scholarly journals Biomimetic Synthesis of Nanocrystalline Hydroxyapatite Composites: Therapeutic Potential and Effects on Bone Regeneration

2019 ◽  
Vol 20 (23) ◽  
pp. 6002 ◽  
Author(s):  
Chih-Hsiang Fang ◽  
Yi-Wen Lin ◽  
Feng-Huei Lin ◽  
Jui-Sheng Sun ◽  
Yuan-Hung Chao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Bone Regeneration ◽  
Stromal Cell ◽  
Alveolar Bone ◽  
Therapeutic Potential ◽  
Bone Defects ◽  
Stromal Cell Derived Factor ◽  
Biomimetic Hydroxyapatite

The development of a novel alloplastic graft with both osteoinductive and osteoconductive properties is still necessary. In this study, we tried to synthesize a biomimetic hydroxyapatite microspheres (gelatin/nano-hydroxyapatite microsphere embedded with stromal cell-derived factor-1: GHM-S) from nanocrystalline hydroxyapatites and to investigate their therapeutic potential and effects on bone regeneration. In this study, hydroxyapatite was synthesized by co-precipitation of calcium hydroxide and orthophosphoric acid to gelatin solution. The microbial transglutaminase was used as the agent to crosslink the microspheres. The morphology, characterization, and thermal gravimetric analysis of microspheres were performed. SDF-1 release profile and in vitro biocompatibility and relative osteogenic gene expression were analyzed, followed by in vivo micro-computed tomography study and histological analysis. The synthesized hydroxyapatite was found to be similar to hydroxyapatite of natural bone tissue. The stromal cell-derived factor-1 was embedded into gelatin/hydroxyapatite microsphere to form the biomimetic hydroxyapatite microsphere. The stromal cell-derived factor-1 protein could be released in a controlled manner from the biomimetic hydroxyapatite microsphere and form a concentration gradient in the culture environment to attract the migration of stem cells. Gene expression and protein expression indicated that stem cells could differentiate or develop into pre-osteoblasts. The effect of bone formation by the biomimetic hydroxyapatite microsphere was assessed by an in vivo rats’ alveolar bone defects model and confirmed by micro-CT imaging and histological examination. Our findings demonstrated that the biomimetic hydroxyapatite microsphere can enhance the alveolar bone regeneration. This design has potential be applied to other bone defects.

scholarly journals Potential Implantable Nanofibrous Biomaterials Combined with Stem Cells for Subchondral Bone Regeneration

Materials ◽  
2020 ◽  
Vol 13 (14) ◽  
pp. 3087
Author(s):  
Rana Smaida ◽  
Luc Pijnenburg ◽  
Silvia Irusta ◽  
Erico Himawan ◽  
Gracia Mendoza ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Regeneration ◽  
Subchondral Bone ◽  
Therapeutic Potential ◽  
Sodium Hyaluronate ◽  
Vinyl Pyrrolidone ◽  
Regenerative Ability ◽  
Poly Vinyl Pyrrolidone

The treatment of osteochondral defects remains a challenge. Four scaffolds were produced using Food and Drug Administration (FDA)-approved polymers to investigate their therapeutic potential for the regeneration of the osteochondral unit. Polycaprolactone (PCL) and poly(vinyl-pyrrolidone) (PVP) scaffolds were made by electrohydrodynamic techniques. Hydroxyapatite (HAp) and/or sodium hyaluronate (HA) can be then loaded to PCL nanofibers and/or PVP particles. The purpose of adding hydroxyapatite and sodium hyaluronate into PCL/PVP scaffolds is to increase the regenerative ability for subchondral bone and joint cartilage, respectively. Human bone marrow-derived mesenchymal stem cells (hBM-MSCs) were seeded on these biomaterials. The biocompatibility of these biomaterials in vitro and in vivo, as well as their potential to support MSC differentiation under specific chondrogenic or osteogenic conditions, were evaluated. We show here that hBM-MSCs could proliferate and differentiate both in vitro and in vivo on these biomaterials. In addition, the PCL-HAp could effectively increase the mineralization and induce the differentiation of MSCs into osteoblasts in an osteogenic condition. These results indicate that PCL-HAp biomaterials combined with MSCs could be a beneficial candidate for subchondral bone regeneration.

The potential of stromal cell-derived factor-1 delivery using a collagen membrane for bone regeneration

2017 ◽  
Vol 31 (7) ◽  
pp. 1049-1061 ◽  
Author(s):  
Tadahiro Takayama ◽  
Jisen Dai ◽  
Keita Tachi ◽  
Ryutaro Shohara ◽  
Hironori Kasai ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Stromal Cell ◽  
In Vitro Studies ◽  
New Bone Formation ◽  
Stromal Cell Derived Factor

Stromal cell-derived factor-1 (SDF-1) is a cytokine that is important in stem and progenitor cell recruitment in tissue repair after injury. Regenerative procedures using collagen membranes (CMs) are presently well established in periodontal and implant dentistry. The objective of this study is to test the subsequent effects of the released SDF-1 from a CM on bone regeneration compared to platelet-derived growth factor (PDGF) in vitro and in vivo. For in vitro studies, cell proliferation, alkaline phosphatase activity, and osteoblastic differentiation marker genes were assessed after MC3T3-E1 mouse preosteoblasts were cultured with CMs containing factors. In vivo effects were investigated by placement of CMs containing SDF-1 or PDGF using a rat mandibular bone defect model. At 4 weeks after the surgery, the new bone formation was measured using micro-computed tomography (µCT) and histological analysis. The results of in vitro studies revealed that CM delivery of SDF-1 significantly induced cell proliferation, ALP activity, and gene expression of all osteogenic markers compared to the CM alone or control, similar to PDGF. Quantitative and qualitative µCT analysis for volume of new bone formation and the percentage of new bone area showed that SDF-1-treated groups significantly increased and accelerated bone regeneration compared to control and CM alone. The enhancement of bone formation in SDF-1-treated animals was dose-dependent and with levels similar to those measured with PDGF. These results suggest that a CM with SDF-1 may be a great candidate for growth factor delivery that could be a substitute for PDGF in clinical procedures where bone regeneration is necessary.

scholarly journals The Development of Gelatin/Hyaluronate Copolymer Mixed with Calcium Sulfate, Hydroxyapatite, and Stromal-Cell-Derived Factor-1 for Bone Regeneration Enhancement

Polymers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1454 ◽  
Author(s):  
Yun-Liang Chang ◽  
Chia-Ying Hsieh ◽  
Chao-Yuan Yeh ◽  
Feng-Huei Lin
Keyword(s):  
Bone Regeneration ◽  
Bone Defect ◽  
Calcium Sulfate ◽  
Stromal Cell ◽  
Femoral Condyle ◽  
Bone Defects ◽  
Blood Analysis ◽  
Control Group ◽  
Defect Model ◽  
Stromal Cell Derived Factor

In clinical practice, bone defects still remain a challenge. In recent years, apart from the osteoconductivity that most bone void fillers already provide, osteoinductivity has also been emphasized to promote bone healing. Stromal-cell-derived factor-1 (SDF-1) has been shown to have the ability to recruit mesenchymal stem cells (MSCs), which play an important role in the bone regeneration process. In this study, we developed a gelatin–hyaluronate (Gel-HA) copolymer mixed with calcium sulfate (CS), hydroxyapatite (HAP), and SDF-1 in order to enhance bone regeneration in a bone defect model. The composites were tested in vitro for biocompatibility and their ability to recruit MSCs after material characterization. For the in vivo test, a rat femoral condyle bone defect model was used. Micro computed tomography (Micro-CT), two-photon excitation microscopy, and histology analysis were performed to assess bone regeneration. As expected, enhanced bone regeneration was well observed in the group filled with Gel-HA/CS/HAP/SDF-1 composites compared with the control group in our animal model. Furthermore, detailed blood analysis of rats showed no obvious systemic toxicity or side effects after material implantation. In conclusion, the Gel-HA/CS/HAP/SDF-1 composite may be a safe and applicable material to enhance bone regeneration in bone defects.

scholarly journals Fabrication of Stromal Cell-Derived Factor-1 Contained in Gelatin/Hyaluronate Copo006Cymer Mixed with Hydroxyapatite for Use in Traumatic Bone Defects

Micromachines ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 822
Author(s):  
Yun-Liang Chang ◽  
Chia-Ying Hsieh ◽  
Chao-Yuan Yeh ◽  
Chih-Hao Chang ◽  
Feng-Huei Lin
Keyword(s):  
Bone Regeneration ◽  
Bone Defect ◽  
Stromal Cell ◽  
Second Harmonic ◽  
Bone Defects ◽  
In Vivo Studies ◽  
Control Group ◽  
Defect Model ◽  
Stromal Cell Derived Factor ◽  
Bone Void

Bone defects of orthopedic trauma remain a challenge in clinical practice. Regarding bone void fillers, besides the well-known osteoconductivity of most bone substitutes, osteoinductivity has also been gaining attention in recent years. It is known that stromal cell-derived factor-1 (SDF-1) can recruit mesenchymal stem cells (MSCs) in certain circumstances, which may also play an important role in bone regeneration. In this study, we fabricated a gelatin/hyaluronate (Gel/HA) copolymer mixed with hydroxyapatite (HAP) and SDF-1 to try and enhance bone regeneration in a bone defect model. After material characterization, these Gel/HA–HAP and Gel/HA–HAP–SDF-1 composites were tested for their biocompatibility and ability to recruit MSCs in vitro. A femoral condyle bone defect model of rats was used for in vivo studies. For the assessment of bone healing, micro-CT analysis, second harmonic generation (SHG) imaging, and histology studies were performed. As a result, the Gel/HA–HAP composites showed no systemic toxicity to rats. Gel/HA–HAP composite groups both showed better bone generation compared with the control group in an animal study, and the composite with the SDF-1 group even showed a trend of faster bone growth compared with the composite without SDF-1 group. In conclusion, in the management of traumatic bone defects, Gel/HA–HAP–SDF-1 composites can be a feasible material for use as bone void fillers.

Strontium folate loaded biohybrid scaffolds seeded with dental pulp stem cells induce in vivo bone regeneration in critical sized defects

2016 ◽  
Vol 4 (11) ◽  
pp. 1596-1604 ◽  
Author(s):  
Marcela Martin-del-Campo ◽  
Raul Rosales-Ibañez ◽  
Keila Alvarado ◽  
Jose G. Sampedro ◽  
Christian A. Garcia-Sepulveda ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Regeneration ◽  
Dental Pulp ◽  
Bone Defects ◽  
Dental Pulp Stem Cells ◽  
Critical Bone Defects ◽  
Complete Regeneration

Strontium folate loaded biohybrid scaffolds enhance dental pulp stem cells replication and differentiation, promoting complete regeneration of critical bone defects.

scholarly journals In Vivo Investigation of Polymer-Ceramic PCL/HA and PCL/β-TCP 3D Composite Scaffolds and Electrical Stimulation for Bone Regeneration

Polymers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 65
Author(s):  
Júlia Venturini Helaehil ◽  
Carina Basqueira Lourenço ◽  
Boyang Huang ◽  
Luiza Venturini Helaehil ◽  
Isaque Xavier de Camargo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Electrical Stimulation ◽  
Bone Regeneration ◽  
Bone Defects ◽  
Composite Scaffolds ◽  
Electrical Therapy ◽  
Biological Recognition ◽  
3D Composite ◽  
Critical Bone Defects

Critical bone defects are a major clinical challenge in reconstructive bone surgery. Polycaprolactone (PCL) mixed with bioceramics, such as hydroxyapatite (HA) and tricalcium phosphate (TCP), create composite scaffolds with improved biological recognition and bioactivity. Electrical stimulation (ES) aims to compensate the compromised endogenous electrical signals and to stimulate cell proliferation and differentiation. We investigated the effects of composite scaffolds (PCL with HA; and PCL with β-TCP) and the use of ES on critical bone defects in Wistar rats using eight experimental groups: untreated, ES, PCL, PCL/ES, HA, HA/ES, TCP, and TCP/ES. The investigation was based on histomorphometry, immunohistochemistry, and gene expression analysis. The vascular area was greater in the HA/ES group on days 30 and 60. Tissue mineralization was greater in the HA, HA/ES, and TCP groups at day 30, and TCP/ES at day 60. Bmp-2 gene expression was higher in the HA, TCP, and TCP/ES groups at day 30, and in the TCP/ES and PCL/ES groups at day 60. Runx-2, Osterix, and Osteopontin gene expression were also higher in the TCP/ES group at day 60. These results suggest that scaffolds printed with PCL and TCP, when paired with electrical therapy application, improve bone regeneration.

scholarly journals Analysis of mineral apposition rates during alveolar bone regeneration over three weeks following transfer of BMP-2/7 gene via in vivo electroporation

2018 ◽  
Author(s):  
Mariko Kawai ◽  
Yohei Kataoka ◽  
Junya Sonobe ◽  
Hiromitsu Yamamoto ◽  
Hiroki Maruyama ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Transfer ◽  
Bone Regeneration ◽  
Expression Vector ◽  
Alveolar Bone ◽  
Plasmid Vector ◽  
Periodontal Tissue ◽  
In Vivo Electroporation ◽  
Regeneration Potential

Alveolar bone is not spontaneously regenerated following trauma or periodontitis. We previously proposed an animal model for new alveolar bone regeneration therapy based on the non-viral BMP-2/7 gene expression vector and in vivo electroporation, which induced the formation of new alveolar bone over the course of a week. Here, we analysed alveolar bone during a period of three weeks following gene transfer to periodontal tissue. Non-viral plasmid vector pCAGGS-BMP-2/7 or pCAGGS control was injected into palatal periodontal tissue of the first molar of the rat maxilla and immediately electroporated with 32 pulses of 50 V for 50 msec. Over the following three weeks, rats were double bone-stained by calcein and tetracycline every three days and mineral apposition rates (MAR) were measured. Double bone-staining revealed that MAR of alveolar bone was as similar level three days before BMP-2/7 gene transfer as three days after gene transfer. However, from 3 to 6 days, 6 to 9 days, 9 to 12 days, 12 to 15 days, 15 to 18 days, and 18 to 20 days after, MARs were significantly higher than prior to gene transfer. Our proposed gene therapy for alveolar bone regeneration combining non-viral BMP-2/7 gene expression vector and in vivo electroporation could increase alveolar bone regeneration potential in the targeted area for up to three weeks.

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