Skeletal tissue engineering—from in vitro studies to large animal models

Buma, P.; Schreurs, Wim; Verdonschot, Nico

doi:10.1016/s0142-9612(03)00492-7

Cited by 78 publications

(60 citation statements)

References 40 publications

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“…In contrast, xenografts are in plentiful supply but they carry even greater risks of immune rejection and in situ degeneration as well as disease transmission. Tissue engineering offers a promising alternative to permanent implants in the repair of damaged tissue, through the use of autologous stem cells seeded into a suitable scaffold (Ahsan and Nerem 2005;Blaker et al 2003;Buma et al 2004;Marot et al 2010). …”

Section: Introductionmentioning

confidence: 99%

Bone tissue engineering by using a combination of polymer/Bioglass composites with human adipose-derived stem cells

Kirkham

et al. 2014

Cell Tissue Res

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Translational research in bone tissue engineering is essential for 'bench to bedside' patient benefit. However, the idea combination of stem cells and biomaterial scaffolds for bone repair/regeneration is still unclear. The aim of this study was to investigate the osteogenic capacity of a combination of poly(DL-lactic acid) (PDLLA) porous foams containing 5 and 40 wt% of Bioglass ® particles with human adipose-derived stem cells (ADSCs) in vitro and in vivo. Live/dead fluorescent markers, confocal microscopy and scanning electron microscopy (SEM) showed that PDLLA/Bioglass ® porous scaffolds supported ADSCs attachment, growth and osteogenic differentiation, which were confirmed by enhanced alkaline phosphatase activity (ALP). Higher Bioglass ® content of the PDLLA foams increased more ALP activity compared to PDLLA only group. Extracellular matrix deposition after 8 weeks in in vitro culture was evident by Alcian blue/Sirius red staining.In vivo bone formation was assessed using scaffold/ADSCs constructs in diffusion chambers transplanted intraperitoneally into nude mice and recovered after 8 weeks.Histological and immunohistochemical assays indicated significant new bone formation in the 40 wt% and 5 wt% Bioglass ® constructs compared to the PDLLA only group. This study indicated the combination of a well-developed biodegradable bioactive porous PDLLA/Bioglass ® composite scaffold with a high potential stem cells source -human ADSCs could be a promising approach for bone regeneration in clinical setting.

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Section: Introductionmentioning

confidence: 99%

Bone tissue engineering by using a combination of polymer/Bioglass composites with human adipose-derived stem cells

Kirkham

et al. 2014

Cell Tissue Res

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“…Many differences, such as mineral density, healing capacity or the response to mechanical stimuli, exist in the bone metabolism of small animals when compared to that of humans (Egermann et al, 2005;Holy et al, 2000). Therefore it is questionable to extrapolate the in vivo results of small animals into the specific clinical situation of osteoporotic patients without pre-clinical tests in a large animal (Buma et al, 2004). To our knowledge, no data exists concerning local delivery of bisphophonate to increase fixation strength of an implant in a large osteoporotic animal model.…”

Section: Introductionmentioning

confidence: 99%

Implants delivering bisphosphonate locally increase periprosthetic bone density in an osteoporotic sheep model. A pilot study

Stadelmann¹,

Gauthier²,

Terrier³

et al. 2008

eCM

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It is a clinical challenge to obtain a sufficient orthopaedic implant fixation in weak osteoporotic bone. When the primary implant fixation is poor, micromotions occur at the bone-implant interface, activating osteoclasts, which leads to implant loosening. Bisphosphonate can be used to prevent the osteoclastic response, but when administered systemically its bioavailability is low and the time it takes for the drug to reach the periprosthetic bone may be a limiting factor. Recent data has shown that delivering bisphosphonate locally from the implant surface could be an interesting solution. Local bisphosphonate delivery increased periprosthetic bone density, which leads to a stronger implant fixation, as demonstrated in rats by the increased implant pullout force. The aim of the present study was to verify the positive effect on periprosthetic bone remodelling of local bisphosphonate delivery in an osteoporotic sheep model. Four implants coated with zoledronate and two control implants were inserted in the femoral condyle of ovariectomized sheep for 4 weeks. The bone at the implant surface was 50% higher in the zoledronate-group compared to control group. This effect was significant up to a distance of 400μm from the implant surface. The presented results are similar to what was observed in the osteoporotic rat model, which suggest that the concept of releasing zoledronate locally from the implant to increase the implant fixation is not species specific. The results of this trial study support the claim that local zoledronate could increase the fixation of an implant in weak bone.

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“…Furthermore, extrapolation of the results from one animal model to another may also decrease the number of experimentations as well as the costs related to the characterization of bone substitutes. 29 These animal models may also be used to answer fundamental questions on the osteointegrative properties of new substitutes or new approaches to bone tissue engineering. In fine, preclinical studies in animals should be performed with surgical techniques and loading conditions as close as possible to those used in humans.…”

Section: Introductionmentioning

confidence: 99%

Small‐animal models for testing macroporous ceramic bone substitutes

et al. 2004

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The aim of this study was to compare the bone colonization of a macroporous biphasic calcium phosphate (MBCP) ceramic in different sites (femur, tibia, and calvaria) in two animal species (rats and rabbits). A critical size defect model was used in all cases with implantation for 21 days. Bone colonization in the empty and MBCP-filled defects was measured with the use of backscattered electron microscopy (BSEM). In the empty cavities, bone healing remained on the edges, and did not bridge the critical size defects. Bone growth was observed in all the implantation sites in rats (approx. 13.6 -36.6% of the total defect area, with ceramic ranging from 46.1 to 51.9%). The bone colonization appeared statistically higher in the femur of rabbits (48.5%) than in the tibia (12.6%) and calvaria (22.9%) sites. This slightly higher degree of bone healing was related to differences in the bone architecture of the implantation sites. Concerning the comparison between animal species, bone colonization appeared greater in rabbits than in rats for the femoral site (48.5% vs. 29.6%). For the other two sites (the tibia and calvaria), there was no statistically significant difference. The increased bone ingrowth observed in rabbit femurs might be due to the large bone surface area in contact with the MBCP ceramics. The femoral epiphysis of rabbits is therefore a favorable model for testing the bone-bonding capacity of materials, but a comparison with other implantation sites is subject to bias. This study shows that well-conducted and fully validated models with the use of small animals are essential in the development of new bone substitutes.

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Skeletal tissue engineering—from in vitro studies to large animal models

Cited by 78 publications

References 40 publications

Bone tissue engineering by using a combination of polymer/Bioglass composites with human adipose-derived stem cells

Bone tissue engineering by using a combination of polymer/Bioglass composites with human adipose-derived stem cells

Implants delivering bisphosphonate locally increase periprosthetic bone density in an osteoporotic sheep model. A pilot study

Small‐animal models for testing macroporous ceramic bone substitutes

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