Stereocomplexation of Poly(l-lactide) and Random Copolymer Poly(d-lactide-<i>co</i>-ε-caprolactone) To Enhance Melt Stability

Stereocomplexation of Poly(l-lactide) and Random Copolymer Poly(d-lactide-<i>co</i>-ε-caprolactone) To Enhance Melt Stabilit

Development and characterization of various osteoarthritis models for tissue engineering

<div><p>Osteoarthritis (OA) is characterized by a progressive loss of articular cartilage, subchondral bone sclerosis and synovial inflammation and is the most common chronic condition worldwide today. However, most treatments have focused on pain relief and OA symptoms. For these reasons, many ongoing studies are currently trying to develop efficient and successful therapies based on its pathology. Animal models that mimic the histopathology and symptoms of OA have a critical role in OA research and make it possible to investigate both secondary osteoarthritic changes due to a precedent event such as traumatic injury and naturally occurring changes for the development of therapeutics which can be tested in preclinical and clinical OA trials. We induced OA in various animal models including rats, rabbits and guinea pigs by chemical, surgical and naturally occurring methods. In particular, the Dunkin-Hartley guinea pig is very attractive as an OA animal model because OA slowly progresses which is similar to human primary OA. Thus, this animal model mimics the pathophysiological process and environment of human primary OA. Besides the spontaneous OA model, anterior cruciate ligament transection (ACLT) with medial meniscectomy and bilateral ovariectomy (OVX) as well as a chemical technique using sodium monoiodoacetate (MIA) were used to induce OA. We found that ACLT in the rat model induced OA changes in the histology and micro-CT image compared to OVX. The osteoarthritic change significantly increased following ACLT surgery in the rabbit model. Furthermore, we identified that OA pathogenic changes occurred in a time-dependent manner in spontaneous Dunkin-Hartley guinea pigs. The MIA injection model is a rapid and minimally invasive method for inducing OA in animal models, whereas the spontaneous OA model has a slow and gradual progression of OA similar to human primary OA. We observed that histological OA change was extraordinarily increased at 9 ½ months in the spontaneous OA model, and thus, the grade was similar with that of the MIA model. Therefore, this study reports on OA pathology using various animal models as well as the spontaneous results naturally occurring in an OA animal model which had developed cartilage lesions and progressive osteoarthritic changes.</p></div

Histological studies of OA knee joints induced by surgical induction techniques.

<p>(A-C) Macroscopic images of hematoxylin and eosin staining of the rat animal model. (D-F) Macroscopic images of safranin O staining of the rat animal model. (G, H) Macroscopic images of hematoxylin and eosin staining of the rabbit animal model. (I, J) Macroscopic images of alcian blue staining of the rabbit animal model. (Scale bars: 200 μm).</p

Micro-computed tomography (micro-CT) images of the knee joints from the OA animal models.

<p><b>The micro-CT images were reconstructed to three-dimensional images.</b> (A-C) Images of the knee joints from the OA rat model induced by anterior cruciate ligament transection and bilateral ovariectomy. (D-E) Images of the knee joints from the OA rabbit model induced by anterior cruciate ligament transection. (F-K) Micro-CT images of the Dunkin-Hartley guinea pig OA knee joints. (G) Image of OA knee joints induced by sodium monoiodoacetate (MIA) chemical injection. (H-K) Micro-CT images of Dunkin-Hartley guinea pig knee joints according to age in the spontaneous OA model.</p

OA induction procedures for anterior cruciate ligament transection (ACLT) in the animal models.

<p>(A-D) The ACLT images for the rat animal model. (A) A vertical midline incision was made in the skin, followed by the elimination of the fat pad, and then, the anterior cruciate ligament (ACL) was exposed in the knee joint. (B) The ACL was dissected with a surgical scissor. (C) The medial meniscus was completely removed, and the medial collateral ligament (MCL) was transected too. (D) The image shows the extracted medial meniscus from the knee joint of rats. (E-H) The ACLT images for the rabbit animal model. (E) After a vertical midline incision, the patella was pushed laterally to expose the ACL. (F) The exposed ACL was cut in the rabbit model. (G) The medial meniscus was removed, and the MCL was transected without injury to the cartilage. (H) The image shows the completely extracted medial meniscus from the rabbit knee joint.</p

Evaluation of the modified Mankin score according to the cartilage structure, chondrocyte pathology, glycosaminoglycan contents and tidemark integrity in the OA rabbit model.

<p>The total global score was the sum of these four scores (*<i>P</i> < 0.05).</p

Evaluation of the modified Mankin score according to cartilage structure, chondrocyte pathology, glycosaminoglycan contents and tidemark integrity in the OA rat model.

<p>The total global score was the sum of these four scores (*<i>P</i> < 0.05).</p

Evaluation of the modified Mankin score according to the cartilage structure, chondrocyte pathology, glycosaminoglycan contents and tidemark integrity in the OA Dunkin-Hartley guinea pig model.

<p>The total global score was the sum of these four scores (*<i>P</i> < 0.05).</p

Images for the surgical and chemical induction procedures for the OA animal models.

<p>(A-C) Images of the bilateral ovariectomy (OVX) procedure in the rat animal model. (A) The ovary was exposed which is located in the tip of the uterine horn. (B) The ovarian duct was ligated at 1 cm distal to the ovary with a suture. (C) The ligated ovarian duct was cut and extracted by a surgical scissor. (D) To induce OA, sodium monoiodoacetate (MIA) was injected into the knee joint of a Dunkin-Hartley guinea pig.</p

Histological studies of OA knee joints in Dunkin-Hartley guinea pigs.

<p>Hematoxylin and eosin staining (upper line) and alcian blue staining (lower line) of the retrieved knee joints from guinea pigs. (B, H) The stained image of OA knee joints induced by sodium monoiodoacetate (MIA) chemical injection. (C-F, I-L) The stained images of Dunkin-Hartley guinea pig knee joints according to age in the spontaneous OA model. (Scale bars: 100 μm).</p