Mesoporous bioactive glasses: structure characteristics, drug/growth factor delivery and bone regeneration application

The impact of bone diseases and trauma in the whole world has increased significantly in the past decades. Bioactive glasses are regarded as an important bone regeneration material owing to their generally excellent osteoconductivity and osteostimulativity. A new class of bioactive glass, referred to as mesoporous bioglass (MBG), was developed 7 years ago, which possess a highly ordered mesoporous channel structure and a highly specific surface area. The study of MBG for drug/growth factor delivery and bone tissue engineering has grown significantly in the past several years. In this article, we review the recent advances of MBG materials, including the preparation of different forms of MBG, composition–structure relationship, efficient drug/growth factor delivery and bone tissue engineering application. By summarizing our recent research, the interaction of MBG scaffolds with bone-forming cells, the effect of drug/growth factor delivery on proliferation and differentiation of tissue cells and the in vivo osteogenesis of MBG scaffolds are highlighted. The advantages and limitations of MBG for drug delivery and bone tissue engineering have been compared with microsize bioactive glasses and nanosize bioactive glasses. The future perspective of MBG is discussed for bone regeneration application by combining drug delivery with bone tissue engineering and investigating the in vivo osteogenesis mechanism in large animal models.

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Advances in Growth Factor Delivery for Bone Tissue Engineering

International Journal of Molecular Sciences ◽

10.3390/ijms22020903 ◽

2021 ◽

Vol 22 (2) ◽

pp. 903

Author(s):

Érica Resende Oliveira ◽

Lei Nie ◽

Daria Podstawczyk ◽

Ahmad Allahbakhsh ◽

Jithendra Ratnayake ◽

...

Keyword(s):

Tissue Engineering ◽

Extracellular Matrix ◽

Growth Factors ◽

Growth Factor ◽

Bone Tissue Engineering ◽

Bone Regeneration ◽

Bone Tissue ◽

Bone Repair ◽

Bone Diseases ◽

Growth Factor Delivery

Shortcomings related to the treatment of bone diseases and consequent tissue regeneration such as transplants have been addressed to some extent by tissue engineering and regenerative medicine. Tissue engineering has promoted structures that can simulate the extracellular matrix and are capable of guiding natural bone repair using signaling molecules to promote osteoinduction and angiogenesis essential in the formation of new bone tissues. Although recent studies on developing novel growth factor delivery systems for bone repair have attracted great attention, taking into account the complexity of the extracellular matrix, scaffolding and growth factors should not be explored independently. Consequently, systems that combine both concepts have great potential to promote the effectiveness of bone regeneration methods. In this review, recent developments in bone regeneration that simultaneously consider scaffolding and growth factors are covered in detail. The main emphasis in this overview is on delivery strategies that employ polymer-based scaffolds for spatiotemporal-controlled delivery of both single and multiple growth factors in bone-regeneration approaches. From clinical applications to creating alternative structural materials, bone tissue engineering has been advancing constantly, and it is relevant to regularly update related topics.

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Collagen Scaffolds Containing Hydroxyapatite-CaO Fiber Fragments for Bone Tissue Engineering

Polymers ◽

10.3390/polym12051174 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1174 ◽

Cited By ~ 1

Author(s):

Shiao-Wen Tsai ◽

Sheng-Siang Huang ◽

Wen-Xin Yu ◽

Yu-Wei Hsu ◽

Fu-Yin Hsu

Keyword(s):

Tissue Engineering ◽

Bone Tissue Engineering ◽

Bone Regeneration ◽

Bone Tissue ◽

Drug Loading ◽

Sol Gel ◽

Regeneration Ability ◽

Burst Release ◽

Electrospinning Technique

Collagen (COL) and hydroxyapatite (HAp) are the major components of bone, therefore, COL-HAp composites have been widely used as bone substitutes to promote bone regeneration. We have reported that HAp-CaO fibers (HANFs), which were fabricated by a sol-gel route followed by an electrospinning technique, possessed good drug-loading efficiency and limited the burst release of tetracycline. In the present study, we used HANF fragments to evaluate the effects of COL-HANF scaffolds on MG63 osteoblast-like cell behaviors. COL-HANF composite scaffolds in which the average diameter of HANFs was approximately 461 ± 186 nm were fabricated by a freeze-drying process. The alkaline phosphatase activity and the protein expression levels of OCN and BSP showed that compared with COL alone, the COL-HANF scaffold promoted the differentiation of MG63 osteoblast-like cells. In addition, the bone regeneration ability of the COL-HANF scaffold was examined by using a rabbit condylar defect model in vivo. The COL-HANF scaffold was biodegradable and promoted bone regeneration eight weeks after the operation. Hence, we concluded that the COL-HANF scaffold has potential as a bone graft for bone tissue engineering.

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Calcium phosphate ceramic systems in growth factor and drug delivery for bone tissue engineering: A review

Acta Biomaterialia ◽

10.1016/j.actbio.2011.11.017 ◽

2012 ◽

Vol 8 (4) ◽

pp. 1401-1421 ◽

Cited By ~ 536

Author(s):

Susmita Bose ◽

Solaiman Tarafder

Keyword(s):

Drug Delivery ◽

Tissue Engineering ◽

Growth Factor ◽

Calcium Phosphate ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Calcium Phosphate Ceramic

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Double-layered microsphere based dual growth factor delivery system for guided bone regeneration

RSC Advances ◽

10.1039/c8ra02072h ◽

2018 ◽

Vol 8 (30) ◽

pp. 16503-16512 ◽

Cited By ~ 5

Author(s):

Chun Xu ◽

Jia Xu ◽

Lan Xiao ◽

Zhihao Li ◽

Yin Xiao ◽

...

Keyword(s):

Drug Delivery ◽

Tissue Engineering ◽

Growth Factor ◽

Bone Regeneration ◽

Delivery System ◽

Drug Delivery Systems ◽

Guided Bone Regeneration ◽

Delivery Systems ◽

Growth Factor Delivery ◽

Dual Growth Factor Delivery

Microsphere based drug delivery systems show great advantages for tissue engineering.

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Human DPSCs fabricate vascularized woven bone tissue: a new tool in bone tissue engineering

Clinical Science ◽

10.1042/cs20170047 ◽

2017 ◽

Vol 131 (8) ◽

pp. 699-713 ◽

Cited By ~ 46

Author(s):

Francesca Paino ◽

Marcella La Noce ◽

Alessandra Giuliani ◽

Alfredo De Rosa ◽

Serena Mazzoni ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Growth Factor ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Dental Pulp ◽

3D Structure ◽

Growth Curves ◽

Woven Bone

Human dental pulp stem cells (hDPSCs) are mesenchymal stem cells that have been successfully used in human bone tissue engineering. To establish whether these cells can lead to a bone tissue ready to be grafted, we checked DPSCs for their osteogenic and angiogenic differentiation capabilities with the specific aim of obtaining a new tool for bone transplantation. Therefore, hDPSCs were specifically selected from the stromal–vascular dental pulp fraction, using appropriate markers, and cultured. Growth curves, expression of bone-related markers, calcification and angiogenesis as well as an in vivo transplantation assay were performed. We found that hDPSCs proliferate, differentiate into osteoblasts and express high levels of angiogenic genes, such as vascular endothelial growth factor and platelet-derived growth factor A. Human DPSCs, after 40 days of culture, give rise to a 3D structure resembling a woven fibrous bone. These woven bone (WB) samples were analysed using classic histology and synchrotron-based, X-ray phase-contrast microtomography and holotomography. WB showed histological and attractive physical qualities of bone with few areas of mineralization and neovessels. Such WB, when transplanted into rats, was remodelled into vascularized bone tissue. Taken together, our data lead to the assumption that WB samples, fabricated by DPSCs, constitute a noteworthy tool and do not need the use of scaffolds, and therefore they are ready for customized regeneration.

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An ECM-Mimicking, Mesenchymal Stem Cell-Embedded Hybrid Scaffold for Bone Regeneration

BioMed Research International ◽

10.1155/2017/8591073 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 10

Author(s):

Jozafina Haj ◽

Tharwat Haj Khalil ◽

Mizied Falah ◽

Eyal Zussman ◽

Samer Srouji

Keyword(s):

Tissue Engineering ◽

Extracellular Matrix ◽

Bone Tissue Engineering ◽

Bone Regeneration ◽

Bone Tissue ◽

Bone Repair ◽

Dorsal Side ◽

Human Mscs ◽

Hybrid Scaffold

While biologically feasible, bone repair is often inadequate, particularly in cases of large defects. The search for effective bone regeneration strategies has led to the emergence of bone tissue engineering (TE) techniques. When integrating electrospinning techniques, scaffolds featuring randomly oriented or aligned fibers, characteristic of the extracellular matrix (ECM), can be fabricated. In parallel, mesenchymal stem cells (MSCs), which are capable of both self-renewing and differentiating into numerous tissue types, have been suggested to be a suitable option for cell-based tissue engineering therapies. This work aimed to create a novel biocompatible hybrid scaffold composed of electrospun polymeric nanofibers combined with osteoconductive ceramics, loaded with human MSCs, to yield a tissue-like construct to promote in vivo bone formation. Characterization of the cell-embedded scaffolds demonstrated their resemblance to bone tissue extracellular matrix, on both micro- and nanoscales and MSC viability and integration within the electrospun nanofibers. Subcutaneous implantation of the cell-embedded scaffolds in the dorsal side of mice led to new bone, muscle, adipose, and connective tissue formation within 8 weeks. This hybrid scaffold may represent a step forward in the pursuit of advanced bone tissue engineering scaffolds.

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Immobilization of Murine Anti-BMP-2 Monoclonal Antibody on Various Biomaterials for Bone Tissue Engineering

BioMed Research International ◽

10.1155/2014/940860 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 9

Author(s):

Sahar Ansari ◽

Marcelo O. Freire ◽

Eun-Kyoung Pang ◽

Alaa I. Abdelhamid ◽

Mohammad Almohaimeed ◽

...

Keyword(s):

Tissue Engineering ◽

Bone Formation ◽

Bone Tissue Engineering ◽

Bone Regeneration ◽

Bone Tissue ◽

De Novo ◽

Isotype Control ◽

Different Types ◽

Calvarial Defects

Biomaterials are widely used as scaffolds for tissue engineering. We have developed a strategy for bone tissue engineering that entails application of immobilized anti-BMP-2 monoclonal antibodies (mAbs) to capture endogenous BMPs in vivo and promote antibody-mediated osseous regeneration (AMOR). The purpose of the current study was to compare the efficacy of immobilization of a specific murine anti-BMP-2 mAb on three different types of biomaterials and to evaluate their suitability as scaffolds for AMOR. Anti-BMP-2 mAb or isotype control mAb was immobilized on titanium (Ti) microbeads, alginate hydrogel, and ACS. The treated biomaterials were surgically implanted in rat critical-sized calvarial defects. After 8 weeks,de novobone formation was assessed using micro-CT and histomorphometric analyses. Results showedde novobone regeneration with all three scaffolds with immobilized anti-BMP-2 mAb, but not isotype control mAb. Ti microbeads showed the highest volume of bone regeneration, followed by ACS. Alginate showed the lowest volume of bone. Localization of BMP-2, -4, and -7 antigens was detected on all 3 scaffolds with immobilized anti-BMP-2 mAb implanted in calvarial defects. Altogether, these data suggested a potential mechanism for bone regeneration through entrapment of endogenous BMP-2, -4, and -7 proteins leading to bone formation using different types of scaffoldsviaAMOR.

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Sequential growth factor delivery from complexed microspheres for bone tissue engineering

Biomaterials ◽

10.1016/j.biomaterials.2008.07.017 ◽

2008 ◽

Vol 29 (31) ◽

pp. 4195-4204 ◽

Cited By ~ 150

Author(s):

F. Buket Basmanav ◽

Gamze T. Kose ◽

Vasif Hasirci

Keyword(s):

Tissue Engineering ◽

Growth Factor ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Growth Factor Delivery

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Low level laser therapy promotes bone regeneration by coupling angiogenesis and osteogenesis

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02493-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Jie Bai ◽

Lijun Li ◽

Ni Kou ◽

Yuwen Bai ◽

Yaoyang Zhang ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Bone Tissue Engineering ◽

Bone Regeneration ◽

Bone Tissue ◽

Low Level Laser Therapy ◽

Level Laser ◽

Vascularized Bone

Abstract Background Bone tissue engineering is a new concept bringing hope for the repair of large bone defects, which remains a major clinical challenge. The formation of vascularized bone is key for bone tissue engineering. Growth of specialized blood vessels termed type H is associated with bone formation. In vivo and in vitro studies have shown that low level laser therapy (LLLT) promotes angiogenesis, fracture healing, and osteogenic differentiation of stem cells by increasing reactive oxygen species (ROS). However, whether LLLT can couple angiogenesis and osteogenesis, and the underlying mechanisms during bone formation, remains largely unknown. Methods Mouse bone marrow mesenchymal stem cells (BMSCs) combined with biphasic calcium phosphate (BCP) grafts were implanted into C57BL/6 mice to evaluate the effects of LLLT on the specialized vessel subtypes and bone regeneration in vivo. Furthermore, human BMSCs and human umbilical vein endothelial cells (HUVECs) were co-cultured in vitro. The effects of LLLT on cell proliferation, angiogenesis, and osteogenesis were assessed. Results LLLT promoted the formation of blood vessels, collagen fibers, and bone tissue and also increased CD31hiEMCNhi-expressing type H vessels in mBMSC/BCP grafts implanted in mice. LLLT significantly increased both osteogenesis and angiogenesis, as well as related gene expression (HIF-1α, VEGF, TGF-β) of grafts in vivo and of co-cultured BMSCs/HUVECs in vitro. An increase or decrease of ROS induced by H2O2 or Vitamin C, respectively, resulted in an increase or decrease of HIF-1α, and a subsequent increase and decrease of VEGF and TGF-β in the co-culture system. The ROS accumulation induced by LLLT in the co-culture system was significantly decreased when HIF-1α was inhibited with DMBPA and was followed by decreased expression of VEGF and TGF-β. Conclusions LLLT enhanced vascularized bone regeneration by coupling angiogenesis and osteogenesis. ROS/HIF-1α was necessary for these effects of LLLT. LLLT triggered a ROS-dependent increase of HIF-1α, VEGF, and TGF-β and resulted in subsequent formation of type H vessels and osteogenic differentiation of mesenchymal stem cells. As ROS also was a target of HIF-1α, there may be a positive feedback loop between ROS and HIF-1α, which further amplified HIF-1α induction via the LLLT-mediated ROS increase. This study provided new insight into the effects of LLLT on vascularization and bone regeneration in bone tissue engineering.

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