scholarly journals Nano-Hydroxyapatite as A Delivery System for Promoting Bone Regeneration In Vivo: A Systematic Review

Nanomaterials ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 2569
Author(s):  
Anis Syauqina Mohd Zaffarin ◽  
Shiow-Fern Ng ◽  
Min Hwei Ng ◽  
Haniza Hassan ◽  
Ekram Alias

Nano-hydroxyapatite (nHA) has been widely used as an orthopedic biomaterial and vehicle for drug delivery owing to its chemical and structural similarity to bone minerals. Several studies have demonstrated that nHA based biomaterials have a potential effect for bone regeneration with very minimal to no toxicity or inflammatory response. This systematic review aims to provide an appraisal of the effectiveness of nHA as a delivery system for bone regeneration and whether the conjugation of proteins, antibiotics, or other bioactive molecules to the nHA further enhances osteogenesis in vivo. Out of 282 articles obtained from the literature search, only 14 articles met the inclusion criteria for this review. These studies showed that nHA was able to induce bone regeneration in various animal models with large or critical-sized bone defects, open fracture, or methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis. The conjugations of drugs or bioactive molecules such as bone-morphogenetic protein-2 (BMP-2), vancomycin, calcitriol, dexamethasone, and cisplatin were able to enhance the osteogenic property of nHA. Thus, nHA is a promising delivery system for a variety of compounds in promoting bone regeneration in vivo.

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 979
Author(s):  
Patricia Garcia-Garcia ◽  
Ricardo Reyes ◽  
José Antonio Rodriguez ◽  
Tomas Martín ◽  
Carmen Evora ◽  
...  

Biomaterials-mediated bone formation in osteoporosis (OP) is challenging as it requires tissue growth promotion and adequate mineralization. Based on our previous findings, the development of scaffolds combining bone morphogenetic protein 2 (BMP-2) and matrix metalloproteinase 10 (MMP-10) shows promise for OP management. To test our hypothesis, scaffolds containing BMP-2 + MMP-10 at variable ratios or BMP-2 + Alendronate (ALD) were prepared. Systems were characterized and tested in vitro on healthy and OP mesenchymal stem cells and in vivo bone formation was studied on healthy and OP animals. Therapeutic molecules were efficiently encapsulated into PLGA microspheres and embedded into chitosan foams. The use of PLGA (poly(lactic-co-glycolic acid)) microspheres as therapeutic molecule reservoirs allowed them to achieve an in vitro and in vivo controlled release. A beneficial effect on the alkaline phosphatase activity of non-OP cells was observed for both combinations when compared with BMP-2 alone. This effect was not detected on OP cells where all treatments promoted a similar increase in ALP activity compared with control. The in vivo results indicated a positive effect of the BMP-2 + MMP-10 combination at both of the doses tested on tissue repair for OP mice while it had the opposite effect on non-OP animals. This fact can be explained by the scaffold’s slow-release rate and degradation that could be beneficial for delayed bone regeneration conditions but had the reverse effect on healthy animals. Therefore, the development of adequate scaffolds for bone regeneration requires consideration of the tissue catabolic/anabolic balance to obtain biomaterials with degradation/release behaviors suited for the existing tissue status.


2021 ◽  
Vol 22 ◽  
pp. 100906
Author(s):  
Zhichao Hu ◽  
Qian Tang ◽  
Deyi Yan ◽  
Gang Zheng ◽  
Mingbao Gu ◽  
...  

2019 ◽  
Vol 24 (2) ◽  
pp. 569-584 ◽  
Author(s):  
Franz-Josef Strauss ◽  
Jila Nasirzade ◽  
Zahra Kargarpoor ◽  
Alexandra Stähli ◽  
Reinhard Gruber

Abstract Objective To systematically assess the effects of platelet-rich fibrin (PRF) on in vitro cellular behavior. Methods A systematic electronic search using MEDLINE database was performed. In vitro studies using PRF were considered and articles published up to June 31, 2018 were screened. Eligible studies were selected based on the use of human PRF. Results In total, 1746 titles were identified with the search terms, from these 37 met the inclusion criteria and were chosen for data extraction. In addition, 16 new studies, mainly published in 2019, were also included in the analysis resulting in 53 studies. No meta-analysis could be performed due to the heterogeneity of study designs. Included studies show that PRF enhances proliferation, migration, adhesion, and osteogenic differentiation on a variety of cell types along with cell signaling activation. Furthermore, PRF reduces inflammation, suppresses osteoclastogenesis, and increases the expression of various growth factors in mesenchymal cells. Summary and conclusions Despite some notable differences of the studies, the overall findings suggest a positive effect of PRF on cell proliferation, migration, adhesion, differentiation, and inflammation pointing towards a therapeutic potential in regenerative dentistry. Clinical relevance PRF serves as a reservoir of bioactive molecules to support wound healing and bone regeneration. Although the cellular mechanisms by which PRF supports the clinical outcomes remain unclear, in vitro research provides possible explanations. This systematic review aims to provide an update of the existing research on how PRF affects basic physiological processes in vitro. The overall findings suggest that PRF induces cell proliferation, migration, adhesion, and differentiation along with possessing anti-inflammatory properties further supporting its therapeutic potential in wound healing and bone regeneration.


Symmetry ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 229 ◽  
Author(s):  
Janis Zarins ◽  
Mara Pilmane ◽  
Elga Sidhoma ◽  
Ilze Salma ◽  
Janis Locs

Background: Strontium (Sr) enriched biomaterials have been used to improve bone regeneration in vivo. However, most studies provide only two experimental groups. The aim of our study was to compare eleven different bone sample groups from osteoporotic and healthy rabbits’ femoral neck, as it is the most frequent osteoporotic fracture in humans. Methods: Osteoporotic bone defects were filled with hydroxyapatite 30% (HA) and tricalcium phosphate 70% (TCP), 5% Sr-enriched HA30/TCP70, HA70/TCP30, or Sr-HA70/TCP30 granules and were compared with intact leg, sham surgery and healthy non-operated bone. Expression of osteoprotegerin (OPG), nuclear factor kappa beta 105 (NFkB-105), osteocalcin (OC), bone morphogenetic protein 2/4 (BMP-2/4), collagen I (Col-1α), matrix metalloproteinase 2 (MMP-2), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), interleukin 1 (IL-1) and interleukin 10 (IL-10) was analyzed by histomorphometry and immunohistochemistry. Results: Our study showed that Sr-HA70/TCP30 induced higher expression of all above-mentioned factors compared to intact leg and even higher expression of OC, MMP-2 and NFkB-105 compared to Sr-HA30/TCP70. HA70/TCP30 induced higher level of NFkB-105 and IL-1 compared to HA30/TCP70. Conclusion: Sr-enriched biomaterials improved bone regeneration at molecular level in severe osteoporosis and induced activity of the factors was higher than after pure ceramic, sham or even healthy rabbits.


2017 ◽  
Vol 4 (S) ◽  
pp. 139
Author(s):  
Min Ji Kim ◽  
Jin Hyun Park ◽  
Ho Yong Kim ◽  
June Ho Byun ◽  
Jin Ho Lee ◽  
...  

Sound healing of large bone defects is critical challenges in most of clinical fields. In general healing process of bone regeneration, the rapid infiltration of connective tissue, whereas relatively slow bone regeneration in bone defect leads to the incomplete bone formation. To solve this drawback, guide bone regeneration (GBR) membrane which could prevent rapid infiltration of connective tissue into bone defect, thus GBR membrane is feasible for compact bone regeneration in clinical fields. In recent, the most researchers believed that bioactive molecules-grafted GBR membranes may enhance the bone regeneration. To allow graft of bioactive molecules from porous membrane, chemically modified scaffolds are commonly used. This modification leads to sufficient interaction with active sites of bioactive molecules to stable the immobilization of bioactive molecules in the body. However it is hard to apply to clinical applications because of the toxicity of chemical residue used for the modification. In this study, we developed a GBR membrane with leaf-stacked structure which can allow sustained release of bone morphogenetic protein-2 (BMP-2) without any additional modification. The morphology, mechanical property, BMP-2 release profile, osteogenic differentiation of human periosteum-derived cells, and new bone formation efficiency of the BMP-2-loaded GBR membrane compared with commercial product were investigated.


2021 ◽  
Author(s):  
Casey E. Vantucci ◽  
Laxminarayanan Krishan ◽  
Albert Cheng ◽  
Ayanna Prather ◽  
Krishnendu Roy ◽  
...  

Bone nonunions remain compelling orthopedic challenges. Bone morphogenetic protein-2 (BMP-2) delivered in a heparin microparticle (HMP) delivery system improved local bone regeneration compared to BMP-2 delivered in the clinical standard collagen sponge.


Materials ◽  
2021 ◽  
Vol 14 (10) ◽  
pp. 2600
Author(s):  
Junhyung Kim ◽  
Seoyun Lee ◽  
Yonghyun Choi ◽  
Jonghoon Choi ◽  
Byung-Jae Kang

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.


2021 ◽  
Vol 9 (F) ◽  
pp. 470-473
Author(s):  
Hanif Andhika Wardhana ◽  
Mujaddid Idulhaq ◽  
Rhyan Darma Saputra ◽  
Rieva Ermawan ◽  
Musa Fasa Roshada

Background : The use of Bone Graft in the management of Bone Defect is a challenge in the world of orthopedics. Recently, eggshell containing hydroxyapatite has become a new hope in the use of an economical and efficient bone graft in the treatment of bone defects. The aim of this systematic review was to explore the available literature on the clinical performance of eggshells as bone grafts in guided bone regeneration. Method : Two databases (PubMed and Cochrane) were searched from January 2010 to September 2020. Clinical trials using eggshells as bone grafts were included in the review. Animal and in vivo studies were excluded from the review. Results : A total of 202 studies were taken, then screened and 15 studies finally included. Clinical and radiological evaluations show complete recovery after the procedure. Comparison with synthetic hydroxyapatite shows similar healing characteristics. Conclusion : Eggshell compared to bovine showed no difference in bone healing. Within the limitations of the included studies, eggshells can be used safely and efficiently in integrated bone regeneration procedures. Keywords: Bone tissue regeneration; eggshell; bovine; bone defect; bone graft  


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