Tissue engineering and regenerative approaches to improving the healing of large bone defects

Verrier, Sophie; Alini, Mauro; Alsberg, Eben; Buchman, Steven R.; Kelly, Daniel J.; Laschke, Matthias W.; Menger, Michael D.; Murphy, William L.; Stegemann, Jan P.; Schütz, Michael; Miclau, Theodore; Stoddart, Martin J.; Evans, Christopher H.

doi:10.22203/ecm.v032a06

Cited by 87 publications

(64 citation statements)

References 232 publications

(186 reference statements)

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“…The wound-healing capacity of MSCs has led to studies in tissue engineering and regenerative medicine, such as seeding MSCs onto scaffolds to repair critical-sized bony defects (10). Scaffolds provide a three-dimensional structure to mechanically stimulate MSCs to undergo osteogenic differentiation or to secrete paracrine factors (10–13). Together, these studies suggest that MSCs may have potential applications in the repair of fractures and bony defects (10–13).…”

Section: Mesenchymal Stem Cells (Mscs)mentioning

confidence: 99%

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The Effects of Endocrine Disruptors on Adipogenesis and Osteogenesis in Mesenchymal Stem Cells: A Review

et al. 2017

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Endocrine-disrupting chemicals (EDCs) are prevalent in the environment, and epidemiologic studies have suggested that human exposure is linked to chronic diseases, such as obesity and diabetes. In vitro experiments have further demonstrated that EDCs promote changes in mesenchymal stem cells (MSCs), leading to increases in adipogenic differentiation, decreases in osteogenic differentiation, activation of pro-inflammatory cytokines, increases in oxidative stress, and epigenetic changes. Studies have also shown alteration in trophic factor production, differentiation ability, and immunomodulatory capacity of MSCs, which have significant implications to the current studies exploring MSCs for tissue engineering and regenerative medicine applications and the treatment of inflammatory conditions. Thus, the consideration of the effects of EDCs on MSCs is vital when determining potential therapeutic uses of MSCs, as increased exposure to EDCs may cause MSCs to be less effective therapeutically. This review focuses on the adipogenic and osteogenic differentiation effects of EDCs as these are most relevant to the therapeutic uses of MSCs in tissue engineering, regenerative medicine, and inflammatory conditions. This review will highlight the effects of EDCs, including organophosphates, plasticizers, industrial surfactants, coolants, and lubricants, on MSC biology.

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Section: Mesenchymal Stem Cells (Mscs)mentioning

confidence: 99%

“…Scaffolds provide a three-dimensional structure to mechanically stimulate MSCs to undergo osteogenic differentiation or to secrete paracrine factors (10–13). Together, these studies suggest that MSCs may have potential applications in the repair of fractures and bony defects (10–13). …”

Section: Mesenchymal Stem Cells (Mscs)mentioning

confidence: 99%

The Effects of Endocrine Disruptors on Adipogenesis and Osteogenesis in Mesenchymal Stem Cells: A Review

et al. 2017

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“…Bone tissue possesses a unique ability for self‐repair in response to minor injuries or trauma (Fröhlich et al, ). However, the healing of large bone defects, which are above a critical size, remains an unmet clinical need in modern orthopaedics (Verrier et al, ). Bone tissue engineering (BTE) aims to facilitate and accelerate the body's natural healing capacity via the use of biomaterial scaffolds, which encourage autologous host cells to proliferate, differentiate, and instigate the repair process.…”

Section: Introductionmentioning

confidence: 99%

Rapid healing of a critical‐sized bone defect using a collagen‐hydroxyapatite scaffold to facilitate low dose, combinatorial growth factor delivery

Walsh

Raftery

Chen

et al. 2019

J Tissue Eng Regen Med

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The healing of large, critically sized bone defects remains an unmet clinical need in modern orthopaedic medicine. The tissue engineering field is increasingly using biomaterial scaffolds as 3D templates to guide the regenerative process, which can be further augmented via the incorporation of recombinant growth factors. Typically, this necessitates supraphysiological doses of growth factor to facilitate an adequate therapeutic response. Herein, we describe a cell‐free, biomaterial implant which is functionalised with a low dose, combinatorial growth factor therapy that is capable of rapidly regenerating vascularised bone tissue within a critical‐sized rodent calvarial defect. Specifically, we demonstrate that the dual delivery of the growth factors bone morphogenetic protein‐2 (osteogenic) and vascular endothelial growth factor (angiogenic) at a low dose (5 μg/scaffold) on an osteoconductive collagen‐hydroxyapatite scaffold is highly effective in healing these critical‐sized bone defects. The high affinity between the hydroxyapatite component of this biomimetic scaffold and the growth factors functions to sequester them locally at the defect site. Using this growth factor‐loaded scaffold, we show complete bridging of a critical‐sized calvarial defect in all specimens at a very early time point of 4 weeks, with a 28‐fold increase in new bone volume and seven‐fold increase in new bone area compared with a growth factor‐free scaffold. Overall, this study demonstrates that a collagen‐hydroxyapatite scaffold can be used to locally harness the synergistic relationship between osteogenic and angiogenic growth factors to rapidly regenerate bone tissue without the need for more complex controlled delivery vehicles or high total growth factor doses.

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“…Modern biomaterials are supposed to function as degradable, osteoconductive scaffolds. They should not only induce bone formation at the bone‐graft‐interface via attraction and binding of cells, moreover they should enable bone and vascular ingrowth . Requirements for modern biomaterials are partially contradictory: need for high primary stability on the one hand and necessity of macroporosity in combination with degradability on the other hand .…”

Section: Introductionmentioning

confidence: 99%

“…They should not only induce bone formation at the bone‐graft‐interface via attraction and binding of cells, moreover they should enable bone and vascular ingrowth . Requirements for modern biomaterials are partially contradictory: need for high primary stability on the one hand and necessity of macroporosity in combination with degradability on the other hand . By way of example, scaffolds based on a combination of natural biopolymers with calcium phosphate‐based inorganic materials are bioactive and degradable.…”

Section: Introductionmentioning

confidence: 99%

Effect of bone sialoprotein coated three‐dimensional printed calcium phosphate scaffolds on primary human osteoblasts

et al. 2018

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The combination of the two techniques of rapid prototyping 3D-plotting and bioactive surface functionalization is presented, with emphasis on the in vitro effect of Bone Sialoprotein (BSP) on primary human osteoblasts (hOBs). Our primary objective was to demonstrate the BSP influence on the expression of distinctive osteoblast markers in hOBs. Secondary objectives included examinations of the scaffolds' surface and the stability of BSP-coating as well as investigations of cell viability and proliferation. 3D-plotted calcium phosphate cement (CPC) scaffolds were coated with BSP via physisorption. hOBs were seeded on the coated scaffolds, followed by cell viability measurements, gene expression analysis and visualization. Physisorption is an effective method for BSP-coating. Coating with higher BSP concentrations leads to enhanced BSP release. Two BSP concentrations (50 and 200 μg/mL) were examined in this study. The lower BSP concentration (50 µg/mL) decreased ALP and SPARC expression, whereas the higher BSP concentration (200 μg/mL) did not change gene marker expression. Enhanced cell viability was observed on BSP-coated scaffolds on day 3. hOBs developed a polygonal shape and connected in an intercellular network under BSP influence. Quantitative cell morphology analyses demonstrated for BSP-coated CPCs an enhanced cell area and reduced circularity. The strength of the above-mentioned effects of BSP-coated scaffolds in vivo is unknown, and future work is focusing on bone ingrowth and vascularization in vivo. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2565-2575, 2018.

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Tissue engineering and regenerative approaches to improving the healing of large bone defects

Cited by 87 publications

References 232 publications

The Effects of Endocrine Disruptors on Adipogenesis and Osteogenesis in Mesenchymal Stem Cells: A Review

The Effects of Endocrine Disruptors on Adipogenesis and Osteogenesis in Mesenchymal Stem Cells: A Review

Rapid healing of a critical‐sized bone defect using a collagen‐hydroxyapatite scaffold to facilitate low dose, combinatorial growth factor delivery

Effect of bone sialoprotein coated three‐dimensional printed calcium phosphate scaffolds on primary human osteoblasts

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