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Friday, January 27, 2023

Regenerative Drug Restores Bone In Preclinical Study

Mouse jawbone degeneration following ligation followed by jawbone regeneration after ligation and after drug administration. (Aab) Ligation-induced periodontitis model. Use Dumont forceps to pass a 5-0 silk suture through the interdental space between the maxillary first, second, and third molars. As shown in the cartoon (a) and photomicrograph (b), suture securely using a three-knot and trim excess suture using spring scissors. Taken from ref. (31). (Ba–c) Micro-CT scans of mouse jaws during the 10-day ligation on days 0, 5, and 10. Control images represent the group that will not receive the drug (n = 3) (control, upper row) and experimental group images represent the group that will receive the drug (n = 3) (experimental, lower row). The red arrow shows the left maxillary second molar with bony degeneration extending to the adjacent first and third molars. Image inverted 180 degrees for visual clarity (now: top of mandible, bottom of maxilla). (C) On days 5 and 10 after ligation placement, degenerated areas were identified for all animals tested and shown. The y-axis is: area of ​​bone loss (mm2); (n = 7); error bars represent standard error; for days 0-5, p = 0.00289; for days 0-10, p = 7.33084 × 10−11; for Days 5-10, p = 3.60818 × 10-7. (**) indicates p less than 0.01. In (D) the area of ​​bone growth can be seen after ligation but without drug administration (no drug control) versus drug-administered mice (DPCA-PEG). Mice were injected subcutaneously with DPCA-PEG on days 0 and 8 after ligature placement and removal. MicroCT scans were acquired on day 15 (day 5 post ligation) and day 30 (day 20 post ligation) of the experiment. Here, a statistical analysis of bone growth area (mm2) can be seen. At day 15 (blue bar) (n = 12), there was a significant difference between drug-free control mice (n = 10) and DPCA-PEG-treated mice (p = 0.00253). The same was true at day 30, where DPCA-PEG-treated mice showed a highly significant difference (p = 0.00612) from the drug-free control group (red bar). Area analysis was performed as described in Materials and methods. Y-axis = bone regeneration area (mm2); error bars represent standard errors; p values ​​are expressed as = p less than 0.05; (**) = p less than 0.01. Mouse jaws analyzed n = 10 for ligation, no drug; n = 12 for ligation/medication. In (E) micro-CT data, a representative mouse maxilla with the ligature removed at day 10, scanned at day 10, and then at day 30 compared to a representative mouse maxilla undergoing ligation and DPCA Rescan (Ea,b) of PEG drugs seen on day 10 and day 30 (Ec,d). Regeneration levels in the drug-treated group showed almost, if not complete, recovery to pre-experiment levels (da0) (Ed,e). In (F), there was no change in bone histology after approximately 6 months. Mice injected with the DPCA-PEG drug were kept for additional observation as they aged. Mice were rescanned six months after the da 30 scan (upper panel) and compared to the day 30 scan by overlaying the two scans on da 30 and da 220 (lower panel). The black lines are da 30 scans and the red lines are da 220 scans. Although shown as two lines, they happen to overlap. The results are representative of three mice. Credit: Frontiers in Dental Medicine

(2022). DOI: 10.3389/fdmed.2022.992722

Bone loss is a part of aging that affects the quality of life and mobility of many older adults, yet there are limited regenerative therapies to improve their health and well-being. Now, a study led by Lankenau Institute of Medical Research (LIMR) scientist Ellen Heber-Katz, Ph.D., has demonstrated that an experimental regenerative medicine developed in her lab can restore bone in animals. This Preclinical studies Focus on the periodontal disease model, which causes the gums and bone loss cause tooth loss. In older adults, the disease not only causes pain and discomfort, but is the most common cause of tooth loss, affecting 30-60% of adults.However, the findings suggest that the experimental time-releasedrug , known as 1,4-DPCA, completely repairs diseased gums and the surrounding jawbone, completely preventing tooth loss.Findings were published in November by the Heber-Katz team at LIMR, part of Main Line HealthFrontiers in Dental Medicine

. “The development of this experimental drug represents one of the most cutting-edge research directions LIMR is driving in the 21st century,” said Institute President and CEO George Prendergast. “Beyond the uncertainty surrounding stem cell therapy, this study provides the first preclinical proof of concept for an off-the-shelf drug that can significantly improve an individual’s healthspan by regenerating bone. It also presents for the first time this Potential Antiaging Uses medical treatement on how to broaden how to use it to guide the perfect recover

by the body. ” Periodontal treatment is a branch of Heber-Katz researchregenerative medicine

, she took a startling new direction in the mid-1990s. That’s when she discovered a laboratory mouse strain that disproved the scientific assumption that only amphibians such as starfish and salamanders can heal wounds in a way that it appears the injury never occurred. “The results of this study were as robust as we expected,” said Heber-Katz, the Daniel B. and Florence E. Green Research Chair in Regenerative Medicine. “The repair of a lot of lost bone and tissue has been done. I’m optimistic that this drug will move forward and eventually be used in prophylaxis tooth loss in patients withperiodontal disease

— one of the many ways we think it might be useful. ”

The drug 1,4-DPCA works by inhibiting a molecule that prevents the production of a master molecule called hypoxia-inducible factor-1 (HIF-1a), a key component of the body’s healing response. By temporarily elevating HIF-1a, the drug shifts the metabolic state of the tissue to one for early fetal development, in this case allowing for perfect healing without scarring. Heber-Katz came to LIMR, an organization with expertise in early drug discovery and development, to advance research on compounds such as 1,4-DPCA to activate HIF-1a.The works are based on her earlier biological research

On how tissue regeneration is stimulated during the body’s healing response to injury.

Heber-Katz’s colleagues include LIMR faculty members Azamat Aslanukov, MD, and Kamila Bedelbaeva, MD. Additional collaborating researchers are from the Penn School of Dental Medicine and the University of California, Berkeley.

  • Heber-Katz has two related patent-pending products nearing human testing: Topical or injectable hydrogel medications made from 1,4-DPCA or related compounds. These formulations are used to promote skin healing or restore skin integrity, including tissue damaged by natural aging.chronic wounds that don’t usually heal
  • the elderly

1,4-DPCA-infused sutures prevent scarring during surgical wound healing
More information: Elan Zebrowitz et al., Prolyl hydroxylase inhibitors induce alveolar bone and soft tissue regeneration in a mouse model of periodontitis through metabolic reprogramming, Frontiers in Dental Medicine (2022).

DOI: 10.3389/fdmed.2022.992722
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Regenerative medicine restores bone in preclinical study (2023, January 19)
Retrieved January 19, 2023

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