scholarly journals Mice Lacking the Calcitonin Receptor Do Not Display Improved Bone Healing

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2304
Author(s):  
Jessika Appelt ◽  
Serafeim Tsitsilonis ◽  
Ellen Otto ◽  
Denise Jahn ◽  
Paul Köhli ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Bone Healing ◽  
Bone Repair ◽  
Treatment Options ◽  
Healing Process ◽  
Surgical Techniques ◽  
Calcitonin Receptor ◽  
Normal Bone ◽  
Prolonged Immobilization ◽  
Deficient Mice

Despite significant advances in surgical techniques, treatment options for impaired bone healing are still limited. Inadequate bone regeneration is not only associated with pain, prolonged immobilization and often multiple revision surgeries, but also with high socioeconomic costs, underlining the importance of a detailed understanding of the bone healing process. In this regard, we previously showed that mice lacking the calcitonin receptor (CTR) display increased bone formation mediated through the increased osteoclastic secretion of sphingosine-1-phosphate (S1P), an osteoanabolic molecule promoting osteoblast function. Although strong evidence is now available for the crucial role of osteoclast-to-osteoblast coupling in normal bone hemostasis, the relevance of this paracrine crosstalk during bone regeneration is unknown. Therefore, our study was designed to test whether increased osteoclast-to-osteoblast coupling, as observed in CTR-deficient mice, may positively affect bone repair. In a standardized femoral osteotomy model, global CTR-deficient mice displayed no alteration in radiologic callus parameters. Likewise, static histomorphometry demonstrated moderate impairment of callus microstructure and normal osseous bridging of osteotomy ends. In conclusion, bone regeneration is not accelerated in CTR-deficient mice, and contrary to its osteoanabolic action in normal bone turnover, osteoclast-to-osteoblast coupling specifically involving the CTR-S1P axis, may only be of minor relevance during bone healing.

scholarly journals Bovine-Derived Xenografts Immobilized With Cryopreserved Stem Cells From Human Adipose and Dental Pulp Tissues Promote Bone Regeneration: A Radiographic and Histological Study

2021 ◽  
Vol 9 ◽  
Author(s):  
Yu Zhu ◽  
Shi-min Wei ◽  
Kai-xiao Yan ◽  
Ying-xin Gu ◽  
Hong-chang Lai ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Regeneration ◽  
Bone Healing ◽  
Dental Pulp ◽  
Bone Repair ◽  
Histological Study ◽  
Healing Process ◽  
Combined Treatment ◽  
Differentiation Potential

Adipose tissue-derived stem cells (ADSCs) and dental pulp stem cells (DPSCs) have become promising sources for bone tissue engineering. Our study aimed at evaluating bone regeneration potential of cryopreserved ADSCs and DPSCs combined with bovine-derived xenografts with 10% porcine collagen. In vitro studies revealed that although DPSCs had higher proliferative abilities, ADSCs exhibited greater mineral depositions and higher osteogenic-related gene expression, indicating better osteogenic differentiation potential of ADSCs. After applying cryopreserved ADSCs and DPSCs in a critical-sized calvarial defect model, both cryopreserved mesenchymal stem cells significantly improved bone volume density and new bone area at 2, 4, and 8 weeks. Furthermore, the combined treatment with ADSCs and xenografts was more efficient in enhancing bone repair processes compared to combined treatment with DPCSs at all-time points. We also evaluated the sequential early bone healing process both histologically and radiographically, confirming a high agreement between these two methods. Based on these results, we propose grafting of the tissue-engineered construct seeded with cryopreserved ADSCs as a useful strategy in accelerating bone healing processes.

scholarly journals Sodium-DNA for Bone Tissue Regeneration: An Experimental Study in Rat Calvaria

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Barbara Buffoli ◽  
Gaia Favero ◽  
Elisa Borsani ◽  
Ramon Boninsegna ◽  
Guido Sancassani ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Bone Tissue ◽  
Tissue Regeneration ◽  
Bone Healing ◽  
Healing Process ◽  
Maxillofacial Surgery ◽  
Surgical Techniques ◽  
Bone Tissue Regeneration ◽  
Fast Bone ◽  
Rat Calvarial Defect

Surgical techniques in dental and maxillofacial surgery request fast bone tissue regeneration, so there is a significant need to improve therapy for bone regeneration. Several studies have recently underlined the importance of nucleotides and nucleosides to increase cell proliferation and activity; in particular, the ability of polydeoxyribonucleotide (PDRN) to induce growth and activity of human osteoblasts was demonstrated. Sodium-DNA is the deoxyribonucleic acid (DNA) extracted from the gonadic tissue of male sturgeon and then purified, depolymerized, and neutralized with sodium hydroxide. To date, there are no evidences about the use of Sodium-DNA for bone tissue regeneration. Consequently, our question is about the efficacy of Sodium-DNA in bone healing. For testing the role of Sodium-DNA in bone healing we used a rat calvarial defect model. Sodium-DNA at different concentrations used alone or in association with Fibrin and/or Bio-Oss was used for healing treatments and the bone healing process was evaluated by histomorphometric and immunohistochemical analyses. Our results suggested a positive effect of Sodium-DNA in bone regeneration, providing a useful protocol and a model for the future clinical evaluation of its osteogenic properties.

scholarly journals Zn-Containing Membranes for Guided Bone Regeneration in Dentistry

Polymers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1797
Author(s):  
Manuel Toledano ◽  
Marta Vallecillo-Rivas ◽  
María T. Osorio ◽  
Esther Muñoz-Soto ◽  
Manuel Toledano-Osorio ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Bone Regeneration ◽  
Bone Healing ◽  
Bone Repair ◽  
Complex Modulus ◽  
Bacterial Colonization ◽  
Guided Bone Regeneration ◽  
M2 Macrophage

Barrier membranes are employed in guided bone regeneration (GBR) to facilitate bone in-growth. A bioactive and biomimetic Zn-doped membrane with the ability to participate in bone healing and regeneration is necessary. The aim of the present study is to state the effect of doping the membranes for GBR with zinc compounds in the improvement of bone regeneration. A literature search was conducted using electronic databases, such as PubMed, MEDLINE, DIMDI, Embase, Scopus and Web of Science. A narrative exploratory review was undertaken, focusing on the antibacterial effects, physicochemical and biological properties of Zn-loaded membranes. Bioactivity, bone formation and cytotoxicity were analyzed. Microstructure and mechanical properties of these membranes were also determined. Zn-doped membranes have inhibited in vivo and in vitro bacterial colonization. Zn-alloy and Zn-doped membranes attained good biocompatibility and were found to be non-toxic to cells. The Zn-doped matrices showed feasible mechanical properties, such as flexibility, strength, complex modulus and tan delta. Zn incorporation in polymeric membranes provided the highest regenerative efficiency for bone healing in experimental animals, potentiating osteogenesis, angiogenesis, biological activity and a balanced remodeling. Zn-loaded membranes doped with SiO2 nanoparticles have performed as bioactive modulators provoking an M2 macrophage increase and are a potential biomaterial for promoting bone repair. Zn-doped membranes have promoted pro-healing phenotypes.

scholarly journals Bone Regeneration Assessment of Polycaprolactone Membrane on Critical-Size Defects in Rat Calvaria

Membranes ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 124
Author(s):  
Ana Paula Farnezi Bassi ◽  
Vinícius Ferreira Bizelli ◽  
Tamires Mello Francatti ◽  
Ana Carulina Rezende de Moares Ferreira ◽  
Járede Carvalho Pereira ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Bone Healing ◽  
Inflammatory Responses ◽  
Blood Clot ◽  
Healing Process ◽  
Male Rats ◽  
Control Group ◽  
Collagen Membrane ◽  
Large Area ◽  
Rat Calvaria

Biomaterials for use in guided bone regeneration (GBR) are constantly being investigated and developed to improve clinical outcomes. The present study aimed to comparatively evaluate the biological performance of different membranes during the bone healing process of 8 mm critical defects in rat calvaria in order to assess their influence on the quality of the newly formed bone. Seventy-two adult male rats were divided into three experimental groups (n = 24) based on the membranes used: the CG—membrane-free control group (only blood clot, negative control), BG—porcine collagen membrane group (Bio-Guide®, positive control), and the PCL—polycaprolactone (enriched with 5% hydroxyapatite) membrane group (experimental group). Histological and histometric analyses were performed at 7, 15, 30, and 60 days postoperatively. The quantitative data were analyzed by two-way ANOVA and Tukey’s test (p < 0.05). At 7 and 15 days, the inflammatory responses in the BG and PCL groups were significantly different (p < 0.05). The PCL group, at 15 days, showed a large area of newly formed bone. At 30 and 60 days postoperatively, the PCL and BG groups exhibited similar bone healing, including some specimens showing complete closure of the critical defect (p = 0.799). Thus, the PCL membrane was biocompatible, and has the potential to help with GBR procedures.

Role of Discoidin Domain Receptor 2 in Craniofacial Bone Regeneration

2021 ◽  
pp. 002203452110074
Author(s):  
A. Binrayes ◽  
C. Ge ◽  
F.F. Mohamed ◽  
R.T. Franceschi
Keyword(s):  
Bone Regeneration ◽  
Healing Process ◽  
Congenital Defects ◽  
Calvarial Bone ◽  
Discoidin Domain Receptor ◽  
Skeletal Defects ◽  
Discoidin Domain Receptor 2 ◽  
Collagen Receptor ◽  
Deficient Mice

Bone loss caused by trauma, neoplasia, congenital defects, or periodontal disease is a major cause of disability and human suffering. Skeletal progenitor cell–extracellular matrix interactions are critical for bone regeneration. Discoidin domain receptor 2 (DDR2), an understudied collagen receptor, plays an important role in skeletal development. Ddr2 loss-of-function mutations in humans and mice cause severe craniofacial and skeletal defects, including altered cranial shape, dwarfing, reduced trabecular and cortical bone, alveolar bone/periodontal defects, and altered dentition. However, the role of this collagen receptor in craniofacial regeneration has not been examined. To address this, calvarial subcritical-size defects were generated in wild-type (WT) and Ddr2-deficient mice. The complete bridging seen in WT controls at 4 wk postsurgery was not observed in Ddr2-deficient mice even after 12 wk. Quantitation of defect bone area by micro–computed tomography also revealed a 50% reduction in new bone volume in Ddr2-deficient mice. Ddr2 expression during calvarial bone regeneration was measured using Ddr2-LacZ knock-in mice. Expression was restricted to periosteal surfaces of uninjured calvarial bone and, after injury, was detected in select regions of the defect site by 3 d postsurgery and expanded during the healing process. The impaired bone healing associated with Ddr2 deficiency may be related to reduced osteoprogenitor or osteoblast cell proliferation and differentiation since knockdown/knockout of Ddr2 in a mesenchymal cell line and primary calvarial osteoblast cultures reduced osteoblast differentiation while Ddr2 overexpression was stimulatory. In conclusion, Ddr2 is required for cranial bone regeneration and may be a novel target for therapy.

Tissue Engineering Strategies to Promote Bone Repair

2018 ◽  
Vol 941 ◽  
pp. 2495-2500 ◽  
Author(s):  
Anne Margaux Collignon ◽  
Gaël Y. Rochefort
Keyword(s):  
Tissue Engineering ◽  
Bone Regeneration ◽  
Bone Tissue ◽  
Bone Healing ◽  
Bone Repair ◽  
Population Aging ◽  
Local Bone ◽  
Bone Injury ◽  
Autologous Bone

Bone displays an amazing capacity for endogenous self-remodeling. However, compromised bone healing and recovering is on the ascent because of population aging, expanding rate of bone injury and the clinical requirement for the advancement of elective choices to autologous bone unions. Current strategies, including biomolecules, cell treatments, biomaterials and diverse combinations of these, are presently created to encourage the vascularization and the engraftment of the grafts, to reproduce at last a bone tissue with similar properties and attributes of the local bone. In this review, we look through the current techniques that are right now created, utilizing biomolecules, cells and biomaterials, to initiate, coordinate and potentiate bone regeneration and healing after damage and further talk about the natural procedures related with this repair.

scholarly journals TRPM7 kinase-mediated immunomodulation in macrophage plays a central role in magnesium ion-induced bone regeneration

2020 ◽  
Author(s):  
Wei Qiao ◽  
Karen H.M. Wong ◽  
Jie Shen ◽  
Wenhao Wang ◽  
Jun Wu ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Bone Healing ◽  
Bone Repair ◽  
Transient Receptor Potential ◽  
Nuclear Accumulation ◽  
Magnesium Ion ◽  
Dependent Manner ◽  
Immune Microenvironment ◽  
Complex Biological Process ◽  
Macrophage Lineage

AbstractThe use of magnesium ion (Mg2+)-modified biomaterials in bone regeneration is a promising and cost-effective therapeutic. Despite the widespread observation on the osteogenic effects of Mg2+, the diverse roles played by Mg2+ in the complex biological process of bone healing have not been systematically dissected. Here, we reveal a previously unknown biphasic mode of action of Mg2+ in bone repair. In the early inflammation phase, Mg2+ primarily targets the monocyte-macrophage lineage to promote their recruitment, activation, and polarization. We showed that an increase in extracellular Mg2+ contributes to an upregulated expression of transient receptor potential cation channel member 7 (TRPM7) and a TRPM7-dependent influx of Mg2+ in the monocyte-macrophage lineage, resulting in the cleavage and nuclear accumulation of TRPM7-cleaved kinase fragments (M7CKs). This then triggers the phosphorylation of Histone H3 at serine 10, in a TRPM7-dependent manner at the promoters of inflammatory cytokines like IL-8, leading to the formation of a pro-osteogenic immune microenvironment. In the later active repair/remodeling phase of bone healing, however, continued exposure of Mg2+ and IL-8 leads to over activation of NF-κB signaling in macrophages, turning the immune microenvironment into pro-osteoclastogenesis. Moreover, the presence of Mg2+ at this stage also decelerates bone maturation through the suppression of hydroxyapatite precipitation. The negative effects of Mg2+ on osteogenesis can override the initial pro-osteogenic benefits of Mg2+, as we found prolonged delivery of Mg2+ compromises overall bone formation. Taken together, this study establishes a paradigm shift in understanding the diverse and multifaceted roles of Mg2+ in bone healing.

scholarly journals Current and Future Concepts for the Treatment of Impaired Fracture Healing

2019 ◽  
Vol 20 (22) ◽  
pp. 5805 ◽  
Author(s):  
Carsten W. Schlickewei ◽  
Holger Kleinertz ◽  
Darius M. Thiesen ◽  
Konrad Mader ◽  
Matthias Priemel ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Bone Regeneration ◽  
Treatment Options ◽  
Surgical Techniques ◽  
Therapeutic Approaches ◽  
Economic Implications ◽  
Complex Process ◽  
Number Of Patients ◽  
Evolutionarily Conserved ◽  
Future Concepts

Bone regeneration represents a complex process, of which basic biologic principles have been evolutionarily conserved over a broad range of different species. Bone represents one of few tissues that can heal without forming a fibrous scar and, as such, resembles a unique form of tissue regeneration. Despite a tremendous improvement in surgical techniques in the past decades, impaired bone regeneration including non-unions still affect a significant number of patients with fractures. As impaired bone regeneration is associated with high socio-economic implications, it is an essential clinical need to gain a full understanding of the pathophysiology and identify novel treatment approaches. This review focuses on the clinical implications of impaired bone regeneration, including currently available treatment options. Moreover, recent advances in the understanding of fracture healing are discussed, which have resulted in the identification and development of novel therapeutic approaches for affected patients.

Evaluation of the Bone Healing Process Utilizing Platelet-Rich Plasma Activated by Thrombin and Calcium Chloride: A Histologic Study in Rabbit Calvaria

2013 ◽  
Vol 39 (1) ◽  
pp. 14-21 ◽  
Author(s):  
Walter Betoni-Junior ◽  
Paula Dechichi ◽  
Jônatas Caldeira Esteves ◽  
Darceny Zanetta-Barbosa ◽  
Aparecido Eurípedes Onório Magalhães
Keyword(s):  
Bone Graft ◽  
Calcium Chloride ◽  
Bone Healing ◽  
Bone Repair ◽  
Platelet Rich Plasma ◽  
Healing Process ◽  
Bone Defects ◽  
Histomorphometric Analysis ◽  
Histologic Study ◽  
Vascularized Bone

To evaluate the bone healing of defects filled with particulate bone graft in combination with platelet-rich plasma (PRP), added with a mixture of calcium chloride and thrombin or just calcium chloride. Two 5-mm bone defects were created in the calvaria of 24 rabbits. Each defect was filled with particulate bone graft and PRP. In one defect the PRP was activated by a mixture of calcium chloride and thrombin; in the other, PRP was activated by calcium chloride only. The animals were euthanized 1, 2, 4, and 8 weeks after the surgeries, and the calvaria was submitted to histologic processing for histomorphometric analysis. The qualitative analysis has shown that both defects presented the same histologic characteristics so that a better organized, more mature, and well-vascularized bone tissue was noticed in the eighth week. A good bone repair was achieved using either the mixture of calcium chloride and thrombin or the calcium chloride alone as a restarting agent of the coagulation process.

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