Promotion of Bone Regeneration Using Bioinspired PLGA/MH/ECM Scaffold Combined with Bioactive PDRN

Current approaches of biomaterials for the repair of critical-sized bone defects still require immense effort to overcome numerous obstacles. The biodegradable polymer-based scaffolds have been required to expand further function for bone tissue engineering. Poly(lactic-co-glycolic) acid (PLGA) is one of the most common biopolymers owing to its biodegradability for tissue regenerations. However, there are major clinical challenges that the byproducts of the PLGA cause an acidic environment of implanting site. The critical processes in bone repair are osteogenesis, angiogenesis, and inhibition of excessive osteoclastogenesis. In this study, the porous PLGA (P) scaffold was combined with magnesium hydroxide (MH, M) and bone-extracellular matrix (bECM, E) to improve anti-inflammatory ability and osteoconductivity. Additionally, the bioactive polydeoxyribonucleotide (PDRN, P) was additionally incorporated in the existing PME scaffold. The prepared PMEP scaffold has pro-osteogenic and pro-angiogenic effects and inhibition of osteoclast due to the PDRN, which interacts with the adenosine A2A receptor agonist that up-regulates expression of vascular endothelial growth factor (VEGF) and down-regulates inflammatory cytokines. The PMEP scaffold has superior biological properties for human bone-marrow mesenchymal stem cells (hBMSCs) adhesion, proliferation, and osteogenic differentiation in vitro. Moreover, the gene expressions related to osteogenesis and angiogenesis of hBMSCs increased and the inflammatory factors decreased on the PMEP scaffold. In conclusion, it provides a promising strategy and clinical potential candidate for bone tissue regeneration and repairing bone defects.

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Fabrication of High-Strength and Porous Hybrid Scaffolds Based on Nano-Hydroxyapatite and Human-Like Collagen for Bone Tissue Regeneration

Polymers ◽

10.3390/polym12010061 ◽

2020 ◽

Vol 12 (1) ◽

pp. 61 ◽

Cited By ~ 6

Author(s):

Yannan Liu ◽

Juan Gu ◽

Daidi Fan

Keyword(s):

Mechanical Properties ◽

Enzymatic Hydrolysis ◽

Bone Tissue ◽

Tissue Regeneration ◽

Bone Repair ◽

Three Dimensional ◽

High Strength ◽

Biological Properties ◽

Bone Tissue Regeneration

A novel, three-dimensional, porous, human-like collagen (HLC)/nano-hydroxyapatite (n-HA) scaffold cross-linked by 1,2,7,8-diepoxyoctane (DEO) was successfully fabricated, which showed excellent mechanical and superior biological properties for bone tissue regeneration in this study. The physicochemical characterizations of different n-HA/HLC/DEO (nHD) scaffolds were investigated by determining the morphology, compression stress, elastic modulus, Young’s modulus and enzymatic hydrolysis behavior in vitro. The results demonstrated that nHD-2 and nHD-3 scaffolds showed superior mechanical properties and resistance to enzymatic hydrolysis compared to nHD-1 scaffolds. The cell viability, live cell staining and cell adhesion analysis results demonstrated that nHD-2 scaffolds exhibited low cytotoxicity and excellent cytocompatibility compared with nHD-1 and nHD-3 scaffolds. Furthermore, subcutaneous injections of nHD-2 scaffolds in rabbits produced superior anti-biodegradation effects and histocompatibility compared with injections of nHD-1 and nHD-3 scaffolds after 1, 2 and 4 weeks. In addition, the repair of bone defects in rabbits demonstrated that nHD-2 scaffolds presented an improved ability for guided bone regeneration and reconstruction compared to commercially available bone scaffold composite hydroxyapatite/collagen (HC). Collectively, the results show that nHD-2 scaffolds show promise for application in bone tissue engineering due to their excellent mechanical properties, anti-biodegradation, anti-biodegradation, biocompatibility and bone repair effects.

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Cellularizing hydrogel-based scaffolds to repair bone tissue: How to create a physiologically relevant micro-environment?

Journal of Tissue Engineering ◽

10.1177/2041731417712073 ◽

2017 ◽

Vol 8 ◽

pp. 204173141771207 ◽

Cited By ~ 28

Author(s):

Mathieu Maisani ◽

Daniele Pezzoli ◽

Olivier Chassande ◽

Diego Mantovani

Keyword(s):

Bone Regeneration ◽

Bone Tissue ◽

Bone Repair ◽

Critical Issue ◽

Bone Defects ◽

Bone Tissue Regeneration ◽

Differentiation Potential ◽

Promising Alternative

Tissue engineering is a promising alternative to autografts or allografts for the regeneration of large bone defects. Cell-free biomaterials with different degrees of sophistication can be used for several therapeutic indications, to stimulate bone repair by the host tissue. However, when osteoprogenitors are not available in the damaged tissue, exogenous cells with an osteoblast differentiation potential must be provided. These cells should have the capacity to colonize the defect and to participate in the building of new bone tissue. To achieve this goal, cells must survive, remain in the defect site, eventually proliferate, and differentiate into mature osteoblasts. A critical issue for these engrafted cells is to be fed by oxygen and nutrients: the transient absence of a vascular network upon implantation is a major challenge for cells to survive in the site of implantation, and different strategies can be followed to promote cell survival under poor oxygen and nutrient supply and to promote rapid vascularization of the defect area. These strategies involve the use of scaffolds designed to create the appropriate micro-environment for cells to survive, proliferate, and differentiate in vitro and in vivo. Hydrogels are an eclectic class of materials that can be easily cellularized and provide effective, minimally invasive approaches to fill bone defects and favor bone tissue regeneration. Furthermore, by playing on their composition and processing, it is possible to obtain biocompatible systems with adequate chemical, biological, and mechanical properties. However, only a good combination of scaffold and cells, possibly with the aid of incorporated growth factors, can lead to successful results in bone regeneration. This review presents the strategies used to design cellularized hydrogel-based systems for bone regeneration, identifying the key parameters of the many different micro-environments created within hydrogels.

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Dual Network Composites of Poly(vinyl alcohol)-Calcium Metaphosphate/Alginate with Osteogenic Ions for Bone Tissue Engineering in Oral and Maxillofacial Surgery

Bioengineering ◽

10.3390/bioengineering8080107 ◽

2021 ◽

Vol 8 (8) ◽

pp. 107

Author(s):

Lilis Iskandar ◽

Lucy DiSilvio ◽

Jonathan Acheson ◽

Sanjukta Deb

Keyword(s):

Tissue Engineering ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Vinyl Alcohol ◽

Maxillofacial Surgery ◽

Bone Defects ◽

Bone Tissue Regeneration ◽

Poly Vinyl Alcohol ◽

Oral And Maxillofacial Surgery

Despite considerable advances in biomaterials-based bone tissue engineering technologies, autografts remain the gold standard for rehabilitating critical-sized bone defects in the oral and maxillofacial (OMF) region. A majority of advanced synthetic bone substitutes (SBS’s) have not transcended the pre-clinical stage due to inferior clinical performance and translational barriers, which include low scalability, high cost, regulatory restrictions, limited advanced facilities and human resources. The aim of this study is to develop clinically viable alternatives to address the challenges of bone tissue regeneration in the OMF region by developing ‘dual network composites’ (DNC’s) of calcium metaphosphate (CMP)—poly(vinyl alcohol) (PVA)/alginate with osteogenic ions: calcium, zinc and strontium. To fabricate DNC’s, single network composites of PVA/CMP with 10% (w/v) gelatine particles as porogen were developed using two freeze–thawing cycles and subsequently interpenetrated by guluronate-dominant sodium alginate and chelated with calcium, zinc or strontium ions. Physicochemical, compressive, water uptake, thermal, morphological and in vitro biological properties of DNC’s were characterised. The results demonstrated elastic 3D porous scaffolds resembling a ‘spongy bone’ with fluid absorbing capacity, easily sculptable to fit anatomically complex bone defects, biocompatible and osteoconductive in vitro, thus yielding potentially clinically viable for SBS alternatives in OMF surgery.

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Enhancing in vitro bioactivity and in vivo osteogenesis of organic–inorganic nanofibrous biocomposites with novel bioceramics

Journal of Materials Chemistry B ◽

10.1039/c4tb00889h ◽

2014 ◽

Vol 2 (37) ◽

pp. 6293-6305 ◽

Cited By ~ 15

Author(s):

Tao Liu ◽

Xinbo Ding ◽

Dongzhi Lai ◽

Yongwei Chen ◽

Ridong Zhang ◽

...

Keyword(s):

Bone Tissue ◽

Tissue Regeneration ◽

Biological Properties ◽

Bone Tissue Regeneration ◽

In Vitro Bioactivity ◽

Physicochemical And Biological Properties

MGHA-introduced, an electrospun SF-based composite can exhibit improved physicochemical and biological properties to stimulate bone tissue regeneration and repair.

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Conducting PEEK Nanocomposites with Electrophoretically Deposited Bioactive Coating for Bone Tissue Regeneration and Multi-Modal Therapeutic Applications

10.26434/chemrxiv.13166717 ◽

2020 ◽

Author(s):

Miaomiao He ◽

Ce zhu ◽

Huan Xu ◽

dan Sun ◽

Chen Chen ◽

...

Keyword(s):

Bone Tissue ◽

Tissue Regeneration ◽

Bone Repair ◽

Graphene Nanosheets ◽

Biomechanical Properties ◽

Bone Diseases ◽

Bone Tissue Regeneration ◽

Order Of Magnitude

The use of polyetheretherketone (PEEK) has grown exponentially in the biomedical field in recent decades due to its outstanding biomechanical properties. However, its lack of bioactivity/osteointegration remains an unresolved issue towards its wide use in orthopedic applications. In this work, graphene nanosheets have been incorporated into PEEK to obtain multifunctional nanocomposites. Due to the formation of electrical percolation network and the π-π* conjugation between graphene and PEEK, the resulting composites have achieved twelve order of magnitude enhancement in its electrical conductivity, and have enabled electrophoretic deposition of bioactive/anti-bacterial coating consisting of stearyltrimethylammonium chloride (STAC) modified hydroxyapatite (HA). The coated composite implant showed significant boosting of BMSC cell proliferation in vitro. In addition, the strong photothermal conversion effect of the graphene nanofillers have enabled laser induced heating of our nanocomposite implants, where the temperature of the implant can reach 45 oC in 150 s. The unique multi-functionality of our composite implant has also been demonstrated for photothermal applications such as enhancing bacterial (E. coli and S. aureus) eradication and tumor cell (MG63) inhibition, as well as bone tissue regeneration in vivo. The results suggest the strong potential of our multi-functional implant in bone repair applications as well as multi-modal therapy of challenging bone diseases such as osteosarcoma and osteomyelitis

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Icaritin Enhancing Bone Formation Initiated by Sub-Microstructured Calcium Phosphate Ceramic for Critical Size Defect Repair

Frontiers in Materials ◽

10.3389/fmats.2020.598057 ◽

2020 ◽

Vol 7 ◽

Author(s):

Haitao Peng ◽

Jianxiao Li ◽

Yanan Xu ◽

Guoyu Lv

Keyword(s):

Calcium Phosphate ◽

Bone Formation ◽

Bone Tissue ◽

Tissue Regeneration ◽

Bone Defects ◽

Bone Tissue Regeneration ◽

Calcium Phosphate Ceramic ◽

Dose Dependent

Adequate bone tissue regeneration has been challenging to achieve at critical-sized bone defects caused by disease. Bone tissue engineering using a combination of scaffolds and bioactive factors provides new hope for the treatment of this extreme condition. Icaritin, a herb-derived chemical, has shown its ability to enhance bone formation both in vitro and in vivo, and it has been found that sub-micron surface structure instructs bone formation in calcium phosphate ceramics (CaPs). Here, we evaluated the possibility of using a submicron surface structured CaP ceramic as the carrier of icaritin for bone tissue regeneration in critical-sized bone defects. Icaritin, an herb-derived chemical, was loaded into a submicron surface structured porous calcium phosphate ceramic (Ø12.8 × 3 mm) to get samples with 0, 10, 50, 250, and 1,250 µg icaritin per CaP disc (M0, M10, M50, M250, M1250 groups, respectively). In vitro evaluation with the certain dosages correlated to those released from the samples showed a dose-dependent enhancement of osteogenic differentiation and mineralization of human bone marrow stromal cells with the presence of osteogenic factors in the culture medium, indicating icaritin is an osteopromotive factor. After intramuscular implantation of the samples in dogs for 8 weeks, a dose-dependent of bone formation was seen with enhanced bone formation at the dosage of 50 and 250 µg. To evaluate the in vivo osteogenic potentials of icaritin-containing CaP ceramic scaffolds in the orthopedic site, a 12.8 mm calvarial defect model in rabbits was established. Micro-computed tomography (micro-CT) and histology results at weeks 4, 8 and 12 post-surgery showed more newly formed bone in M250 group, with correspondingly more new vessel ingrowth. The results presented herein suggested that being osteopromotive, icaritin could enhance bone formation initiated by sub-microstructured CaP ceramics and the CaP ceramics scaffold incorporating icaritin is a promising biomaterial for the treatment of critical-sized defect.

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Developing a novel magnesium calcium phosphate/sodium alginate composite cement with high strength and proper self-setting time for bone repair

Journal of Biomaterials Applications ◽

10.1177/08853282211021535 ◽

2021 ◽

pp. 088532822110215

Author(s):

Haosheng He ◽

Haohao Ren ◽

Zhengwen Ding ◽

Mizhi Ji ◽

Hong Chen ◽

...

Keyword(s):

Calcium Phosphate ◽

Sodium Alginate ◽

Bone Repair ◽

Setting Time ◽

High Strength ◽

Biological Properties ◽

Mouse Bone Marrow ◽

Marrow Mesenchymal Stem Cells ◽

Composite Cements

In this work, novel magnesium calcium phosphate/sodium alginate composite cements were successfully fabricated with a proper setting time (5–24 min) and high compressive strength (91.1 MPa). The physicochemical and biological properties of the cement in vitro were fully characterized. The composite cements could gradually degrade in PBS as the soaking time increase, and the weight loss reached 20.74% by the end of 56th day. The cements could induce the deposition of Ca–P layer in SBF. Cell experiments proved that the extracts of the composite cements can effectively promote the proliferation and differentiation of the mouse bone marrow mesenchymal stem cells (MSCs). These preliminary results indicate that the magnesium calcium phosphate/sodium alginate composite cements could be promising as potential bone repair candidate materials.

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Chitosan-alginate Hybrid Scaffolds for in Vitro Bone Tissue Regeneration

MRS Proceedings ◽

10.1557/proc-873-k8.2 ◽

2005 ◽

Vol 873 ◽

Author(s):

Zhensheng Li ◽

Hassna R. Ramay ◽

Kip D. Hauch ◽

Miqin Zhang

Keyword(s):

Bone Tissue ◽

Porous Scaffold ◽

Mechanical Test ◽

Biological Properties ◽

Bone Tissue Regeneration ◽

High Porosity ◽

Thermally Induced ◽

Mineral Deposition ◽

Alginate Scaffold

AbstractThis paper reports the development of a biodegradable porous scaffold made from naturally derived chitosan and alginate polymers for bone tissue engineering. The scaffold has a 3-D interconnected porous structure and was fabricated through thermally induced phase separation. The mechanical test showed that the scaffold has compressive strength of 0.46 ± 0.02 MPa — about 4 times that of the pure chitosan scaffold. The cell-material interaction study indicated that osteoblast cells seeded on the chitosan-alginate scaffold attach and proliferate well. The mineral deposition occurred after 3 days of culture and formed large chunks after 7 days. The chitosan-alginate scaffold was also found to have desirable swelling property and was structurally stable in solutions of different pH. The chitosan-alginate scaffold can be prepared from solutions of neutral pH allowing growth factors to be incorporated homogeneously into the scaffold for sustained release. This research demonstrated a technique by which a polymer-based biodegradable scaffold can be made to have high porosity up to 92% and excellent mechanical and biological properties.

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Octacalcium Phosphate for Bone Tissue Engineering: Synthesis, Modification, and In Vitro Biocompatibility Assessment

International Journal of Molecular Sciences ◽

10.3390/ijms222312747 ◽

2021 ◽

Vol 22 (23) ◽

pp. 12747

Author(s):

Anastasia Yu. Teterina ◽

Igor V. Smirnov ◽

Irina S. Fadeeva ◽

Roman S. Fadeev ◽

Polina V. Smirnova ◽

...

Keyword(s):

Low Temperature ◽

Bone Tissue ◽

Bone Repair ◽

Calcium Phosphates ◽

Normal Pressure ◽

Octacalcium Phosphate ◽

Biological Properties ◽

In Vitro Biocompatibility ◽

Ionic Substitution

Octacalcium phosphate (OCP, Ca8H2(PO4)6·5H2O) is known to be a possible precursor of biological hydroxyapatite formation of organic bone tissue. OCP has higher biocompatibility and osseointegration rate compared to other calcium phosphates. In this work, the synthesis of low-temperature calcium phosphate compounds and substituted forms of those at physiological temperatures is shown. Strontium is used to improve bioactive properties of the material. Strontium was inserted into the OCP structure by ionic substitution in solutions. The processes of phase formation of low-temperature OCP with theoretical substitution of strontium for calcium up to 50 at.% in conditions close to physiological, i.e., temperature 35–37 °C and normal pressure, were described. The effect of strontium substitution range on changes in the crystal lattice of materials, the microstructural features, surface morphology and biological properties in vitro has been established. The results of the study indicate the effectiveness of using strontium in OCP for improving biocompatibility of OCP based composite materials intended for bone repair.

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