Rabbit defect model

AI2O3 and Zr02 are considered to be nonbioactive ceramics and are frequently used as the articular heads of total arthroplasties such as total hip prostheses, total shoulder prostheses, and maxillar articular replacements. No unwanted biological effects could be observed in vivo, and no cytotoxic effects have been evidenced in vitro for both compounds except for some formation of granuloma around wear particles of these materials. Oonishi et al. (1997) have also shown small amounts of new bone formation between AI2O3 particles in an experimental rabbit femoral defect model. 

Lin K, et al. Degradation and silicon excretion of the calcium silicate bioactive ceramics during bone regeneration using rabbit femur defect model. J Mater Sci Mater Med 2015 26(6) 197. 

Ren et al. further demonstrated the osteogenic capabilities of cultured MSCs in PLGA/NHA composites scaffold using a rabbit mandibular defect model [96]. 

As an example, the appropriate sequence of studies for the development of a new biodegradable bone regeneration material might be (1) biomaterial synthesis and structural characterization (2) scaffold fabrication and measurements of mechanical and degradation properties in vitro (3) biocompatibihty and bone formation assessed by cell culture in vitro (4) biocompatibihty and degradation of the material in vivo, typically by subcutaneous implantation in a lower-level animal model such as a rat, (5) if no significant toxic effect is observed, the material is then evaluated for its intended appKcation such as an appropriate bone defect model in a higher-level animal such as a rabbit (6) if the material functions well... 

Common long bone defect models include the rabbit radial model (most popular), rat femoral model, and the dog radial model. A composite bone scaffold consisting of nano-hydroxyapatite, collagen, and PLA was found to integrate the rabbit radial defect after 12 weeks [49]. The effect of bone morphogenetic protein was evaluated in the rat femoral defect model [4]. It should be noted that the rat model requires either internal or external fixation. In the dog model, ulnae fractures may occur, resulting in unexpected loss. 

Due to the regenerative capability of bone defects, it is typical in tissue engineering research to consider critical sized defects. The critical size of the defect (CSD), defined as the smallest size that does not heal by itself if left untreated over a certain period of time, is 15 mm in diameter for adult New Zealand white rabbit calvarial defect model. The rat calvarial model is also popular with a CSD of 8 mm in diameter. A bone biomimetic device consisting of a porous biodegradable scaffold of poly(DL-lactide) and type I collagen, human osteoblast precursor cells, and rhBMP-2 was shown to promote bone regeneration in this... 

Commonly used cartilage defect models include partial-thickness (chondral) and fuU-thickness (osteochondral) defects in rabbits and dogs [52]. The rabbit distal femoral defect model is a well-established, reproducible model. Creating a partial-thickness defect can be challenging because the cartilage thickness in the rabbit femoral condyles is only 0.25 to 0.75 mm (compared to 2.2 to 2.4 mm in humans) [53]. The dog distal femur defect model, by contrast, offers a larger defect size with which to work. Besides species, the age of the animal is also an important consideration since the potential for cartilage repair as well as the response to various treatments varies with different animals [53]. Skeletal maturity of the commonly used New Zealand white rabbits typically occurs between 4 and 6 months. 

Preclinical Studies Rabbit Trephine Defect Model... 

Kim J, McBride S, TeUis B, Alvarez-Urena P, Song Y-H, Dean DD, et al. Rapid-prototyped PLGA/ 3-TCP/hydroxyapatite nanocomposite scaffolds in a rabbit femoral defect model. Biofabrication 2012 4(2). [online]. 

The work by Spicer et al. (2013) investigated the use of porous polymethylmethacrylate/poly(DL-lactic-co-gtycolic acid)/ GL/colistin constructs as antibiotic-releasing hydrogel in a rabbit infected composite tissue defect model. The results indicate that the local delivery did not result in systemic side-effects (e.g., nephrotoxicity), and that the prolonged delivery of antibiotics may mitigate the failure of surgical implants placed in contaminated wounds. 

Silk fibroin-based scaffolds, like fibroin/PCL nano/microfibrous composite, were fabricated by the hybrid electrospinning method and showed improved properties in comparison with PCL microfibrous scaffolds, providing a suitable environment for MSC proliferation, adhesion, and differentiation into osteoblasts, in vitro. Moreover, in a rabbit calvarial defect model this material promoted new bone formation (Kwak et al., 2015). Silk fibroin membranes are an alternative to the widely used coUagen membranes, once similar volumes of bone regeneration were observed with the advantage of lower cost and zero risk of infection (Kim et al., 2014). 

HA has been used, both in soluble and crosslinked forms, as a carrier for calcium phosphate particles to stimulate bone regeneration. In a subcutaneous implantation model, an injectable paste-like material, consisting of beta-tricalcium phosphate (P-TCP), methylcellulose, and HA, increased the half-life of the P-TCP particles and ultimately vascularisation of the implantation bed [99]. In a unilateral tibial defect model in rabbits, the same formulation promoted a significant increase in new bone volume fraction after one week however, by 4 weeks, there was no difference in bone formation compared to controls [100]. Similarly, medical grade HA of three different MW (900,000 - Artz 1,900,000 - Suvenyl and 6,000,000 - Synvisc) were evaluated as carriers for octacalcium phosphate granules in a mouse subperiosteal calvarial model [101]. The formulations with... 

Bone defects surgically produced in sheep and rabbit models, have been treated with freeze dried methylpyrrohdinone chitosan [334-336]. hi view of improving bone tissue reconstitution with chitosan associated with calcium phosphate. Microscopic and histological analyses showed the presence of an osteogenic reaction moving from the rim of the surgical lesion toward the center. In control lesions, dense fibrous tissue, without the characteristic histoarchitecture of bone was observed. 

Four classes of LDL receptor mutations have been identified. Class 1 mutations are characterized by the failure of expression of the receptor protein. It is possible, however, that a modified protein is produced but it is not recognized as an LDL receptor protein. Class 2 mutations involve a nonsense mutation (premature termination of protein synthesis Chap. 17), and result in a defect in the transfer of the receptor from the endoplasmic reticulum to the cell membranes. This class of mutation is common in Afrikaners and Lebanese. The Watanabe heritable hyperlipidemic rabbit (WHHL) is an animal model which has a Class 2 defect and has been used extensively for the study of familial hypercholesterolemia. Class 3 mutations result in abnormal binding of LDL. This can be caused by alterations in the amino acid sequence of Domain 1. Class 4 mutations are those with defective internalization due to the receptor s inability to be located in coated pits. This is the result of mutations in the fifth, C-terminal domain. 

The teratogenic syndrome of in utero VPA exposure in humans includes neural, craniofacial, cardiovascular, and skeletal defects. A similar teratology is exhibited in rodents, rabbits, and nonhuman primates. The most dramatic of malformations associated with gestational VPA exposure is spina bifida, a neural tube defect that is estimated to occur in 1-2% of VPA exposed infants. Mice are the only known animal model to exhibit a comparable effect of VPA on neural tube development. 

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