A novel computationally engineered collagenase reduces the force required for tooth extraction in an ex-situ porcine jaw model

Journal of Biological Engineering

Research

Orel Cohen¹  Daniel Z. Bar¹  Maayan Gal¹  Adi Cohen¹  Ran Tohar¹  Evgeny Weinberg²  Tamar Ansbacher³  Adi Arieli⁴  Shlomo Matalon⁴  Shifra Levartovsky⁴ 

[1] Department of Oral Biology, Goldschleger School of Dental Medicine, Faculty of Medicine, Tel Aviv University, 6997801, Tel Aviv, Israel;Department of Oral Biology, Goldschleger School of Dental Medicine, Faculty of Medicine, Tel Aviv University, 6997801, Tel Aviv, Israel;Department of Periodontology and Oral Implantology, Goldschleger School of Dental Medicine, Faculty of Medicine, Tel Aviv University, 6997801, Tel Aviv, Israel;Department of Oral Biology, Goldschleger School of Dental Medicine, Faculty of Medicine, Tel Aviv University, 6997801, Tel Aviv, Israel;Hadassah Academic College, 91010, Jerusalem, Israel;Department of Oral Rehabilitation, Goldschleger School of Dental Medicine, Faculty of Medicine, Tel Aviv University, 6997801, Tel Aviv, Israel;

关键词: Collagen;    Collagenase;    Protein engineering;    Tooth extraction;    Minimally invasive medicine;   

DOI  :  10.1186/s13036-023-00366-4

 received in 2023-05-07, accepted in 2023-07-05,  发布年份 2023

来源: Springer

【 摘 要 】

The currently employed tooth extraction methods in dentistry involve mechanical disruption of the periodontal ligament fibers, leading to inevitable trauma to the bundle bone comprising the socket walls. In our previous work, we have shown that a recombinantly expressed truncated version of clostridial collagenase G (ColG) purified from Escherichia coli efficiently reduced the force needed for tooth extraction in an ex-situ porcine jaw model, when injected into the periodontal ligament. Considering that enhanced thermostability often leads to higher enzymatic activity and to set the basis for additional rounds of optimization, we used a computational protein design approach to generate an enzyme to be more thermostable while conserving the key catalytic residues. This process generated a novel collagenase (ColG-variant) harboring sixteen mutations compared to ColG, with a nearly 4℃ increase in melting temperature. Herein, we explored the potential of ColG-variant to further decrease the physical effort required for tooth delivery using our established ex-situ porcine jaw model. An average reduction of 11% was recorded in the force applied to extract roots of mandibular split first and second premolar teeth treated with ColG-variant, relative to those treated with ColG. Our results show for the first time the potential of engineering enzyme properties for dental medicine and further contribute to minimally invasive tooth extraction.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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