Although, BMP shows promising results as being an alternative to autograft, it also has its own downfalls. BMP-2 has many adverse effects such as inflammatory complications such as massive soft-tissue swelling that can compromise a patient's airway, ectopic bone formation, and tumor formation. BMP-2 may also be advantageous for patients not willing to give up smoking as it shows bone regeneration success with smokers. BMP-7 is no longer an option for bone regeneration as it has withdrawn off the market. PDGF-BB grafts in studies have shown PDGF had similar fusion rates to autologous grafts and fewer adverse effects. There is also an FDA-approved bioactive molecule for bone regeneration, a peptide P-15. P-15 was found to be effective, safe, and have similar outcomes to autograft at 2 years post-op for cervical radiculopathy due to cervical degenerative disc disease. Growth factors and bioactive molecules show some promising results in bone regeneration, although more research is needed to avoid their adverse effects and learn about the long-term effects of these therapies. There is a need of a bone regeneration method of similar quality of an autograft that is osteoconductive, osteoinductive, and osteogenic. This review covers all FDA-approved bone regeneration therapies such as the "gold standard" autografts, allografts, synthetic bone grafts, and the newer growth factors/bioactive molecules. It also covers international bone grafts not yet approved in the United States and upcoming technologies in bone grafts.
Topics: Bone Morphogenetic Protein 2; Bone Regeneration; Bone Substitutes; Bone Transplantation; Cervical Vertebrae; Humans; Intervertebral Disc Degeneration
PubMed: 34702541
DOI: 10.1016/j.msec.2021.112466 -
International Journal of Molecular... Nov 2022Guided bone regeneration (GBR) has become a clinically standard modality for the treatment of localized jawbone defects. Barrier membranes play an important role in this... (Review)
Review
Guided bone regeneration (GBR) has become a clinically standard modality for the treatment of localized jawbone defects. Barrier membranes play an important role in this process by preventing soft tissue invasion outgoing from the mucosa and creating an underlying space to support bone growth. Different membrane types provide different biological mechanisms due to their different origins, preparation methods and structures. Among them, collagen membranes have attracted great interest due to their excellent biological properties and desired bone regeneration results to non-absorbable membranes even without a second surgery for removal. This work provides a comparative summary of common barrier membranes used in GBR, focusing on recent advances in collagen membranes and their biological mechanisms. In conclusion, the review article highlights the biological and regenerative properties of currently available barrier membranes with a particular focus on bioresorbable collagen-based materials. In addition, the advantages and disadvantages of these biomaterials are highlighted, and possible improvements for future material developments are summarized.
Topics: Guided Tissue Regeneration, Periodontal; Membranes, Artificial; Bone Regeneration; Collagen; Biocompatible Materials; Polytetrafluoroethylene; Guided Tissue Regeneration
PubMed: 36499315
DOI: 10.3390/ijms232314987 -
Materials Science & Engineering. C,... May 2020The goal of a biomaterial is to support the bone tissue regeneration process at the defect site and eventually degrade in situ and get replaced with the newly generated... (Review)
Review
The goal of a biomaterial is to support the bone tissue regeneration process at the defect site and eventually degrade in situ and get replaced with the newly generated bone tissue. Nanocomposite biomaterials are a relatively new class of materials that incorporate a biopolymeric and biodegradable matrix structure with bioactive and easily resorbable fillers which are nano-sized. This article is a review of a few polymeric nanocomposite biomaterials which are potential candidates for bone tissue regeneration. These nanocomposites have been broadly classified into two groups viz. natural and synthetic polymer based. Natural polymer-based nanocomposites include materials fabricated through reinforcement of nanoparticles and/or nanofibers in a natural polymer matrix. Several widely used natural biopolymers, such as chitosan (CS), collagen (Col), cellulose, silk fibroin (SF), alginate, and fucoidan, have been reviewed regarding their present investigation on the incorporation of nanomaterial, biocompatibility, and tissue regeneration. Synthetic polymer-based nanocomposites that have been covered in this review include polycaprolactone (PCL), poly (lactic-co-glycolic) acid (PLGA), polyethylene glycol (PEG), poly (lactic acid) (PLA), and polyurethane (PU) based nanocomposites. An array of nanofillers, such as nano hydroxyapatite (nHA), nano zirconia (nZr), nano silica (nSi), silver nano particles (AgNPs), nano titanium dioxide (nTiO), graphene oxide (GO), that is used widely across the bone tissue regeneration research platform are included in this review with respect to their incorporation into a natural and/or synthetic polymer matrix. The influence of nanofillers on cell viability, both in vitro and in vivo, along with cytocompatibility and new tissue generation has been encompassed in this review. Moreover, nanocomposite material characterization using some commonly used analytical techniques, such as electron microscopy, spectroscopy, diffraction patterns etc., has been highlighted in this review. Biomaterial physical properties, such as pore size, porosity, particle size, and mechanical strength which strongly influences cell attachment, proliferation, and subsequent tissue growth has been covered in this review. This review has been sculptured around a case by case basis of current research that is being undertaken in the field of bone regeneration engineering. The nanofillers induced into the polymeric matrix render important properties, such as large surface area, improved mechanical strength as well as stability, improved cell adhesion, proliferation, and cell differentiation. The selection of nanocomposites is thus crucial in the analysis of viable treatment strategies for bone tissue regeneration for specific bone defects such as craniofacial defects. The effects of growth factor incorporation on the nanocomposite for controlling new bone generation are also important during the biomaterial design phase.
Topics: Animals; Biocompatible Materials; Bone Regeneration; Bone and Bones; Humans; Nanocomposites; Polymers; Tissue Engineering; Tissue Scaffolds
PubMed: 32204012
DOI: 10.1016/j.msec.2020.110698 -
International Journal of Medical... 2021Bone is an active tissue, being constantly renewed in healthy individuals with participation of the immune system to a large extent. Any imbalance between the processes... (Review)
Review
Bone is an active tissue, being constantly renewed in healthy individuals with participation of the immune system to a large extent. Any imbalance between the processes of bone formation and bone resorption is linked to various inflammatory bone diseases. The immune system plays an important role in tissue formation and bone resorption. Recently, many studies have demonstrated complex interactions between the immune and skeletal systems. Both of immune cells and cytokines contribute to the regulation of bone homeostasis, and bone cells, including osteoblasts, osteoclasts, osteocytes, also influence the cellular functions of immune cells. These crosstalk mechanisms between the bone and immune system finally emerged, forming a new field of research called osteoimmunology. Therefore, the immune microenvironment is crucial in determining the speed and outcome of bone healing, repair, and regeneration. In this review, we summarise the role of the immune microenvironment in bone regeneration from the aspects of immune cells and immune cytokines. The elucidation of immune mechanisms involved in the process of bone regeneration would provide new therapeutic targets for improving the curative effects of bone injury treatment.
Topics: Animals; Bone Regeneration; Bone Remodeling; Bone and Bones; Cellular Microenvironment; Humans; Immune System; Osteoblasts; Osteoclasts; Osteocytes
PubMed: 34790042
DOI: 10.7150/ijms.61080 -
Advanced Drug Delivery Reviews Jul 2021Bone regenerative engineering provides a great platform for bone tissue regeneration covering cells, growth factors and other dynamic forces for fabricating scaffolds.... (Review)
Review
Bone regenerative engineering provides a great platform for bone tissue regeneration covering cells, growth factors and other dynamic forces for fabricating scaffolds. Diversified biomaterials and their fabrication methods have emerged for fabricating patient specific bioactive scaffolds with controlled microstructures for bridging complex bone defects. The goal of this review is to summarize the points of scaffold design as well as applications for bone regeneration based on both electrospinning and 3D bioprinting. It first briefly introduces biological characteristics of bone regeneration and summarizes the applications of different types of material and the considerations for bone regeneration including polymers, ceramics, metals and composites. We then discuss electrospinning nanofibrous scaffold applied for the bone regenerative engineering with various properties, components and structures. Meanwhile, diverse design in the 3D bioprinting scaffolds for osteogenesis especially in the role of drug and bioactive factors delivery are assembled. Finally, we discuss challenges and future prospects in the development of electrospinning and 3D bioprinting for osteogenesis and prominent strategies and directions in future.
Topics: Animals; Biocompatible Materials; Bioprinting; Bone Regeneration; Humans; Nanofibers; Osteogenesis; Printing, Three-Dimensional; Regenerative Medicine; Tissue Engineering; Tissue Scaffolds
PubMed: 33991588
DOI: 10.1016/j.addr.2021.05.007