Bone tissue engineering using polyetherketoneketone scaffolds combined with autologous mesenchymal stem cells in a sheep calvarial defect model

Adamzyk, Carina; Kachel, Paul; Hoß, Mareike; Gremse, Felix; Modabber, Ali; Hölzle, Frank; Tolba, René; Neuß, Sabine; Lethaus, Bernd

doi:10.1016/j.jcms.2016.04.012

Cited by 61 publications

(60 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among the large animals, sheep are an ideal model for bone tissue engineering (Guo et al, ; Pobloth et al, ; Sanjurjo‐Rodríguez et al, ) and have been proposed for a wide range of applications in biomedical research (Adamzyk et al, ; Delling, Brehma, Ludewigb, Winterc, & Jülkec, ; Scheerlinck, Snibson, Bowles, & Sutton, ; Sill et al, ). Sheep are used to test the efficacy of MSCs in different bone's pathologies because evidence proves that their skeletal structure has a higher resemblance to the human one as compared to mice and rabbits (Kalaszczynska et al, ; O'Loughlin et al, ; Pearce, Richards, Milz, Schneider, & Pearce, ; Petite et al, ).…”

Section: Introductionmentioning

confidence: 99%

Autocrine signals increase ovine mesenchymal stem cells migration through Aquaporin‐1 and CXCR4 overexpression

Pelagalli¹,

Nardelli

Lucarelli

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

Sheep is a relevant large animal model that is frequently used to test innovative tissue engineering (TE) approaches especially for bone reconstruction. Mesenchymal stem cells (MSCs) are used in TE applications because they represent key component of adult tissue repair. Importantly, MSCs from different species show similar characteristics, which facilitated their application in translational studies using animal models. Nowadays, many researches are focusing on the use of ovine mesenchymal stem cells (oMSCs) in orthopedic preclinical settings for regenerative medicine purposes. Therefore, there is a need to amplify our knowledge on the mechanisms underlying the behaviour of these cells. Recently, several studies have shown that MSC function is largely dependent on factors that MSCs release in the environment, as well as, in conditioned medium (CM). It has been demonstrated that MSCs through autocrine and paracrine signals are able to stimulate proliferation, migration, and differentiation of different type of cells including themselves. In this study, we investigated the effects of the CM produced by oMSCs on oMSCs themselves and we explored the signal pathways involved. We observed that CM caused an enhancement of oMSC migration. Furthermore, we found that CM increased levels of two membrane proteins involved in cell migration, Aquaporin 1 (AQP1), and C-X-C chemokine receptor type 4 (CXCR4), and activated Akt and Erk intracellular signal pathways. In conclusion, taken together our results suggest the high potential of autologous CM as a promising tool to modulate behaviour of MSCs thus improving their use in therapeutically approaches.

show abstract

Section: Introductionmentioning

confidence: 99%

Autocrine signals increase ovine mesenchymal stem cells migration through Aquaporin‐1 and CXCR4 overexpression

Pelagalli¹,

Nardelli

Lucarelli

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…Although autologous bone grafts are a gold standard and allograft options are extensively used to treat bone defects in the clinical setting, they have their own drawbacks [1–3], including donor-side morbidity and increased operation time [4]. A synthetic bone substitute as an alternative solution holds great promise to treat large bone defects, and has been extensively studied over the past decades [5–7].…”

Section: Introductionmentioning

confidence: 99%

Engineering biomimetic periosteum with β-TCP scaffolds to promote bone formation in calvarial defects of rats

Zhang

Gao

et al. 2017

Stem Cell Res Ther

View full text Add to dashboard Cite

BackgroundThere is a critical need for the management of large bone defects. The purpose of this study was to engineer a biomimetic periosteum and to combine this with a macroporous β-tricalcium phosphate (β-TCP) scaffold for bone tissue regeneration.MethodsRat bone marrow-derived mesenchymal stem cells (rBMSCs) were harvested and cultured in different culture media to form undifferentiated rBMSC sheets (undifferentiated medium (UM)) and osteogenic cell sheets (osteogenic medium (OM)). Simultaneously, rBMSCs were differentiated to induced endothelial-like cells (iECs), and the iECs were further cultured on a UM to form a vascularized cell sheet. At the same time, flow cytometry was used to detect the conversion rates of rBMSCs to iECs. The pre-vascularized cell sheet (iECs/UM) and the osteogenic cell sheet (OM) were stacked together to form a biomimetic periosteum with two distinct layers, which mimicked the fibrous layer and cambium layer of native periosteum. The biomimetic periostea were wrapped onto porous β-TCP scaffolds (BP/β-TCP) and implanted in the calvarial bone defects of rats. As controls, autologous periostea with β-TCP (AP/β-TCP) and β-TCP alone were implanted in the calvarial defects of rats, with a no implantation group as another control. At 2, 4, and 8 weeks post-surgery, implants were retrieved and X-ray, microcomputed tomography (micro-CT), histology, and immunohistochemistry staining analyses were performed.ResultsFlow cytometry results showed that rBMSCs were partially differentiated into iECs with a 35.1% conversion rate in terms of CD31. There were still 20.97% rBMSCs expressing CD90. Scanning electron microscopy (SEM) results indicated that cells from the wrapped cell sheet on the β-TCP scaffold apparently migrated into the pores of the β-TCP scaffold. The histology and immunohistochemistry staining results from in vivo implantation indicated that the BP/β-TCP and AP/β-TCP groups promoted the formation of blood vessels and new bone tissues in the bone defects more than the other two control groups. In addition, micro-CT showed that more new bone tissue formed in the BP/β-TCP and AP/β-TCP groups than the other groups.ConclusionsInducing rBMSCs to iECs could be a good strategy to obtain an endothelial cell source for prevascularization. Our findings indicate that the biomimetic periosteum with porous β-TCP scaffold has a similar ability to promote osteogenesis and angiogenesis in vivo compared to the autologous periosteum. This function could result from the double layers of biomimetic periosteum. The prevascularized cell sheet served a mimetic fibrous layer and the osteogenic cell sheet served a cambium layer of native periosteum. The biomimetic periosteum with a porous ceramic scaffold provides a new promising method for bone healing.

show abstract

“…Moreover, one recent controlled study reported superior bone regeneration following AC repair with non‐induced BMSC‐loaded HA scaffolds, compared to the gold standard, that is AB grafts (Khalifa & Nowair, ). Nevertheless, since the current pre‐clinical evidence from large‐animal models is also conflicting (Adamzyk et al., ; Corbella et al., ), no clear conclusions can be drawn regarding the benefits of osteogenic pre‐differentiation of MSCs.…”

Section: Discussionmentioning

confidence: 99%

Cell therapy for orofacial bone regeneration: A systematic review and meta‐analysis

Shanbhag

Suliman

Pandis

et al. 2019

J Clinic Periodontology

View full text Add to dashboard Cite

Aim The objective of the present review was to answer the focused question: what is the effect of cell therapy in terms of orofacial bone regeneration compared to grafting with only biomaterial scaffolds and/or autogenous bone? Methods Electronic databases were searched for relevant controlled clinical and pre‐clinical (large‐animal) studies. Separate meta‐analyses of quantitative data regarding histological or radiographic new bone formation were performed. Results Forty‐seven eligible clinical and 57 pre‐clinical studies were included. Clinical studies were categorized based on the use of “minimally manipulated” whole tissues (e.g., bone marrow) or ex vivo expanded cells from “uncommitted” (bone marrow, adipose tissue) or “committed” sources (periosteum, bone). Based on limited and heterogeneous clinical evidence, implantation of cells (mostly whole bone marrow), in combination with biomaterial scaffolds results in bone regeneration which is (a) superior compared to implantation of scaffolds alone in sinus and horizontal ridge augmentation, and (b) comparable to autogenous bone in alveolar cleft repair. Conclusions Although current evidence points to the benefits of cell therapy in certain clinical indications, it is unclear whether the use of ex vivo expanded cells, either uncommitted or committed, is superior to whole tissue fractions in terms of bone regeneration. The relatively larger effect sizes in favour of cell therapy observed in pre‐clinical studies are diminished in clinical trials. Future controlled studies should include cost‐effectiveness analyses to guide clinical decision‐making.

show abstract

Bone tissue engineering using polyetherketoneketone scaffolds combined with autologous mesenchymal stem cells in a sheep calvarial defect model

Cited by 61 publications

References 44 publications

Autocrine signals increase ovine mesenchymal stem cells migration through Aquaporin‐1 and CXCR4 overexpression

Autocrine signals increase ovine mesenchymal stem cells migration through Aquaporin‐1 and CXCR4 overexpression

Engineering biomimetic periosteum with β-TCP scaffolds to promote bone formation in calvarial defects of rats

Cell therapy for orofacial bone regeneration: A systematic review and meta‐analysis

Contact Info

Product

Resources

About