A new in vivo model for testing cartilage grafts and biomaterials: the 'rabbit pinna punch-hole' model

Koppel, Paul; Osch, Gerjo J.V.M. van; Verwoerd, C. D. A.; Verwoerd-Verhoef, H.L.

doi:10.1016/s0142-9612(00)00298-2

Cited by 30 publications

(24 citation statements)

References 31 publications

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“…4 Examples of mammalian epimorphic regeneration include the regrowth of antlers of deer 5 and moose 3 and punched ear hole closure in rabbits. 6 Among these examples is the MRL mouse, first identified in 1996 as a mouse model of regeneration, which exhibits closure of punched ear holes with the formation of a blastemalike structures. This results in the perfect extended to include S and G 2 checkpoints through the interaction with PCNA and 14-3-3σ, respectively.…”

Section: Epimorphic Regeneration In Mice Is P53-independentmentioning

confidence: 99%

Epimorphic regeneration in mice is p53-independent

Arthur¹,

Demarest²,

Clark³

et al. 2010

Cell Cycle

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T he process of regeneration is most readily studied in species of sponge, hydra, planarian and salamander (i.e., newt and axolotl). The closure of MRL mouse ear pinna through-and-through holes provides a mammalian model of unusual wound healing/regeneration in which a blastema-like structure closes the ear hole and cartilage and hair follicles are replaced. Recent studies, based on a broad level of DNA damage and a cell cycle pattern of G 2 /M "arrest," showed that p21Cip1/Waf1 was missing from the MRL mouse ear and that a p21-null mouse could close its ear holes. Given the p53/p21 axis of control of DNA damage, cell cycle arrest, apoptosis and senescence, we tested the role of p53 in the ear hole regenerative response. Using backcross mice, we found that loss of p53 in MRL mice did not show reduced healing. Furthermore, cross sections of MRL. p53 -/-mouse ears at 6 weeks post-injury showed an increased level of adipocytes and chondrocytes in the region of healing whereas MRL or p21 -/-mice showed chondrogenesis alone in this same region, though at later time points. In addition, we also investigated other cell cyclerelated mutant mice to determine how p21 was being regulated. We demonstrate that p16 and Gadd45 null mice show little healing capacity. Interestingly, a partial healing phenotype in mice with a dual Tgfβ/Rag2 knockout mutation was seen. These data demonstrate an independence of p53 signaling for mouse appendage regeneration and suggest that the role of p21 in this process is possibly through the abrogation of the Tgfβ/Smad pathway.

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Section: Epimorphic Regeneration In Mice Is P53-independentmentioning

confidence: 99%

Epimorphic regeneration in mice is p53-independent

Arthur¹,

Demarest²,

Clark³

et al. 2010

Cell Cycle

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“…10,14,19 Studies have shown that alginate stimulates the expression of the chondrogenic phenotype. The results of these studies have demonstrated that the chondrocytes can maintain their phenotype with embedded in alginate gels.…”

Section: Introductionmentioning

confidence: 99%

“…The results of these studies have demonstrated that the chondrocytes can maintain their phenotype with embedded in alginate gels. 10,14,19 Furthermore, a great advantage of alginate is that it can easily be dissolved by chelating substances, such as ethylenediaminetetraacetic acid (EDTA) or phosphates, increasing the range of applications. This work intends to develop a cultured system for expanding chondrocytes with recovery of the proliferated chondrocytes for further application of cartilage repairing and to overcome the shortage of autologous chondrocytes for direct reimplantation.…”

Section: Introductionmentioning

confidence: 99%

Chondrocytes culture in three‐dimensional porous alginate scaffolds enhanced cell proliferation, matrix synthesis and gene expression

Lin

Yen

et al. 2008

J Biomedical Materials Res

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For the limited availability of autologous chondrocytes, a cultured system for expansion in vitro until sufficient cells are obtained must be developed. These cells must maintain their chondrocyte phenotype in vitro as well as in vivo, following implantation to ensure that differentiated chondrocytes synthesize a normal hyaline cartilage matrix and not a fibro-cartilage matrix. This study uses porous three-dimensional (3-D) alginate scaffolds within a perfusion system to culture low-density (5 x 10(5) cells) primary porcine chondrocytes for 1-4 weeks to study their proliferation and differentiation. The results of RT-PCR reveal that most cells could maintain their differentiation state for up to 4 weeks of culturing. Chondrocytes proliferated to 3 x 10(7) cells after 4 weeks in culture. Alginate scaffolds induced the formation of chondrocyte clusters and stimulated the synthesis of matrix, which effects were evaluated using histology and electron microscopy. These findings demonstrate that culturing chondrocytes in alginate scaffolds may effectively prevent the dedifferentiation and improve autologous chondrocyte transplantation.

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“…Die Angst um eine Kontamination mit Prionen, die f ü r die BSE-Krankheit verantwortlich sind, hat den Einsatz von DBM in der Hals-, Nasen-, Ohrenheilkunde seitdem erheblich reduziert. Um die Durchf ü hrbarkeit neu entwickelter Knorpeltransplantate zu bewerten wurde von ten Koppel et al im Tiermodell ein sogenanntes " ausgestanztes Ohr " entwickelt[137] . Mehrere L ö -cher (gestanzt) im Ohr eines Kaninchens wurden mit verschiedenen Arten von Knorpeltransplantaten aufgef ü llt und nach 3 Wochen deren Qualit ä t, Quantit ä t und Integration anhand eines semi-quantitativen Beurteilungs-Systems bewertet.…”

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Rhinochirurgie bei Kindern: Entwicklungsphysiologische und chirurgische Aspekte der wachsenden Nase

Verwoerd

Verwoerd-Verhoef

2010

Laryngo-Rhino-Otol

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The anatomy of the nasal skeleton in newborns and adults are not alike. The complete cartilaginous framework of the neonatal nose becomes partly and gradually ossified during the years of growth and is more vulnerable to trauma in that period. Injury in the early youth may have large consequences for development of a nasal deformity which will increase during growth and reach its peak during and after the adolescent growth spurt. To understand more of the underlying problems of nasal malformations and their treatment (septoplasty) these items became the focus of multiple animal studies in the last 40 years. The effects of surgery on the nasal septum varied considerably, seemingly depending on which experimental animal was used. In review, however, it appeared that the very different techniques of surgery might be even more influential in this respect. Study of one of the larger series of experiments in young rabbits comprised skeletal measurements with statistical analysis and microscopic observations of the tissues. The behaviour of hyaline cartilage of the human nose appeared to be comparable to that of mammals. Cartilage, although resilient, can be easily fractured whereas its tendency to integrated healing is very low, even when the perichondrium has been saved. Also surgical procedures - like in septoplasty - may result in growth disturbances of the nasal skeleton like deviation or nasal spine. Loss of cartilage, as might occur after a septum abscess, is never completely restored despite some cartilage regeneration. In this article the many experimental studies are reviewed and compared. Still there remains a lack of real consensus in the literature concerning the developmental effects of rhinosurgry in children. Based on their observations in animals and a few clinical studies, mostly with small numbers of patients but with a long follow-up, the authors have compiled a list of guidelines to be considered before starting to perform surgery on the growing midface in children.

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A new in vivo model for testing cartilage grafts and biomaterials: the 'rabbit pinna punch-hole' model

Cited by 30 publications

References 31 publications

Epimorphic regeneration in mice is p53-independent

Epimorphic regeneration in mice is p53-independent

Chondrocytes culture in three‐dimensional porous alginate scaffolds enhanced cell proliferation, matrix synthesis and gene expression

Rhinochirurgie bei Kindern: Entwicklungsphysiologische und chirurgische Aspekte der wachsenden Nase

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