The use of ASCs engineered to express BMP2 or TGF-β3 within scaffold constructs to promote calvarial bone repair

Lin, Chin-Yu; Chang, Yu‐Han; Li, Kuei-Chang; Lu, Chueng-He; Sung, Li‐Yu; Yeh, Chia-Lin; Lin, Kun‐Ju; Huang, Shiu-Feng; Yen, Tzu‐Chen; Hu, Yu‐Chen

doi:10.1016/j.biomaterials.2013.08.051

Cited by 83 publications

(68 citation statements)

References 50 publications

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“…More recently, adipose tissue was proposed as an alternative source of mesenchymal cells, i.e. adipose derived stem cells (ASCs), which have been employed in osteogenic models with contrasting results (Chou, Zuk, Chang, Benhaim, & Wu, 2011;Lin et al, 2013;P. A. Zuk et al, 2001;P.…”

Section: The Need For Osteogenesis: Osteoblast and Osteocyte Culturesmentioning

confidence: 99%

Overcoming physical constraints in bone engineering: ‘the importance of being vascularized’

et al. 2015

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Bone plays several physiological functions and is the second most commonly transplanted tissue after blood. Since the treatment of large bone defects is still unsatisfactory, researchers have endeavoured to obtain scaffolds able to release growth and differentiation factors for mesenchimal stem cells, osteoblasts and endothelial cells in order to obtain faster mineralization and prompt a reliable vascularization.Nowadays, the application of osteoblastic cultures spans from cell physiology and pharmacology to cytocompatibility measurement and osteogenic potential evaluation of novel biomaterials. To overcome the simple traditional monocultures in vitro, co-cultures of osteogenic and vasculogenic precursors were introduced with very interesting results. Increasingly complex culture systems have been developed, where cells are seeded on proper scaffolds and stimulated so as to mimic the physiological conditions more accurately. These bioreactors aim at enabling bone regeneration by incorporating different cells types into bioinspired materials within a surveilled habitat.This review is focused on the most recent developments in the organomimetic cultures of osteoblasts and vascular endothelial cells for bone tissue engineering.

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Section: The Need For Osteogenesis: Osteoblast and Osteocyte Culturesmentioning

confidence: 99%

Overcoming physical constraints in bone engineering: ‘the importance of being vascularized’

et al. 2015

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“…Improvements have been made in the characterisation and the stimulation of ASCs towards the osteogenic lineage and there have been increasing successful reports of the clinical use of ASCs in mandibular bone defects [113,114]. More recently, ASCs engineered to express BMP have been successfully used in vivo and clinically [112,113]. Clinical studies are required to investigate if they can be successfully used for orthopaedic weight-bearing and nonweight-bearing applications.…”

Section: Resultsmentioning

confidence: 98%

“…(2014) 14(11) The use of HA nanocomposite with ASCs and transduction with BMP-2 can enable healing of rabbit critical-sized defect radial defect [111]. There is further evidence to suggest that ASCs engineered to express BMP-2 combined with PGLA scaffolds can trigger better bone healing, switching the ossification pathway and significantly augmenting calvarial healing than ASCs engineered to express TGF-b in a rabbit model ( Table 2) [112].…”

Section: In Vivo Studiesmentioning

confidence: 96%

Skeletal tissue engineering using mesenchymal or embryonic stem cells: clinical and experimental data

Gamie

Macfarlane

Tomkinson

et al. 2014

Expert Opinion on Biological Therapy

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Enhanced results have been found when combining bone marrow-derived mesenchymal stem cells (BMMSCs) with recently developed scaffolds such as glass ceramics and starch-based polymeric scaffolds. Preclinical studies investigating adipose tissue-derived stem cells and umbilical cord tissue-derived stem cells suggest that they are likely to become promising alternatives. Stem cells derived from periosteum and dental tissues such as the periodontal ligament have an osteogenic potential similar to BMMSCs. Stem cells from human fetal bone marrow have demonstrated superior proliferation and osteogenic differentiation than perinatal and postnatal tissues. Despite ethical concerns and potential for teratoma formation, developments have also been made for the use of ESCs in terms of culture and ideal scaffold.

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“…Adipose-derived stem cells and mesenchymal stem cells naturally secrete relevant GFs for bone healing in response to cues from the microenvironment-such as hypoxia or ischemia-and reduce secretion once bone is healed. These cells can also be genetically engineered ex vivo to maintain an increased secretion profile of a specific GF through a variety of gene delivery strategies, including transfection via nucleofection, and viral and nonviral delivery vectors [31,[82][83][84] (reviewed in detail, specifically for BMP gene transfection, by Wilson et al [110]). Such cell-based therapies are limited by the tendency of the implanted cells to migrate away from the defect site or be cleared by the host.…”

Section: Cells As Drug-eluting Systemsmentioning

confidence: 99%

“…Once they are released from these encrypted sites, the half-life of Osteogenic, chondrogenic differentiation [4,28,31] growth factors in vivo is short-on the order of several minutes-due to enzymatic degradation, chemical and physical deactivation, and degradation processes such as hydrolysis, oxidation, isomerization, and aggregation [44,45]. Therefore, one of the most critical challenges in scaffold-based growth factor delivery is maintaining native protein conformation and bioactivity throughout scaffold loading and for the duration of in vivo release [46].…”

Section: Growth Factor Incorporation Strategiesmentioning

confidence: 99%

Growth factor-eluting technologies for bone tissue engineering

Nyberg

Holmes

Witham

et al. 2015

Drug Deliv. and Transl. Res.

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Growth factors are essential orchestrators of the normal bone fracture healing response. For non-union defects, delivery of exogenous growth factors to the injured site significantly improves healing outcomes. However, current clinical methods for scaffold-based growth factor delivery are fairly rudimentary, and there is a need for greater spatial and temporal regulation to increase their in vivo efficacy. Various approaches used to provide spatiotemporal control of growth factor delivery from bone tissue engineering scaffolds include physical entrapment, chemical binding, surface modifications, biomineralization, micro- and nanoparticle encapsulation, and genetically engineered cells. Here, we provide a brief review of these technologies, describing the fundamental mechanisms used to regulate release kinetics. Examples of their use in pre-clinical studies are discussed, and their capacities to provide tunable, growth factor delivery are compared. These advanced scaffold systems have the potential to provide safer, more effective therapies for bone regeneration than the systems currently employed in the clinic.

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The use of ASCs engineered to express BMP2 or TGF-β3 within scaffold constructs to promote calvarial bone repair

Cited by 83 publications

References 50 publications

Overcoming physical constraints in bone engineering: ‘the importance of being vascularized’

Overcoming physical constraints in bone engineering: ‘the importance of being vascularized’

Skeletal tissue engineering using mesenchymal or embryonic stem cells: clinical and experimental data

Growth factor-eluting technologies for bone tissue engineering

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