Growth factor-loaded scaffolds for bone engineering

Jansen, John A.; Vehof, J.W.M.; Ruhé, P. Quinten; Kroeze-Deutman, H.; Kuboki, Yoshinori; Takita, Hiroko; Hedberg, Elizabeth L.; Mikos, Antonios G.

doi:10.1016/j.jconrel.2004.07.005

Cited by 180 publications

(119 citation statements)

References 40 publications

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“…Ruhe et al (2005b) showed bioactive factors to be incorporated into (PLGA/ Ca-P cement) composites and could be slowly released. Furthermore, the combination of osteogenic growth factor release (BMP-2) from polymer scaffolds such as PLA and the addition of preosteogenic cells have further increased the possibility of engineering bone (Rose et al, 2004;Yang et al, 2004;Montjovent et al, 2005;Montjovent et al, 2007;Georgiou et al, 2007), whilst Jansen et al (2005) demonstrated orthotopic bone formation in a rabbit cranial defect model stimulated in rhTGFβ1 and rhBMP-2 CaP cement and Titanium-fibre mesh scaffolds.…”

Section: Skeletal Tissue Engineering the Clinical Need For New Bonementioning

confidence: 99%

“…Recent developments in bioengineering scaffold design have led to growth factors to be incorporated onto or entrapped within the scaffolds. (Murphy et al, 2000;Murphy et al, 2004;Yang et al, 2004;Huang et al, 2005a;Huang et al, 2005b;Jansen et al, 2005;Kaigler et al, 2006a;Leach et al, 2006;Oest et al, 2007;Jeon et al, 2007;Kanczler et al, 2007;Wei et al, 2007;Tai et al, 2007;Chang et al, 2007). As these scaffolds are biodegradable, bioactive factors can be released locally over a period of time.…”

Section: Skeletal Tissue Engineering the Clinical Need For New Bonementioning

confidence: 99%

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Osteogenesis and angiogenesis: The potential for engineering bone

Kanczler

Oreffo²

2008

eCM

887

637

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The repair of large bone defects remains a major clinical orthopaedic challenge. Bone is a highly vascularised tissue reliant on the close spatial and temporal connection between blood vessels and bone cells to maintain skeletal integrity. Angiogenesis thus plays a pivotal role in skeletal development and bone fracture repair. Current procedures to repair bone defects and to provide structural and mechanical support include the use of grafts (autologous, allogeneic) or implants (polymeric or metallic). These approaches face significant limitations due to insufficient supply, potential disease transmission, rejection, cost and the inability to integrate with the surrounding host tissue.

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Section: Skeletal Tissue Engineering the Clinical Need For New Bonementioning

confidence: 99%

Section: Skeletal Tissue Engineering the Clinical Need For New Bonementioning

confidence: 99%

Osteogenesis and angiogenesis: The potential for engineering bone

Kanczler

Oreffo²

2008

eCM

887

637

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“…Owing to the rapid advances in recombinant technology and the availability of large scale manufacturing of cytokines and growth factors, many recent tissue engineering strategies have turned to the use of specific growth factors to stimulate cellular activity in vitro and for improved functional neotissue formation in vivo [2][3][4][5]. Importantly, the delivery mode appears to be critical for the application of these factors in tissue engineering [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

“…The release kinetics can be modulated by adjusting the factor loading, polymer molecular weight, lactide / glycolide ratio in the copolymer, and formulation methods [21,23,26,27]. Notably, the biological activity of the released factors can be largely maintained during the encapsulation process and upon release [5,21]. However, in terms of tissue engineering applications, it is preferable that a tissue engineering construct serves as both a factor delivery carrier and as a 3-dimensional (3-D) scaffold for cellular activities.…”

Section: Introductionmentioning

confidence: 99%

Nano-fibrous scaffold for controlled delivery of recombinant human PDGF-BB

Wei

Jin

Giannobile

et al. 2006

Journal of Controlled Release

202

157

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The localized and temporally controlled delivery of growth factors is key to achieving optimal clinical efficacy. In sophisticated tissue engineering strategies, the biodegradable scaffold is preferred to serve as both a three-dimensional (3-D) substrate and a growth factor delivery vehicle to promote cellular activity and enhance tissue neogenesis. This study presents a novel approach to fabricate tissue engineering scaffolds capable of controlled growth factor delivery whereby growth factor containing microspheres were incorporated into 3-D scaffolds with good mechanical properties, wellinterconnected macroporous and nano-fibrous structures. The microspheres were uniformly distributed throughout the nano-fibrous scaffold and their incorporation did not interfere the macro-, micro-, and nanostructures of the scaffold. The release kinetics of platelet-derived growth factor-BB (PDGF-BB) from microspheres and scaffolds was investigated using poly(lactic-co-glycolic acid) (PLGA50) microspheres with different molecular weights (6.5 and 64kDa, respectively) and microsphere-incorporated poly(L-lactic acid) (PLLA) nano-fibrous scaffolds. Incorporation of microspheres into scaffolds significantly reduced the initial burst release. Sustained release from several days to months was achieved through different microspheres in scaffolds. Released PDGF-BB was demonstrated to possess biological activity as evidenced by stimulation of human gingival fibroblast DNA synthesis in vitro. The successful generation of 3-D nano-fibrous scaffold incorporating controlled-release factors indicates significant potential for more complex tissue regeneration.

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“…[27][28][29][30] They are also a good system to delivery drug or growth factor for bone tissue engineering. 31,32 However, for a prefabricated bioceramic to fit into a bone cavity, the surgeon needs to machine the graft or carve the surgical site, leading to increases in bone loss, trauma, and surgical time. 3 On the other hand, injectable scaffolds can be used in minimally invasive procedures and fit intimately into bone defects.…”

mentioning

confidence: 99%

Human Embryonic Stem Cell-Derived Mesenchymal Stem Cell Seeding on Calcium Phosphate Cement-Chitosan-RGD Scaffold for Bone Repair

Chen

Zhou

Weir

et al. 2013

Tissue Engineering Part A

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Calcium phosphate cement (CPC) has in situ-setting ability and excellent osteoconductivity. Human embryonic stem cells (hESCs) are exciting for regenerative medicine due to their strong proliferative ability and multilineage differentiation capability. However, there has been no report on hESC seeding with CPC. The objectives of this study were to obtain hESC-derived mesenchymal stem cells (hESCd-MSCs), and to investigate hESCd-MSC proliferation and osteogenic differentiation on novel CPC with chitosan immobilized with RGD (CPC-chitosan-RGD). RGD was covalently bonded with chitosan, which was then incorporated into CPC. The CPC-chitosan-RGD scaffold had higher strength and toughness than CPC-chitosan control without RGD ( p < 0.05). hESCs were cultured to form embryoid bodies (EBs), and the MSCs were then migrated out of the EBs. Flow cytometry indicated that the hESCd-MSCs expressed typical surface antigen profile of MSCs. hESCd-MSCs had good viability when seeded on CPC scaffolds. The percentage of live cells and the cell density were significantly higher on CPC-chitosan-RGD than CPC-chitosan control. Scanning electron microscope examination showed hESCd-MSCs with a healthy spreading morphology adherent to CPC. hESCd-MSCs expressed high levels of osteogenic markers, including alkaline phosphatase, osteocalcin, collagen I, and Runx2. The mineral synthesis by the hESCd-MSCs on the CPC-chitosan-RGD scaffold was twice that for CPC-chitosan control. In conclusion, hESCs were successfully seeded on CPC scaffolds for bone tissue engineering. The hESCd-MSCs had good viability and osteogenic differentiation on the novel CPC-chitosan-RGD scaffold. RGD incorporation improved the strength and toughness of CPC, and greatly enhanced the hESCd-MSC attachment, proliferation, and bone mineral synthesis. Therefore, the hESCd-MSC-seeded CPC-chitosan-RGD construct is promising to improve bone regeneration in orthopedic and craniofacial applications.

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Growth factor-loaded scaffolds for bone engineering

Cited by 180 publications

References 40 publications

Osteogenesis and angiogenesis: The potential for engineering bone

Osteogenesis and angiogenesis: The potential for engineering bone

Nano-fibrous scaffold for controlled delivery of recombinant human PDGF-BB

Human Embryonic Stem Cell-Derived Mesenchymal Stem Cell Seeding on Calcium Phosphate Cement-Chitosan-RGD Scaffold for Bone Repair

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