scholarly journals Localized delivery of β-NGF via injectable microrods accelerates endochondral fracture repair

2021 ◽  
Author(s):  
Kevin O. Rivera ◽  
Darnell L Cuylear ◽  
Victoria Duke ◽  
Kelsey Marie O'Hara ◽  
Bhushan N. Kharbikar ◽  
...  
Keyword(s):  
Bone Fracture ◽  
Fracture Repair ◽  
In Vivo Studies ◽  
Sustained Delivery ◽  
Mineral Density ◽  
Localized Delivery ◽  
Poly Ethylene ◽  
Tyrosine Receptor Kinase

Currently, there are no biological approaches to accelerate bone fracture repair. Osteobiologics that promote endochondral ossification are an exciting alternative to surgically implanted bone grafts, however, the translation of osteobiologics remains elusive because of the need for localized and sustained delivery that is both safe and effective. In this regard, an injectable system composed of hydrogel-based microparticles designed to release osteobiologics in a controlled and localized manner is ideal in the context of bone fracture repair. Here, we describe poly (ethylene glycol) dimethacrylate (PEGDMA)-based microparticles, in the form of microrods, engineered to be loaded with beta nerve growth factor (β-NGF) for use in a murine tibial fracture model. In-vitro studies demonstrated that protein-loading efficiency is readily altered by varying PEGDMA macromer concentration and that β-NGF loaded onto PEGDMA microrods exhibited sustained release over a period of 7 days. In-vitro bioactivity of β-NGF was confirmed using a tyrosine receptor kinase A (Trk-A) expressing cell line, TF-1. Moreover, TF-1 cell proliferation significantly increased when incubated with β-NGF loaded PEGDMA microrods versus β-NGF in media. In-vivo studies show that PEGDMA microrods injected into the fracture calluses of mice remained in the callus for over 7 days. Importantly, a single injection of β-NGF-loaded PEGDMA microrods resulted in significantly improved fracture healing as indicated by significant increases in bone volume, trabecular connective density, and bone mineral density and a significant decrease in cartilage despite a remarkably lower dose (~111 fold) than the β-NGF in media. In conclusion, we demonstrate a novel and translational method of delivering β-NGF via injectable PEGDMA microrods to improve bone fracture repair.

scholarly journals Biodegradable Antimicrobial Agent/Analgesic/Bone Morphogenetic Protein-Loaded Nanofibrous Fixators for Bone Fracture Repair

2021 ◽  
Author(s):  
Yi-Hsun Yu ◽  
Yu-Ting Lin ◽  
Yung-Heng Hsu ◽  
Ying-Chao Chou ◽  
Wen-Neng W. N. Ueng ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Bone Fracture ◽  
Antimicrobial Agents ◽  
Cartilage Damage ◽  
Fracture Repair ◽  
Bone Morphogenetic Protein 2 ◽  
Burst Release ◽  
Morphogenetic Protein

Abstract Background Post-operative infection and pain management are two critical aspects that are of great concern to orthopedic surgeons. Although there are several protocols available to deal with these issues, they are fraught with complications such as cartilage damage, cardiovascular and neurological intoxication, and systemic adverse responses. Therefore, it is necessary to develop safe and effective perioperative protocols. In the present study, antimicrobial agents/analgesics/growth factor-embedded biodegradable hybrid fixators (polycaprolactone fixator + poly[lactide-co-glycolide] sheath-core structured nanofibers) for bone fracture repair were designed. These fixators were fabricated using solution-extrusion three-dimensional printing and electrospinning. The in vitro and in vivo release of the incorporated vancomycin, ceftazidime, lidocaine, and bone morphogenetic protein-2 (BMP-2) was evaluated. The in vivo efficacy of the biomolecule-loaded nanofibrous fixators was investigated in rabbit rib-fracture models. Results The nanofibrous fixators were shown to release vancomycin, ceftazidime, and lidocaine in a sustained manner in both in vitro and in vivo conditions and protected BMP-2 from burst release. The implantation of these hybrid fixators around the fractured rib significantly improved animal activities and bone union indicating that the inclusion of analgesic in the fixator effectively reduced the post-surgical pain and thereby helped in recovery. Conclusions The novel biomolecule-loaded nanofibrous hybrid fixators resulted in excellent therapeutic outcomes. They may be effective in the repair of rib fractures in clinical settings and may help deal with surgical complications such as infection, non-union, and intolerable post-operative pain.

Crosslinked nanocarriers based upon poly(ethylene imine) for systemic plasmid delivery: In vitro characterization and in vivo studies in mice

2007 ◽  
Vol 118 (3) ◽  
pp. 370-380 ◽  
Author(s):  
Michael Neu ◽  
Oliver Germershaus ◽  
Shirui Mao ◽  
Karl-Heinz Voigt ◽  
Martin Behe ◽  
...  
Keyword(s):  
In Vivo Studies ◽  
Ethylene Imine ◽  
In Vitro Characterization ◽  
Poly Ethylene ◽  
Plasmid Delivery

scholarly journals Folate Receptor Targeted Imaging Using Poly (ethylene glycol)-folate: In Vitro and In Vivo Studies

2007 ◽  
Vol 22 (3) ◽  
pp. 405 ◽  
Author(s):  
Se-Lim Kim ◽  
Hwan-Jeong Jeong ◽  
Eun-Mi Kim ◽  
Chang-Moon Lee ◽  
Tae-Hyoung Kwon ◽  
...  
Keyword(s):  
Ethylene Glycol ◽  
Folate Receptor ◽  
In Vivo Studies ◽  
Targeted Imaging ◽  
Poly Ethylene Glycol ◽  
Poly Ethylene

Ondansetron-loaded biodegradable microspheres as a nasal sustained delivery system: In vitro/in vivo studies

2009 ◽  
Vol 00 (00) ◽  
pp. 090730043344010-8 ◽  
Author(s):  
Sevgi Gungor ◽  
Alper Okyar ◽  
Sidika Erturk-Toker ◽  
Gul Baktir ◽  
Yildiz Ozsoy
Keyword(s):  
Delivery System ◽  
In Vivo Studies ◽  
Biodegradable Microspheres ◽  
Sustained Delivery

Biodegradable Polymeric Nanoparticles for Tumor-Selective Tamoxifen Delivery: In Vitro and in Vivo Studies

2004 ◽  
Vol 845 ◽  
Author(s):  
Dinesh B. Shenoy ◽  
Jugminder S. Chawla ◽  
Mansoor M. Amiji
Keyword(s):  
Cellular Uptake ◽  
Polymeric Nanoparticles ◽  
Therapeutic Benefit ◽  
In Vivo Studies ◽  
Tumor Mass ◽  
Biodistribution Studies ◽  
Poly Ethylene ◽  
Surface Modified

1. ABSTRACT: This study was performed to evaluate the in-vitro and in-vivo tumor-cellular uptake and biodistribution pattern of tamoxifen when administered intravenously as a simple solution and upon encapsulation into biodegradable, surface-modified poly(ε-caprolactone) (PCL) nanoparticles. PCL (MW ∼ 15, 000) nanoparticles were prepared by the solvent displacement method and characterized for particle size/charge and surface morphology (by scanning electron microscopy). We investigated the nanoparticle-surface modification potential of the hydrophilic stabilizer (Pluronic® F-68 and F-108) employed during the preparation by electron spectroscopy for chemical analysis (ESCA). Quantitative in-vitro cellular uptake of tritiated (3H) tamoxifen in solution form and as nanoparticulate formulation was assessed in MCF-7 breast cancer cells. In-vivo biodistribution studies for the same formulations were carried out in Nu/Nu mice bearing MDA-MB-231 human breast carcinoma xenograft. Spherical nanoparticles having positive zeta potential (∼25 mV) were obtained in the size range of 200-300 nm. Pluronics (both F-68 and F-108), the triblock copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) induced surface hydrophilization of the nanoparticles via adsorption as evident by ESCA. Nanoparticulate formulations of tamoxifen achieved higher intracellular concentrations when exposed at therapeutic concentrations to tumor cells in-vitro compared to solutions. The in-vivo biodistribution studies carried out in nude mice bearing experimental breast tumor suggested increased tumor concentrations for the drug administered as nanoparticulate formulations besides longer retention times within tumor mass. This type of delivery system is expected to provide better therapeutic benefit by dual means: preferential concentration within the tumor mass via enhanced permeation and retention pathway, and; subsequent controlled release, thus maintaining the local drug concentration for longer periods of time to achieve maximal cell-kill.

Apigenin promotes osteogenic differentiation of mesenchymal stem cells and accelerates bone fracture healing via activating Wnt/β-catenin signaling

2021 ◽  
Author(s):  
Fei-fei Pan ◽  
Jiang Shao ◽  
Chuan-jian Shi ◽  
Zhi-peng Li ◽  
Wei-ming Fu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Fracture Healing ◽  
Osteogenic Differentiation ◽  
Bone Fracture ◽  
Fruits And Vegetables ◽  
Target Genes ◽  
Fracture Repair

Apigenin (API), a natural plant flavone, is abundantly found in common fruits and vegetables. As a bioactive flavonoid, API exhibits several activities including anti-proliferation and anti-inflammation. A recent study showed that API could retard osteoporosis progress, indicating its role in the skeletal system. However, the detailed function and mechanism remain obscure. In the present study, API was found to promote osteogenic differentiation of mesenchymal stem cells (MSCs). And further investigation showed that API could enhance the expression of the critical transcription factor β-catenin and several downstream target genes of Wnt signaling, thus activated Wnt/β-catenin signaling. Using a rat femoral fracture model, API was found to improve new bone formation and accelerate fracture healing in vivo. In conclusion, our data demonstrated that API could promote osteogenesis in vitro and facilitate the fracture healing in vivo via activating Wnt/β-catenin signaling, indicating that API may be a promising therapeutic candidate for bone fracture repair.

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