Marine Collagen Scaffolds for Nasal Cartilage Repair: Prevention of Nasal Septal Perforations in a New Orthotopic Rat Model Using Tissue Engineering Techniques

Bermueller, Christian; Schwarz, Silke; Elsaesser, Alexander F.; Sewing, Judith; Baur, Nina; Bomhard, Achim von; Scheithauer, Marc O.; Notbohm, Holger; Rotter, Nicole

doi:10.1089/ten.tea.2012.0650

Cited by 64 publications

(45 citation statements)

References 72 publications

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“…The nasal septum is potentially a simpler biopsy procedure with a lower risk of donor site morbidity. In addition, chondrocytes extracted from the nasal septum have been broadly studied in tissue engineering for their capacity to produce a hyaline cartilage matrix [24,[27][28][29] and have been used clinically for repair of septal defects [17]. Only one detailed in vivo study to date has considered the use of nasal chondrocytes for tissue engineering a hypertrophic cartilage template for bone regeneration [30].…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Repair of bone defects in vivo using tissue engineered hypertrophic cartilage grafts produced from nasal chondrocytes

et al. 2017

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The regeneration of large bone defects remains clinically challenging. The aim of our study was to use a rat model to use nasal chondrocytes to engineer a hypertrophic cartilage tissue which could be remodelled into bone in vivo by endochondral ossification.Primary adult rat nasal chondrocytes were isolated from the nasal septum, the cell numbers expanded in monolayer culture and the cells cultured in vitro on polyglycolic acid scaffolds in chondrogenic medium for culture periods of 5-10 weeks. Hypertrophic differentiation was assessed by determining the temporal expression of key marker genes and proteins involved in hypertrophic cartilage formation. The temporal changes in the genes measured reflected the temporal changes observed in the growth plate. Collagen II gene expression increased 6fold by day 7 and was then significantly downregulated from day 14 onwards. Conversely, collagen X gene expression was detectable by day 14 and increased 100-fold by day 35. The temporal increase in collagen X expression was mirrored by increases in alkaline phosphatase gene expression which also was detectable by day 14 with a 30-fold increase in gene expression by day 35. Histological and immunohistochemical analysis of the engineered constructs showed increased chondrocyte cell volume (31-45 µm), deposition of collagen X in the extracellular matrix and expression of alkaline phosphatase activity. However, no cartilage mineralisation was observed in in vitro culture of up to 10 weeks. On subcutaneous implantation of the hypertrophic engineered constructs, the grafts became vascularised, cartilage mineralisation occurred and loss of the proteoglycan in the matrix was observed.Implantation of the hypertrophic engineered constructs into a rat cranial defect resulted in angiogenesis, mineralisation and remodelling of the cartilage tissue into bone. Micro-CT analysis indicated that defects which received the engineered hypertrophic constructs showed 38.48% in bone volume compared to 7.01% in the control defects. M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 4Development of tissue engineered hypertrophic cartilage to use as a bone graft substitute is exciting development in regenerative medicine. This is a proof of principal study demonstrating the potential of nasal chondrocytes to engineer hypertrophic cartilage which will remodel into bone on in vivo transplantation. This approach to making engineered hypertrophic cartilage grafts could form the basis of a new potential future clinical treatment for maxillofacial reconstruction.

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Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Repair of bone defects in vivo using tissue engineered hypertrophic cartilage grafts produced from nasal chondrocytes

et al. 2017

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“…32 Briefly, the skin of the nasal dorsum of male Lewis rats (weight: 300-350 g) was incised under sterile conditions. The nasal septum was accessed from above while positioning the nasal bones anteriorly.…”

Section: Animal Modelmentioning

confidence: 99%

“…Nine animals per time point were estimated to be sufficient for statistical evaluation. The number of animals was determined according to our previously published work 32 and comparable animal studies with rats. [33][34][35] Twenty-seven animals received seeded (group 1) and 27 animals received unseeded pNSC (group 2) scaffolds.…”

Section: Experimental Groupsmentioning

confidence: 99%

“…31 The first application of tissue-engineered cartilage in an orthotopic rat model of nasal septum cartilage repair has just been published recently by our group. 32 In the present study, we modified this animal model to test xenogeneic decellularized cartilage scaffolds in vivo focusing on biocompatibility, immunological reactions, and prevention of septal perforations after artificial cartilage trauma. By combining nasal chondrocytes with pNSC, we aimed to develop a novel clinically applicable strategy for the reconstruction of nasal cartilage.…”

Section: Introductionmentioning

confidence: 99%

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In VitroCytotoxicity andIn VivoEffects of a Decellularized Xenogeneic Collagen Scaffold in Nasal Cartilage Repair

Elsaesser¹,

Bermueller²,

Schwarz³

et al. 2014

Tissue Engineering Part A

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Tissue engineering is considered a promising future option for nasal cartilage repair. However, until now, an optimal material has not been identified for this specific purpose. Therefore, the aim of this study was to analyze a recently developed decellularized collagen matrix, which has promising material properties for septal cartilage repair. A tetrazolium dye based cytotoxicity assay using rat nasal septum chondrocytes was performed to examine the cytotoxic effects of decellularized cartilage matrices. Unseeded scaffolds as well as scaffolds seeded with chondrocytes were implanted in nasal septum defects in Lewis rats to investigate the cellular and humoral inflammatory responses in the surrounding tissue as well as the effect on the formation of nasal septum perforations. Samples were analyzed histochemically and immunohistochemically after 1, 4, and 12 weeks. Although cells for the cytotoxicity assay were cultured under serum-free conditions for 24 h to increase sensitivity, no cytotoxic effects were detected. Histological and immunohistochemical evidence displayed that the implanted scaffolds induced minor macrophage and lymphocyte infiltration and were well integrated at the contact site to native cartilage and between the mucosal membranes. The biocompatibility index revealed only slightly irritating effects during the study period. Septal perforations were prevented efficiently. In summary, our results provide evidence that decellularized xenogeneic collagen scaffolds are suitable for cartilage tissue engineering. The scaffolds were integrated well into septal cartilage defects without causing a strong inflammatory reaction and prevented the development of nasal septum perforations. Therefore, we envision the possibility to use them in nasal cartilage repair in the future.

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“…[1][2][3][4][5] In recent years, considerable attention has been given to biodegradable synthetic polymers and their application in cartilage tissue engineering. 6,7 Scaffolds seeded with chondrocytes or stem cells have been widely investigated for use in the tissue engineering of cartilage.…”

Section: Introductionmentioning

confidence: 99%

Electrospun gelatin/polycaprolactone nanofibrous membranes combined with a coculture of bone marrow stromal cells and chondrocytes for cartilage engineering

Feng

Huang

et al. 2015

IJN

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Electrospinning has recently received considerable attention, showing notable potential as a novel method of scaffold fabrication for cartilage engineering. The aim of this study was to use a coculture strategy of chondrocytes combined with electrospun gelatin/polycaprolactone (GT/PCL) membranes, instead of pure chondrocytes, to evaluate the formation of cartilaginous tissue. We prepared the GT/PCL membranes, seeded bone marrow stromal cell (BMSC)/chondrocyte cocultures (75% BMSCs and 25% chondrocytes) in a sandwich model in vitro, and then implanted the constructs subcutaneously into nude mice for 12 weeks. Gross observation, histological and immunohistological evaluation, glycosaminoglycan analyses, Young’s modulus measurement, and immunofluorescence staining were performed postimplantation. We found that the coculture group formed mature cartilage-like tissue, with no statistically significant difference from the chondrocyte group, and labeled BMSCs could differentiate into chondrocyte-like cells under the chondrogenic niche of chondrocytes. This entire strategy indicates that GT/PCL membranes are also a suitable scaffold for stem cell-based cartilage engineering and may provide a potentially clinically feasible approach for cartilage repairs.

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Marine Collagen Scaffolds for Nasal Cartilage Repair: Prevention of Nasal Septal Perforations in a New Orthotopic Rat Model Using Tissue Engineering Techniques

Cited by 64 publications

References 72 publications

Repair of bone defects in vivo using tissue engineered hypertrophic cartilage grafts produced from nasal chondrocytes

Repair of bone defects in vivo using tissue engineered hypertrophic cartilage grafts produced from nasal chondrocytes

In VitroCytotoxicity andIn VivoEffects of a Decellularized Xenogeneic Collagen Scaffold in Nasal Cartilage Repair

Electrospun gelatin/polycaprolactone nanofibrous membranes combined with a coculture of bone marrow stromal cells and chondrocytes for cartilage engineering

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