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Bone tissue engineering via nanostructured calcium phosphate biomaterials and stem cells.

Wang P, Zhao L, Liu J, Weir MD, Zhou X, Xu HH - Bone Res (2014)

Bottom Line: The interactions between stem cells and nano-CaP are highlighted, including cell attachment, orientation/morphology, differentiation and in vivo bone regeneration.Several trends can be seen: (i) nano-CaP biomaterials support stem cell attachment/proliferation and induce osteogenic differentiation, in some cases even without osteogenic supplements; (ii) the influence of nano-CaP surface patterns on cell alignment is not prominent due to non-uniform distribution of nano-crystals; (iii) nano-CaP can achieve better bone regeneration than conventional CaP biomaterials; (iv) combining stem cells with nano-CaP accelerates bone regeneration, the effect of which can be further enhanced by growth factors; and (v) cell microencapsulation in nano-CaP scaffolds is promising for bone tissue engineering.These understandings would help researchers to further uncover the underlying mechanisms and interactions in nano-CaP stem cell constructs in vitro and in vivo, tailor nano-CaP composite construct design and stem cell type selection to enhance cell function and bone regeneration, and translate laboratory findings to clinical treatments.

View Article: PubMed Central - PubMed

Affiliation: Biomaterials & Tissue Engineering Division, Department of Endodontics, Prosthodontics and Operative Dentistry, University of Maryland Dental School , Baltimore, MD 21201, USA ; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University , Chengdu, Sichuan 610041, China.

ABSTRACT
Tissue engineering is promising to meet the increasing need for bone regeneration. Nanostructured calcium phosphate (CaP) biomaterials/scaffolds are of special interest as they share chemical/crystallographic similarities to inorganic components of bone. Three applications of nano-CaP are discussed in this review: nanostructured calcium phosphate cement (CPC); nano-CaP composites; and nano-CaP coatings. The interactions between stem cells and nano-CaP are highlighted, including cell attachment, orientation/morphology, differentiation and in vivo bone regeneration. Several trends can be seen: (i) nano-CaP biomaterials support stem cell attachment/proliferation and induce osteogenic differentiation, in some cases even without osteogenic supplements; (ii) the influence of nano-CaP surface patterns on cell alignment is not prominent due to non-uniform distribution of nano-crystals; (iii) nano-CaP can achieve better bone regeneration than conventional CaP biomaterials; (iv) combining stem cells with nano-CaP accelerates bone regeneration, the effect of which can be further enhanced by growth factors; and (v) cell microencapsulation in nano-CaP scaffolds is promising for bone tissue engineering. These understandings would help researchers to further uncover the underlying mechanisms and interactions in nano-CaP stem cell constructs in vitro and in vivo, tailor nano-CaP composite construct design and stem cell type selection to enhance cell function and bone regeneration, and translate laboratory findings to clinical treatments.

No MeSH data available.


Bone regeneration via CPC scaffolds containing hiPSC-MSCs, hUCMSCs and hBMSCs, and CPC without cells. (a–d) H&E; staining of stem cell-seeded CPC implanted in critical-sized cranial defects in nude rats. (e) Histomorphometry analysis of new bone area fraction. Bars with dissimilar marks (# and *) indicate values that are significantly different from each other (P<0.05). Each value is mean±s.d. (n=6). Scaffolds containing hiPSC-MSCs, hUCMSCs and hBMSCs exhibited better bone regeneration than CPC control without cells. There was no significant difference between hUCMSC and hBMSC groups (P>0.1).
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fig3: Bone regeneration via CPC scaffolds containing hiPSC-MSCs, hUCMSCs and hBMSCs, and CPC without cells. (a–d) H&E; staining of stem cell-seeded CPC implanted in critical-sized cranial defects in nude rats. (e) Histomorphometry analysis of new bone area fraction. Bars with dissimilar marks (# and *) indicate values that are significantly different from each other (P<0.05). Each value is mean±s.d. (n=6). Scaffolds containing hiPSC-MSCs, hUCMSCs and hBMSCs exhibited better bone regeneration than CPC control without cells. There was no significant difference between hUCMSC and hBMSC groups (P>0.1).

Mentions: Therefore, combining stem cells with nano-CaP scaffolds can greatly enhance bone regeneration. Regarding the types of stem cells, hBMSCs are the gold standard in stem cell-based bone regeneration and have been successfully used in clinics.99 However, the use of hBMSCs is hampered by an invasive procedure to harvest, limited availability, donor site morbidity, and loss of potency of stem cells obtained from seniors and patients with diseases and disorders.100 Therefore, other stem cell sources are critically needed for bone regeneration. Currently, there are three broad types of stem cells: adult stem cells, ESCs and iPSCs. Adult stem cells can be found in stem cell niches such as bone marrow, adipose tissue, umbilical cord, placenta, etc. They exhibit a lineage-restricted differentiation potential and exhibit multipotency.101 In contrast, ESCs and iPSCs can give rise to cell types of all three germ layers, which is known as pluripotency. This feature makes these stem cells an extremely valuable and potent cell source. ESCs are obtained from the inner cell mass of blastocysts, while iPSCs are derived from reprogramming of somatic differentiated cells.102 hESCs involve complex cell culture procedures, risks of tumorigenicity and ethical concerns. Patient-specific hiPSCs with similar proliferation and differentiation ability to hESCs has the potential to overcome some of these hurdles. Thus, iPSCs are potentially the new frontier for cell-based regenerative medicine research. Several studies focused on the comparison of various types of stem cells in combination with nano-CaP biomaterials to repair bone defects. Chen et al.103 compared the in vivo bone regeneration efficiency of hUCMSCs and hBMSCs on a nano-crystalline CPC–chitosan–RGD scaffold in a nude rat cranial bone defect model. It was found that the bone-forming ability of hUCMSC–CPC constructs matched that of hBMSC–CPC constructs. 103 Our recent study revealed that, when seeded on macroporous CPC scaffolds, hiPSC-MSCs had good osteogenic capability comparable to hUCMSCs and the gold-standard hBMSCs (Figure 3). After implanting stem cell–CPC constructs in critical-sized cranial defects in rats, the new bone area fraction at 12 weeks for hiPSC-MSC–CPC constructs was (30.4±5.8)%, which was 2.8-fold the (11.0±6.3)% of CPC control without cell seeding (P<0.05). No significant differences in new bone area fraction were detected among hiPSC-MSCs, hUCMSCs and hBMSCs groups (P>0.1). The new bone exhibited an organized morphology which is typical of mature bone, manifested by the appearance of bone matrix with osteocytes and blood vessels, and with newly formed bone being lined by osteoblasts (Figure 4). Thus, hiPSC-MSCs and hUCMSCs may represent viable alternatives to hBMSCs and hESCs for bone regeneration. Reddy et al.104 compared MSCs from four different sources (human placenta, umbilical cord, fetal bone marrow and adipose tissue), cultured in the presence of nanosized biphasic ceramics. Placental MSCs demonstrated the best osteogenic potential based on expression of osteogenic markers and complete regeneration of bone defect in the femur of rats when seeded with nanoceramic with a Ca/P ratio of 1.58. Therefore, constructs using stem cells and nano-CaP scaffolds are highly promising for bone regeneration in vivo.


Bone tissue engineering via nanostructured calcium phosphate biomaterials and stem cells.

Wang P, Zhao L, Liu J, Weir MD, Zhou X, Xu HH - Bone Res (2014)

Bone regeneration via CPC scaffolds containing hiPSC-MSCs, hUCMSCs and hBMSCs, and CPC without cells. (a–d) H&E; staining of stem cell-seeded CPC implanted in critical-sized cranial defects in nude rats. (e) Histomorphometry analysis of new bone area fraction. Bars with dissimilar marks (# and *) indicate values that are significantly different from each other (P<0.05). Each value is mean±s.d. (n=6). Scaffolds containing hiPSC-MSCs, hUCMSCs and hBMSCs exhibited better bone regeneration than CPC control without cells. There was no significant difference between hUCMSC and hBMSC groups (P>0.1).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
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fig3: Bone regeneration via CPC scaffolds containing hiPSC-MSCs, hUCMSCs and hBMSCs, and CPC without cells. (a–d) H&E; staining of stem cell-seeded CPC implanted in critical-sized cranial defects in nude rats. (e) Histomorphometry analysis of new bone area fraction. Bars with dissimilar marks (# and *) indicate values that are significantly different from each other (P<0.05). Each value is mean±s.d. (n=6). Scaffolds containing hiPSC-MSCs, hUCMSCs and hBMSCs exhibited better bone regeneration than CPC control without cells. There was no significant difference between hUCMSC and hBMSC groups (P>0.1).
Mentions: Therefore, combining stem cells with nano-CaP scaffolds can greatly enhance bone regeneration. Regarding the types of stem cells, hBMSCs are the gold standard in stem cell-based bone regeneration and have been successfully used in clinics.99 However, the use of hBMSCs is hampered by an invasive procedure to harvest, limited availability, donor site morbidity, and loss of potency of stem cells obtained from seniors and patients with diseases and disorders.100 Therefore, other stem cell sources are critically needed for bone regeneration. Currently, there are three broad types of stem cells: adult stem cells, ESCs and iPSCs. Adult stem cells can be found in stem cell niches such as bone marrow, adipose tissue, umbilical cord, placenta, etc. They exhibit a lineage-restricted differentiation potential and exhibit multipotency.101 In contrast, ESCs and iPSCs can give rise to cell types of all three germ layers, which is known as pluripotency. This feature makes these stem cells an extremely valuable and potent cell source. ESCs are obtained from the inner cell mass of blastocysts, while iPSCs are derived from reprogramming of somatic differentiated cells.102 hESCs involve complex cell culture procedures, risks of tumorigenicity and ethical concerns. Patient-specific hiPSCs with similar proliferation and differentiation ability to hESCs has the potential to overcome some of these hurdles. Thus, iPSCs are potentially the new frontier for cell-based regenerative medicine research. Several studies focused on the comparison of various types of stem cells in combination with nano-CaP biomaterials to repair bone defects. Chen et al.103 compared the in vivo bone regeneration efficiency of hUCMSCs and hBMSCs on a nano-crystalline CPC–chitosan–RGD scaffold in a nude rat cranial bone defect model. It was found that the bone-forming ability of hUCMSC–CPC constructs matched that of hBMSC–CPC constructs. 103 Our recent study revealed that, when seeded on macroporous CPC scaffolds, hiPSC-MSCs had good osteogenic capability comparable to hUCMSCs and the gold-standard hBMSCs (Figure 3). After implanting stem cell–CPC constructs in critical-sized cranial defects in rats, the new bone area fraction at 12 weeks for hiPSC-MSC–CPC constructs was (30.4±5.8)%, which was 2.8-fold the (11.0±6.3)% of CPC control without cell seeding (P<0.05). No significant differences in new bone area fraction were detected among hiPSC-MSCs, hUCMSCs and hBMSCs groups (P>0.1). The new bone exhibited an organized morphology which is typical of mature bone, manifested by the appearance of bone matrix with osteocytes and blood vessels, and with newly formed bone being lined by osteoblasts (Figure 4). Thus, hiPSC-MSCs and hUCMSCs may represent viable alternatives to hBMSCs and hESCs for bone regeneration. Reddy et al.104 compared MSCs from four different sources (human placenta, umbilical cord, fetal bone marrow and adipose tissue), cultured in the presence of nanosized biphasic ceramics. Placental MSCs demonstrated the best osteogenic potential based on expression of osteogenic markers and complete regeneration of bone defect in the femur of rats when seeded with nanoceramic with a Ca/P ratio of 1.58. Therefore, constructs using stem cells and nano-CaP scaffolds are highly promising for bone regeneration in vivo.

Bottom Line: The interactions between stem cells and nano-CaP are highlighted, including cell attachment, orientation/morphology, differentiation and in vivo bone regeneration.Several trends can be seen: (i) nano-CaP biomaterials support stem cell attachment/proliferation and induce osteogenic differentiation, in some cases even without osteogenic supplements; (ii) the influence of nano-CaP surface patterns on cell alignment is not prominent due to non-uniform distribution of nano-crystals; (iii) nano-CaP can achieve better bone regeneration than conventional CaP biomaterials; (iv) combining stem cells with nano-CaP accelerates bone regeneration, the effect of which can be further enhanced by growth factors; and (v) cell microencapsulation in nano-CaP scaffolds is promising for bone tissue engineering.These understandings would help researchers to further uncover the underlying mechanisms and interactions in nano-CaP stem cell constructs in vitro and in vivo, tailor nano-CaP composite construct design and stem cell type selection to enhance cell function and bone regeneration, and translate laboratory findings to clinical treatments.

View Article: PubMed Central - PubMed

Affiliation: Biomaterials & Tissue Engineering Division, Department of Endodontics, Prosthodontics and Operative Dentistry, University of Maryland Dental School , Baltimore, MD 21201, USA ; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University , Chengdu, Sichuan 610041, China.

ABSTRACT
Tissue engineering is promising to meet the increasing need for bone regeneration. Nanostructured calcium phosphate (CaP) biomaterials/scaffolds are of special interest as they share chemical/crystallographic similarities to inorganic components of bone. Three applications of nano-CaP are discussed in this review: nanostructured calcium phosphate cement (CPC); nano-CaP composites; and nano-CaP coatings. The interactions between stem cells and nano-CaP are highlighted, including cell attachment, orientation/morphology, differentiation and in vivo bone regeneration. Several trends can be seen: (i) nano-CaP biomaterials support stem cell attachment/proliferation and induce osteogenic differentiation, in some cases even without osteogenic supplements; (ii) the influence of nano-CaP surface patterns on cell alignment is not prominent due to non-uniform distribution of nano-crystals; (iii) nano-CaP can achieve better bone regeneration than conventional CaP biomaterials; (iv) combining stem cells with nano-CaP accelerates bone regeneration, the effect of which can be further enhanced by growth factors; and (v) cell microencapsulation in nano-CaP scaffolds is promising for bone tissue engineering. These understandings would help researchers to further uncover the underlying mechanisms and interactions in nano-CaP stem cell constructs in vitro and in vivo, tailor nano-CaP composite construct design and stem cell type selection to enhance cell function and bone regeneration, and translate laboratory findings to clinical treatments.

No MeSH data available.