scholarly journals Newly Designed Human-Like Collagen to Maximize Sensitive Release of BMP-2 for Remarkable Repairing of Bone Defects

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 450 ◽  
Author(s):  
Chen ◽  
Zhang ◽  
Ma ◽  
Duan ◽  
Hui ◽  
...  
Keyword(s):  
Sustained Release ◽  
Mechanical Strength ◽  
Bone Repair ◽  
Low Dose ◽  
Collagen Matrix ◽  
Bone Morphogenetic Protein 2 ◽  
Release Time ◽  
Hydrogel Matrix ◽  
Defect Repair

Designing the “ideal” hydrogel/matrix which can load bone morphogenetic protein-2 (BMP-2) in a low dose and with a sustained release is the key for its successful therapeutic application to enhance osteogenesis. The current use of natural collagen sponges as hydrogel/matrix is limited due to the collagen matrix showing weak mechanical strength and unmanageable biodegradability. Furthermore, the efficiency and safe dose usage of the BMP-2 has never been seriously considered other than purely chasing the lowest dose usage and extended-release time. In this paper, we customized a novel enzymatically cross-linked recombinant human-like collagen (HLC) sponge with low immunogenicity, little risk from hidden viruses, and easy production. We obtained a unique vertical pore structure and the porosity of the HLC, which are beneficial for Mesenchymal stem cells (MSCs) migration into the HLC sponge and angiopoiesis. This HLC sponge loading with low dose BMP-2 (1 µg) possessed high mechanical strength along with a burst and a sustained release profile. These merits overcome previous limitations of HLC in bone repair and are safer and more sensitive than commercial collagens. For the first time, we identified that a 5 µg dose of BMP-2 can bring about the side effect of bone overgrowth through this sensitive delivery system. Osteoinduction of the HLC-BMP sponges was proved by an in vivo mouse ectopic bone model and a rat cranial defect repair model. The method and the HLC-BMP sponge have the potential to release other growth factors and aid other tissue regeneration. Additionally, the ability to mass-produce HLC in our study overcomes the current supply shortage, which limits bone repair in the clinic.

scholarly journals A Comparative Genomic and Transcriptional Survey Providing Novel Insights into Bone Morphogenetic Protein 2 (bmp2) in Fishes

2019 ◽  
Vol 20 (24) ◽  
pp. 6137 ◽  
Author(s):  
Guang Yang ◽  
Zhendong Qin ◽  
Hongyan Kou ◽  
Rishen Liang ◽  
Lijuan Zhao ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Bone Repair ◽  
Fish Bone ◽  
Transcriptomic Analysis ◽  
Bone Morphogenetic Protein 2 ◽  
Comparative Genomic ◽  
Sequence Alignments ◽  
Cell Proliferation And Differentiation ◽  
Morphogenetic Protein

Intermuscular bones (IBs) are only found in the muscles of fish. Bone morphogenetic protein 2 (bmp2) is considered to be the most active single osteogenesis factor. It promotes cell proliferation and differentiation during bone repair, as well as inducing the formation of bones and cartilages in vivo. However, detailed investigations of this family in fish are incredibly limited. Here, we have used a variety of published and unpublished bmp2 sequences for teleosts and cartilage fish in order to explore and expand our understanding of bmp2 genes in fish. Our results confirmed that teleost genomes contain two or more bmp2 genes, and the diversity of bmp2 genes in vertebrates appears to be as a result of a combination of whole genome duplication (WGD) and gene loss. Differences were also observed in tissue distribution and relative transcription abundance of the bmp2s through a transcriptomic analysis. Our data also indicated that bmp2b may play an important role in the formation of IBs in teleosts. In addition, protein sequence alignments and 3D structural predictions of bmp2a and bmp2b supported their similar roles in fishes. To summarize, our existing work provided novel insights into the bmp2 family genes in fishes through a mixture of comparative genomic and transcriptomic analysis.

scholarly journals Enhanced BMP-2-Mediated Bone Repair Using an Anisotropic Silk Fibroin Scaffold Coated with Bone-like Apatite

2021 ◽  
Vol 23 (1) ◽  
pp. 283
Author(s):  
Christian Deininger ◽  
Andrea Wagner ◽  
Patrick Heimel ◽  
Elias Salzer ◽  
Xavier Monforte Vila ◽  
...  
Keyword(s):  
Bone Repair ◽  
Bone Morphogenetic Protein 2 ◽  
Great Promise ◽  
Calcium Phosphate Coating ◽  
Graft Material ◽  
Morphogenetic Protein ◽  
Silk Scaffolds ◽  
Cost Efficient

The repair of large bone defects remains challenging and often requires graft material due to limited availability of autologous bone. In clinical settings, collagen sponges loaded with excessive amounts of bone morphogenetic protein 2 (rhBMP-2) are occasionally used for the treatment of bone non-unions, increasing the risk of adverse events. Therefore, strategies to reduce rhBMP-2 dosage are desirable. Silk scaffolds show great promise due to their favorable biocompatibility and their utility for various biofabrication methods. For this study, we generated silk scaffolds with axially aligned pores, which were subsequently treated with 10× simulated body fluid (SBF) to generate an apatitic calcium phosphate coating. Using a rat femoral critical sized defect model (CSD) we evaluated if the resulting scaffold allows the reduction of BMP-2 dosage to promote efficient bone repair by providing appropriate guidance cues. Highly porous, anisotropic silk scaffolds were produced, demonstrating good cytocompatibility in vitro and treatment with 10× SBF resulted in efficient surface coating. In vivo, the coated silk scaffolds loaded with a low dose of rhBMP-2 demonstrated significantly improved bone regeneration when compared to the unmineralized scaffold. Overall, our findings show that this simple and cost-efficient technique yields scaffolds that enhance rhBMP-2 mediated bone healing.

scholarly journals Biocompatible PLGA-Mesoporous Silicon Microspheres for the Controlled Release of BMP-2 for Bone Augmentation

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 118 ◽  
Author(s):  
Silvia Minardi ◽  
Joseph S. Fernandez-Moure ◽  
Dongmei Fan ◽  
Matthew B. Murphy ◽  
Iman K. Yazdi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Sustained Release ◽  
Release Kinetics ◽  
In Vitro Release ◽  
Bone Morphogenetic Protein 2 ◽  
Osteogenic Potential ◽  
Bone Augmentation

Bone morphogenetic protein-2 (BMP-2) has been demonstrated to be one of the most vital osteogenic factors for bone augmentation. However, its uncontrolled administration has been associated with catastrophic side effects, which compromised its clinical use. To overcome these limitations, we aimed at developing a safer controlled and sustained release of BMP-2, utilizing poly(lactic-co-glycolic acid)-multistage vector composite microspheres (PLGA-MSV). The loading and release of BMP-2 from PLGA-MSV and its osteogenic potential in vitro and in vivo was evaluated. BMP-2 in vitro release kinetics was assessed by ELISA assay. It was found that PLGA-MSV achieved a longer and sustained release of BMP-2. Cell cytotoxicity and differentiation were evaluated in vitro by MTT and alkaline phosphatase (ALP) activity assays, respectively, with rat mesenchymal stem cells. The MTT results confirmed that PLGA-MSVs were not toxic to cells. ALP test demonstrated that the bioactivity of BMP-2 released from the PLGA-MSV was preserved, as it allowed for the osteogenic differentiation of rat mesenchymal stem cells, in vitro. The biocompatible, biodegradable, and osteogenic PLGA-MSVs system could be an ideal candidate for the safe use of BMP-2 in orthopedic tissue engineering applications.

Enhanced bioactivity of bone morphogenetic protein-2 with low dose of 2-N, 6-O-sulfated chitosan in vitro and in vivo

Biomaterials ◽  
2009 ◽  
Vol 30 (9) ◽  
pp. 1715-1724 ◽  
Author(s):  
Huanjun Zhou ◽  
Jiangchao Qian ◽  
Jing Wang ◽  
Wantong Yao ◽  
Changsheng Liu ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Low Dose ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein

scholarly journals Research Advances in Tissue Engineering Materials for Sustained Release of Growth Factors

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Hai-yang Zhao ◽  
Jiang Wu ◽  
Jing-jing Zhu ◽  
Ze-cong Xiao ◽  
Chao-chao He ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Growth Factors ◽  
Sustained Release ◽  
Enzymatic Degradation ◽  
Bone Repair ◽  
Sustained Delivery ◽  
System Disease ◽  
Free Growth ◽  
Intense Research

Growth factors are a class of cytokines that stimulate cell growth and are widely used in clinical practice, such as wound healing, revascularization, bone repair, and nervous system disease. However, free growth factors have a short half-life and are instablein vivo. Therefore, the search of excellent carriers to enhance sustained release of growth factorsin vivohas become an area of intense research interest. The development of controlled-release systems that protect the recombinant growth factors from enzymatic degradation and provide sustained delivery at the injury site during healing should enhance the growth factor’s application in tissue regeneration. Thus, this study reviews current research on commonly used carriers for sustained release of growth factors and their sustained release effects for preservation of their bioactivity and their accomplishment in tissue engineering approaches.

Superparamagnetic Core–Shell Electrospun Scaffolds with Sustained Release of IONPs Facilitating in vitro and in vivo Bone Regeneration

2021 ◽  
Author(s):  
Shuying Hu ◽  
Hanbang Chen ◽  
Fang Zhou ◽  
Jun Liu ◽  
Yun Zhu Qian ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Sustained Release ◽  
Mechanical Strength ◽  
Bone Tissue Engineering ◽  
Bone Regeneration ◽  
Core Shell ◽  
Electrospun Scaffolds ◽  
Dental Implantation

Bone tissue engineering (BTE) is a promising approach to recover insufficient bone in dental implantation. However, the clinical application of BTE scaffolds is limited by their low mechanical strength and...

scholarly journals Sustained Release of Bone Morphogenetic Protein-2 through Alginate Microbeads Enhances Bone Regeneration in Rabbit Tibial Metaphyseal Defect Model

Materials ◽  
2021 ◽  
Vol 14 (10) ◽  
pp. 2600
Author(s):  
Junhyung Kim ◽  
Seoyun Lee ◽  
Yonghyun Choi ◽  
Jonghoon Choi ◽  
Byung-Jae Kang
Keyword(s):  
Sustained Release ◽  
Bone Regeneration ◽  
Bone Morphogenetic Protein ◽  
Bone Volume ◽  
Bone Morphogenetic Protein 2 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Micro Computed Tomography ◽  
Combined Application ◽  
Morphogenetic Protein

Bone morphogenetic protein-2 (BMP-2) is widely used to enhance bone regeneration. However, because of its short half-life and rapid disappearance, large amounts of BMP-2 are needed, leading to unintended side effects. In this study, BMP-2-encapsulated alginate microbeads (AM) were used to enhance bone regeneration. Enzyme-linked immunosorbent assay confirmed the sustained release of BMP-2 from AM. Vascular endothelial growth factor (VEGF)-adsorbing aptamer-conjugated hydroxyapatite (Apt-HA) was used for osteoconduction and dual delivery of VEGF and BMP-2. For in vivo bone regeneration evaluation, the grafts (1) Apt-HA + phosphate-buffered saline (PBS), (2) Apt-HA + AM without BMP-2, (3) Apt-HA + BMP-2, and (4) Apt-HA + AM encapsulated with BMP-2 were implanted into rabbit tibial metaphyseal defects. After four weeks, micro-computed tomography (CT), histological, and histomorphometric analyses were performed to evaluate bone regeneration. The Apt-HA + AM with BMP-2 group revealed a significantly higher new bone volume and bone volume/total volume (BV/TV) in both cortical and trabecular bone than the others. Furthermore, as evaluated by histomorphometric analysis, BMP-2 AM exhibited a significantly higher bone formation area than the others, indicating that AM could be used to efficiently deliver BMP-2 through sustained release. Moreover, the combined application of BMP-2-encapsulated Apt-HA + AM may effectively promote bone regeneration.

Low dose BMP-2 treatment for bone repair using a PEGylated fibrinogen hydrogel matrix

Biomaterials ◽  
2013 ◽  
Vol 34 (12) ◽  
pp. 2902-2910 ◽  
Author(s):  
Dror Ben-David ◽  
Samer Srouji ◽  
Keren Shapira-Schweitzer ◽  
Olga Kossover ◽  
Eran Ivanir ◽  
...  
Keyword(s):  
Bone Repair ◽  
Low Dose ◽  
Hydrogel Matrix

scholarly journals In Vivo Biological Behavior of Polymer Scaffolds of Natural Origin in the Bone Repair Process

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1598
Author(s):  
Fernando Bento Cunha ◽  
Karina Torres Pomini ◽  
Ana Maria de Guzzi Plepis ◽  
Virgínia da Conceição Amaro Martins ◽  
Eduardo Gomes Machado ◽  
...  
Keyword(s):  
Bone Defect ◽  
Bone Repair ◽  
Bone Growth ◽  
Critical Size ◽  
Blood Clot ◽  
Collagen Matrix ◽  
Repair Process ◽  
Biological Behavior ◽  
Control Group

Autologous bone grafts, used mainly in extensive bone loss, are considered the gold standard treatment in regenerative medicine, but still have limitations mainly in relation to the amount of bone available, donor area, morbidity and creation of additional surgical area. This fact encourages tissue engineering in relation to the need to develop new biomaterials, from sources other than the individual himself. Therefore, the present study aimed to investigate the effects of an elastin and collagen matrix on the bone repair process in critical size defects in rat calvaria. The animals (Wistar rats, n = 30) were submitted to a surgical procedure to create the bone defect and were divided into three groups: Control Group (CG, n = 10), defects filled with blood clot; E24/37 Group (E24/37, n = 10), defects filled with bovine elastin matrix hydrolyzed for 24 h at 37 °C and C24/25 Group (C24/25, n = 10), defects filled with porcine collagen matrix hydrolyzed for 24 h at 25 °C. Macroscopic and radiographic analyses demonstrated the absence of inflammatory signs and infection. Microtomographical 2D and 3D images showed centripetal bone growth and restricted margins of the bone defect. Histologically, the images confirmed the pattern of bone deposition at the margins of the remaining bone and without complete closure by bone tissue. In the morphometric analysis, the groups E24/37 and C24/25 (13.68 ± 1.44; 53.20 ± 4.47, respectively) showed statistically significant differences in relation to the CG (5.86 ± 2.87). It was concluded that the matrices used as scaffolds are biocompatible and increase the formation of new bone in a critical size defect, with greater formation in the polymer derived from the intestinal serous layer of porcine origin (C24/25).

scholarly journals Hesperidin Promotes Osteogenesis and Modulates Collagen Matrix Organization and Mineralization In Vitro and In Vivo

2021 ◽  
Vol 22 (6) ◽  
pp. 3223
Author(s):  
Patricia A. Miguez ◽  
Stephen A. Tuin ◽  
Adam G. Robinson ◽  
Joyce Belcher ◽  
Prapaporn Jongwattanapisan ◽  
...  
Keyword(s):  
Cell Function ◽  
Organic Matrix ◽  
Collagen Matrix ◽  
Bone Morphogenetic Protein 2 ◽  
Tissue Formation ◽  
Osteoblast Cell ◽  
Mineralized Tissue ◽  
Matrix Organization

This study evaluated the direct effect of a phytochemical, hesperidin, on pre-osteoblast cell function as well as osteogenesis and collagen matrix quality, as there is little known about hesperidin’s influence in mineralized tissue formation and regeneration. Hesperidin was added to a culture of MC3T3-E1 cells at various concentrations. Cell proliferation, viability, osteogenic gene expression and deposited collagen matrix analyses were performed. Treatment with hesperidin showed significant upregulation of osteogenic markers, particularly with lower doses. Mature and compact collagen fibrils in hesperidin-treated cultures were observed by picrosirius red staining (PSR), although a thinner matrix layer was present for the higher dose of hesperidin compared to osteogenic media alone. Fourier-transform infrared spectroscopy indicated a better mineral-to-matrix ratio and matrix distribution in cultures exposed to hesperidin and confirmed less collagen deposited with the 100-µM dose of hesperidin. In vivo, hesperidin combined with a suboptimal dose of bone morphogenetic protein 2 (BMP2) (dose unable to promote healing of a rat mandible critical-sized bone defect) in a collagenous scaffold promoted a well-controlled (not ectopic) pattern of bone formation as compared to a large dose of BMP2 (previously defined as optimal in healing the critical-sized defect, although of ectopic nature). PSR staining of newly formed bone demonstrated that hesperidin can promote maturation of bone organic matrix. Our findings show, for the first time, that hesperidin has a modulatory role in mineralized tissue formation via not only osteoblast cell differentiation but also matrix organization and matrix-to-mineral ratio and could be a potential adjunct in regenerative bone therapies.

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