Sustained‐release microcapsules of a bone formation stimulant, TAK‐778, for local injection into a fracture site

Background. To find a better prophylactic regimen, the pathogenesis of acquired heterotopic ossification (AHO) must be more understood. To date, AHO formation is largely thought to be related to inflammation, which is activated by trauma, resulting in AHO by up-regulation of pro-osteogenic genes. Methods. Brain-traumatic/burn/tenotomy model is firstly used in experiment. At first, 44 rats were randomly divided into two groups: E group and C group. Two rats in every group were euthanized during second, third, fourth, sixth, eighth, tenth weeks for collecting tendon. The remaining rats survived until tenth week for X-Ray radiation examination to confirm the size of AHO.Then, 124 rats were randomly divided into four group: P group, L group, M group, H group. The three rats of every group were euthanized during every week of the first seven weeks for collecting tendon to detect P65 protein. The remaining rats survived until tenth week for X-Ray examination to confirm the size of AHO. Results. The success rate of Brain-traumatic/Burn/Tenotomy model is 100%. Difference of P65 expression in E group and in C group are statistically significant,and that in E group is higher.Pharmacologic inhibition of Nf-ҝb signaling pathway limits AHO formation, and that The bone formation content of M group is decreased. Conclusion. Brain-traumatic/Burn/Tenotomy model is highly reliable.Results indicate that the Nf-ҝb /p65 signaling response occurs in the forming process of AHO. PDTC limits formation of AHO. The most effective concentration is 6mg/ml for local injection.

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Inhibition of Nf-ҝb prevents trauma-induced heterotopic ossification in rat model

10.7287/peerj.preprints.2709v1 ◽

2017 ◽

Author(s):

Jinyong Ju ◽

Du Yu ◽

Feng Xue ◽

Yong Zhao ◽

Weizhe Shi ◽

...

Keyword(s):

Bone Formation ◽

Heterotopic Ossification ◽

Success Rate ◽

Signaling Pathway ◽

Rat Model ◽

Effective Concentration ◽

Local Injection ◽

Forming Process ◽

Prophylactic Regimen ◽

X Ray

Background. To find a better prophylactic regimen, the pathogenesis of acquired heterotopic ossification (AHO) must be more understood. To date, AHO formation is largely thought to be related to inflammation, which is activated by trauma, resulting in AHO by up-regulation of pro-osteogenic genes. Methods. Brain-traumatic/burn/tenotomy model is firstly used in experiment. At first, 44 rats were randomly divided into two groups: E group and C group. Two rats in every group were euthanized during second, third, fourth, sixth, eighth, tenth weeks for collecting tendon. The remaining rats survived until tenth week for X-Ray radiation examination to confirm the size of AHO.Then, 124 rats were randomly divided into four group: P group, L group, M group, H group. The three rats of every group were euthanized during every week of the first seven weeks for collecting tendon to detect P65 protein. The remaining rats survived until tenth week for X-Ray examination to confirm the size of AHO. Results. The success rate of Brain-traumatic/Burn/Tenotomy model is 100%. Difference of P65 expression in E group and in C group are statistically significant,and that in E group is higher.Pharmacologic inhibition of Nf-ҝb signaling pathway limits AHO formation, and that The bone formation content of M group is decreased. Conclusion. Brain-traumatic/Burn/Tenotomy model is highly reliable.Results indicate that the Nf-ҝb /p65 signaling response occurs in the forming process of AHO. PDTC limits formation of AHO. The most effective concentration is 6mg/ml for local injection.

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Releasing Behavior of Lipopolysaccharide from Gelatin Modulates Inflammation, Cellular Senescence, and Bone Formation in Critical-Sized Bone Defects in Rat Calvaria

Materials ◽

10.3390/ma13010095 ◽

2019 ◽

Vol 13 (1) ◽

pp. 95 ◽

Cited By ~ 3

Author(s):

Jianxin Zhao ◽

Yoshitomo Honda ◽

Tomonari Tanaka ◽

Yoshiya Hashimoto ◽

Naoyuki Matsumoto

Keyword(s):

Bone Formation ◽

Sustained Release ◽

Cellular Senescence ◽

Bone Defects ◽

Gelatin Sponge ◽

Inflammatory Reactions ◽

Rat Calvaria ◽

Cox 2 ◽

Vacuum Heating

Lipopolysaccharide (LPS) is a well-known strong inducer of inflammation. However, there is little information regarding how LPS-release behavior affects cellular senescence at the affected area. In this paper, we demonstrate that a vacuum-heating technique (dehydrothermal treatment) can be utilized to prepare an LPS sustained-release gelatin sponge (LS-G). LPS sustained release from gelatin leads to the long-term existence of senescent cells in critical-sized bone defects in rat calvaria. Three types of gelatin sponges were prepared in this study: a medical-grade gelatin sponge with extremely low LPS levels (MG), LS-G, and a LPS rapid-release gelatin sponge (LR-G). Histological (H-E) and immunohistochemical (COX-2, p16, and p21) staining were utilized to evaluate inflammatory reactions and cellular senescence one to three weeks after surgery. Soft X-ray imaging was utilized to estimate new bone formation in the defects. The LR-G led to stronger swelling and COX-2 expression in defects compared to the MG and LS-G at 1 week. Despite a small inflammatory reaction, LS-G implantation led to the long-term existence of senescent cells and hampered bone formation compared to the MG and LR-G. These results suggest that vacuum heating is a viable technique for preparing different types of materials for releasing bacterial components, which is helpful for developing disease models for elucidating cellular senescence and bone regeneration.

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