scholarly journals Smoothened agonist sterosome immobilized hybrid scaffold for bone regeneration

2020 ◽  
Vol 6 (17) ◽  
pp. eaaz7822 ◽  
Author(s):  
Chung-Sung Lee ◽  
Soyon Kim ◽  
Jiabing Fan ◽  
Hee Sook Hwang ◽  
Tara Aghaloo ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Cell Fate ◽  
Bone Repair ◽  
Drug Loading ◽  
Three Dimensional ◽  
Hedgehog Pathway ◽  
Hybrid Scaffold ◽  
Synergistic Activation ◽  
Bioactive Agents ◽  
Osteoinductive Property

Biomaterial delivery of bioactive agents and manipulation of stem cell fate are an attractive approach to promote tissue regeneration. Here, smoothened agonist sterosome is developed using small-molecule activators [20S-hydroxycholesterol (OHC) and purmorphamine (PUR)] of the smoothened protein in the hedgehog pathway as carrier and cargo. Sterosome presents inherent osteoinductive property even without drug loading. Sterosome is covalently immobilized onto three-dimensional scaffolds via a bioinspired polydopamine intermediate to fabricate a hybrid scaffold for bone regeneration. Sterosome-immobilized hybrid scaffold not only provides a favorable substrate for cell adhesion and proliferation but also delivers bioactive agents in a sustained and spatially targeted manner. Furthermore, this scaffold significantly improves osteogenic differentiation of bone marrow stem cells through OHC/PUR-mediated synergistic activation of the hedgehog pathway and also enhances bone repair in a mouse calvarial defect model. This system serves as a versatile biomaterial platform for many applications, including therapeutic delivery and endogenous regenerative medicine.

scholarly journals Solvent-Free Processing of Drug-Loaded Poly(ε-Caprolactone) Scaffolds with Tunable Macroporosity by Combination of Supercritical Foaming and Thermal Porogen Leaching

Polymers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 159
Author(s):  
Víctor Santos-Rosales ◽  
Inés Ardao ◽  
Leticia Goimil ◽  
Jose Luis Gomez-Amoza ◽  
Carlos A. García-González
Keyword(s):  
Bone Repair ◽  
Drug Loading ◽  
Ammonium Bicarbonate ◽  
Bone Diseases ◽  
Solvent Free ◽  
Bone Integration ◽  
Bioactive Agents ◽  
First Time ◽  
Supercritical Foaming ◽  
Foaming Technology

Demand of scaffolds for hard tissue repair increases due to a higher incidence of fractures related to accidents and bone-diseases that are linked to the ageing of the population. Namely, scaffolds loaded with bioactive agents can facilitate the bone repair by favoring the bone integration and avoiding post-grafting complications. Supercritical (sc-)foaming technology emerges as a unique solvent-free approach for the processing of drug-loadenu7d scaffolds at high incorporation yields. In this work, medicated poly(ε-caprolactone) (PCL) scaffolds were prepared by sc-foaming coupled with a leaching process to overcome problems of pore size tuning of the sc-foaming technique. The removal of the solid porogen (BA, ammonium bicarbonate) was carried out by a thermal leaching taking place at 37 °C and in the absence of solvents for the first time. Macroporous scaffolds with dual porosity (50–100 µm and 200–400 µm ranges) were obtained and with a porous structure directly dependent on the porogen content used. The processing of ketoprofen-loaded scaffolds using BA porogen resulted in drug loading yields close to 100% and influenced its release profile from the PCL matrix to a relevant clinical scenario. A novel solvent-free strategy has been set to integrate the incorporation of solid porogens in the sc-foaming of medicated scaffolds.

scholarly journals Application of a New Type of Natural Calcined Bone Repair Material Combined with Concentrated Growth Factors in Bone Regeneration in Rabbit Critical-Sized Calvarial Defect

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Xiaoyang Wang ◽  
Shuqing Tong ◽  
Shengyun Huang ◽  
Li Ma ◽  
Zhenxing Liu ◽  
...  
Keyword(s):  
Growth Factors ◽  
Bone Regeneration ◽  
Bone Defect ◽  
Bone Repair ◽  
Blank Group ◽  
Male Adult ◽  
Animal Group ◽  
Hybrid Scaffold ◽  
Concentrated Growth Factors ◽  
The Right

Purpose. This study is aimed at investigating bone regeneration in critical-sized defects in rabbit calvarium using a novel nano- (n-) hydroxyapatite hybrid scaffold with concentrated growth factors (CGFs). Methods. Twenty-four male adult rabbits were chosen to establish a critical-sized bone defect model and randomly divided into two groups. Two defects of 15 mm diameter each were created in the parietal bone of each animal. Group A had n-hydroxyapatite hybrid scaffold placed in the experimental defect on the right, and the left defect was unfilled as blank. Group B had hydroxyapatite hybrid scaffold mixed with CGF placed in the right defect and CGF on the left. Six animals in each group were sacrificed after 6 and 12 weeks. Cone-beam computed tomography system scanning and hematoxylin and eosin (HE) staining were used to detect osteogenesis within the defects. Results. The treatment with n-hydroxyapatite hybrid scaffold along with CGF resulted in a significantly higher amount of new bone at 6 and 12 weeks compared to the treatment with CGF alone and the controls. No apparent inflammation and foreign body reaction were observed through HE staining. Conclusions. The new synthesized n-hydroxyapatite hybrid scaffold and CGF can be applied for bone defect regeneration to promote the process to a certain extent.

scholarly journals An ECM-Mimicking, Mesenchymal Stem Cell-Embedded Hybrid Scaffold for Bone Regeneration

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Jozafina Haj ◽  
Tharwat Haj Khalil ◽  
Mizied Falah ◽  
Eyal Zussman ◽  
Samer Srouji
Keyword(s):  
Tissue Engineering ◽  
Extracellular Matrix ◽  
Bone Tissue Engineering ◽  
Bone Regeneration ◽  
Bone Tissue ◽  
Bone Repair ◽  
Dorsal Side ◽  
Human Mscs ◽  
Hybrid Scaffold

While biologically feasible, bone repair is often inadequate, particularly in cases of large defects. The search for effective bone regeneration strategies has led to the emergence of bone tissue engineering (TE) techniques. When integrating electrospinning techniques, scaffolds featuring randomly oriented or aligned fibers, characteristic of the extracellular matrix (ECM), can be fabricated. In parallel, mesenchymal stem cells (MSCs), which are capable of both self-renewing and differentiating into numerous tissue types, have been suggested to be a suitable option for cell-based tissue engineering therapies. This work aimed to create a novel biocompatible hybrid scaffold composed of electrospun polymeric nanofibers combined with osteoconductive ceramics, loaded with human MSCs, to yield a tissue-like construct to promote in vivo bone formation. Characterization of the cell-embedded scaffolds demonstrated their resemblance to bone tissue extracellular matrix, on both micro- and nanoscales and MSC viability and integration within the electrospun nanofibers. Subcutaneous implantation of the cell-embedded scaffolds in the dorsal side of mice led to new bone, muscle, adipose, and connective tissue formation within 8 weeks. This hybrid scaffold may represent a step forward in the pursuit of advanced bone tissue engineering scaffolds.

Drug‐loading three‐dimensional scaffolds based on hydroxyapatite‐sodium alginate for bone regeneration

2020 ◽  
Vol 109 (2) ◽  
pp. 219-231
Author(s):  
Tingting Liang ◽  
Jingwen Wu ◽  
Fuyao Li ◽  
Zhu Huang ◽  
Yixing Pi ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Sodium Alginate ◽  
Drug Loading ◽  
Three Dimensional

Modern approaches on stem cells and scaffolding technology for osteogenic differentiation and regeneration

2021 ◽  
pp. 153537022110529
Author(s):  
Shivaani Kirankumar ◽  
Narasimman Gurusamy ◽  
Sheeja Rajasingh ◽  
Vinoth Sigamani ◽  
Jayavardini Vasanthan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Regeneration ◽  
Bone Repair ◽  
Molecular Mechanisms ◽  
Bone Cells ◽  
Three Dimensional ◽  
Non Union ◽  
Cell Based Therapy ◽  
Osteogenic Factors

The process of bone repair has always been a natural mystery. Although bones do repair themselves, supplemental treatment is required for the initiation of the self-regeneration process. Predominantly, surgical procedures are employed for bone regeneration. Recently, cell-based therapy for bone regeneration has proven to be more effective than traditional methods, as it eliminates the immune risk and painful surgeries. In clinical trials, various stem cells, especially mesenchymal stem cells, have shown to be more efficient for the treatment of several bone-related diseases, such as non-union fracture, osteogenesis imperfecta, osteosarcoma, and osteoporosis. Furthermore, the stem cells grown in a suitable three-dimensional scaffold support were found to be more efficient for osteogenesis. It has been shown that the three-dimensional bioscaffolds support and simulate an in vivo environment, which helps in differentiation of stem cells into bone cells. Bone regeneration in patients with bone disorders can be improved through modification of stem cells with several osteogenic factors or using stem cells as carriers for osteogenic factors. In this review, we focused on the various types of stem cells and scaffolds that are being used for bone regeneration. In addition, the molecular mechanisms of various transcription factors, signaling pathways that support bone regeneration and the senescence of the stem cells, which limits bone regeneration, have been discussed.

In vitro Three Dimensional Scaffold-free Construct of Human Adipose-derived Stem Cells in Coculture with Endothelial Cells and Fibroblasts

2017 ◽  
Vol 68 (6) ◽  
pp. 1341-1344
Author(s):  
Grigore Berea ◽  
Gheorghe Gh. Balan ◽  
Vasile Sandru ◽  
Paul Dan Sirbu
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Endothelial Cells ◽  
Single Cell ◽  
Cell Line ◽  
Bone Repair ◽  
Umbilical Vein ◽  
Human Fibroblasts ◽  
Three Dimensional ◽  
Adipose Derived Stem Cells

Complex interactions between stem cells, vascular cells and fibroblasts represent the substrate of building microenvironment-embedded 3D structures that can be grafted or added to bone substitute scaffolds in tissue engineering or clinical bone repair. Human Adipose-derived Stem Cells (hASCs), human umbilical vein endothelial cells (HUVECs) and normal dermal human fibroblasts (NDHF) can be mixed together in three dimensional scaffold free constructs and their behaviour will emphasize their potential use as seeding points in bone tissue engineering. Various combinations of the aforementioned cell lines were compared to single cell line culture in terms of size, viability and cell proliferation. At 5 weeks, viability dropped for single cell line spheroids while addition of NDHF to hASC maintained the viability at the same level at 5 weeks Fibroblasts addition to the 3D construct of stem cells and endothelial cells improves viability and reduces proliferation as a marker of cell differentiation toward osteogenic line.

scholarly journals Rely on Each Other: DNA Binding Cooperativity Shapes p53 Functions in Tumor Suppression and Cancer Therapy

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2422
Author(s):  
Oleg Timofeev ◽  
Thorsten Stiewe
Keyword(s):  
Cancer Therapy ◽  
Dna Binding ◽  
Cell Fate ◽  
Tumor Suppression ◽  
Quaternary Structure ◽  
Three Dimensional ◽  
Structural Basis ◽  
Sequence Specificity ◽  
Cell Fate Decisions ◽  
Cancer Mutations

p53 is a tumor suppressor that is mutated in half of all cancers. The high clinical relevance has made p53 a model transcription factor for delineating general mechanisms of transcriptional regulation. p53 forms tetramers that bind DNA in a highly cooperative manner. The DNA binding cooperativity of p53 has been studied by structural and molecular biologists as well as clinical oncologists. These experiments have revealed the structural basis for cooperative DNA binding and its impact on sequence specificity and target gene spectrum. Cooperativity was found to be critical for the control of p53-mediated cell fate decisions and tumor suppression. Importantly, an estimated number of 34,000 cancer patients per year world-wide have mutations of the amino acids mediating cooperativity, and knock-in mouse models have confirmed such mutations to be tumorigenic. While p53 cancer mutations are classically subdivided into “contact” and “structural” mutations, “cooperativity” mutations form a mechanistically distinct third class that affect the quaternary structure but leave DNA contacting residues and the three-dimensional folding of the DNA-binding domain intact. In this review we discuss the concept of DNA binding cooperativity and highlight the unique nature of cooperativity mutations and their clinical implications for cancer therapy.

scholarly journals Mechanical Behavior of Hydroxyapatite-Chitosan Composite: Effect of Processing Parameters

Minerals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 213
Author(s):  
Hamid Ait Said ◽  
Hassan Noukrati ◽  
Hicham Ben Youcef ◽  
Ayoub Bayoussef ◽  
Hassane Oudadesse ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Compressive Strength ◽  
Mechanical Strength ◽  
Bone Repair ◽  
Mechanical Stability ◽  
Three Dimensional ◽  
Processing Parameters ◽  
Composite Effect ◽  
Solid Liquid ◽  
The Impact

Three-dimensional hydroxyapatite-chitosan (HA-CS) composites were formulated via solid-liquid technic and freeze-drying. The prepared composites had an apatitic nature, which was demonstrated by X-ray diffraction and Infrared spectroscopy analyses. The impact of the solid/liquid (S/L) ratio and the content and the molecular weight of the polymer on the composite mechanical strength was investigated. An increase in the S/L ratio from 0.5 to 1 resulted in an increase in the compressive strength for HA-CSL (CS low molecular weight: CSL) from 0.08 ± 0.02 to 1.95 ± 0.39 MPa and from 0.3 ± 0.06 to 2.40 ± 0.51 MPa for the HA-CSM (CS medium molecular weight: CSM). Moreover, the increase in the amount (1 to 5 wt%) and the molecular weight of the polymer increased the mechanical strength of the composite. The highest compressive strength value (up to 2.40 ± 0.51 MPa) was obtained for HA-CSM (5 wt% of CS) formulated at an S/L of 1. The dissolution tests of the HA-CS composites confirmed their cohesion and mechanical stability in an aqueous solution. Both polymer and apatite are assumed to work together, giving the synergism needed to make effective cylindrical composites, and could serve as a promising candidate for bone repair in the orthopedic field.

scholarly journals Bioresorbable Magnesium-Based Alloys as Novel Biomaterials in Oral Bone Regeneration: General Review and Clinical Perspectives

2021 ◽  
Vol 10 (9) ◽  
pp. 1842
Author(s):  
Valentin Herber ◽  
Begüm Okutan ◽  
Georgios Antonoglou ◽  
Nicole G. Sommer ◽  
Michael Payer
Keyword(s):  
Additive Manufacturing ◽  
Bone Regeneration ◽  
Modulus Of Elasticity ◽  
Bone Repair ◽  
Clinical Results ◽  
Porous Scaffolds ◽  
General Review ◽  
Synthetic Materials ◽  
Bone Preservation

Bone preservation and primary regeneration is a daily challenge in the field of dental medicine. In recent years, bioresorbable metals based on magnesium (Mg) have been widely investigated due to their bone-like modulus of elasticity, their high biocompatibility, antimicrobial, and osteoconductive properties. Synthetic Mg-based biomaterials are promising candidates for bone regeneration in comparison with other currently available pure synthetic materials. Different alloys based on Mg were developed to fit clinical requirements. In parallel, advances in additive manufacturing offer the possibility to fabricate experimentally bioresorbable metallic porous scaffolds. This review describes the promising clinical results of resorbable Mg-based biomaterials for bone repair in osteosynthetic application and discusses the perspectives of use in oral bone regeneration.

scholarly journals Regeneration of critical-sized defects, in a goat model, using a dextrin-based hydrogel associated with granular synthetic bone substitute

2020 ◽  
Author(s):  
Isabel Pereira ◽  
José Eduardo Pereira ◽  
Luís Maltez ◽  
Alexandra Rodrigues ◽  
Catarina Rodrigues ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Bone Substitute ◽  
Bone Substitutes ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Micro Computed Tomography ◽  
Synthetic Bone Substitute ◽  
In Situ Forming ◽  
Bioactive Agents ◽  
In Situ Forming Hydrogels

Abstract The development of injectable bone substitutes (IBS) have obtained great importance in the bone regeneration field, as a strategy to reach hardly accessible defects using minimally invasive techniques and able to fit to irregular topographies. In this scenario, the association of injectable hydrogels and bone graft granules is emerging as a well-established trend. Particularly, in situ forming hydrogels have arisen as a new IBS generation. An in situ forming and injectable dextrin-based hydrogel (HG) was developed, aiming to act as a carrier of granular bone substitutes and bioactive agents. In this work, the HG was associated to a granular bone substitute (Bonelike®) and implanted in goat critical-sized calvarial defects (14 mm) for 3, 6 and 12 weeks. The results showed that HG improved the handling properties of the Bonelike® granules and did not affect its osteoconductive features, neither impairing the bone regeneration process. Human multipotent mesenchymal stromal cells from the umbilical cord, extracellular matrix hydrolysates and the pro-angiogenic peptide LLKKK18 were also combined with the IBS. These bioactive agents did not enhance the new bone formation significantly under the conditions tested, according to micro-computed tomography and histological analysis.

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