Development of Bone Adhesive Materials based on Collagen-mimetic Peptides and Carbene-mediated Diazirine Crosslinkers
by Thien Duc Huu Pham
Date of Examination:2024-02-07
Date of issue:2024-08-22
Advisor:Prof. Dr. Johannes C. L. Walker
Referee:Prof. Dr. Johannes C. L. Walker
Referee:Prof. Dr. Andreas Janshoff
Referee:Prof. Dr Arndt Schilling
Persistent Address:
http://dx.doi.org/10.53846/goediss-10688
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Abstract
English
Traditional mechanical fixation methods such as screws, support plates, staples, and sutures remain predominant in treating bone trauma. However, these methods can cause localized tissue damage, leading to infection and other complications. Medical adhesives offer an advantageous alternative through minimally invasive procedures that bond materials quickly and easily without external fixatives. Suitable bone adhesives, especially for fragment and comminuted fractures, could improve the efficiency of patient care.[1] Bone is a complex tissue composed predominantly of inorganic calcium phosphate and organic collagen. It is dynamic, constantly remodelling and regenerating to maintain its functions. Bone cells, including osteoblasts, osteoclasts, and osteocytes, work together to rebuild and regenerate bone, especially after injuries such as fractures.[2][3] Bone stability during the regeneration phase is critical. While simple fractures can be externally supported with plaster casts, complex fractures often require surgical fixation with screws, rods, nails, and plates. However, these methods can cause additional localized tissue damage, leading to infection and complications. In addition, smaller fragments, especially in osteoporotic bone, pose significant challenges to traditional fixation methods.[4] The development of medical adhesives offers a viable alternative to conventional treatment methods. These substances, applied to the fracture site, could effectively reattach even small bone fragments. Existing medical adhesives such as NeoOrtho© and Histoacryl©, which are primarily based on methacrylates and cyanoacrylates, are unsuitable for bone bonding due to potential toxicity that inhibits natural bone formation.[4] Recent materials such as Tetranite® and Kryptonite© show promise for bone fragment fixation, but achieving a balance between mechanical properties and biodegradability remains a challenging objective.[1] The aim of this work is to investigate synthetic bone adhesive materials based on collagen-mimetic peptides (CMPs) in combination with carbene-mediated diazirine crosslinkers for photochemical cross-linking. The primary objective is to develop a biomimetic adhesive that can be photochemically cross-linked to effectively stabilise fracture sites. The collagen-like structure of these materials, which exhibit high affinity to bone tissue and biodegradability, offers significant advantages over metal implants. These include the absence of secondary procedures, ease of application, shorter operating times, fewer complications, less additional tissue damage and accessibility to difficult sites.[4][5] The challenges of this project are to apply the synthesis methods for peptides established in the working group to different motifs of collagen-mimetic peptides and to modify them with regard to stability and cross-linking properties. Suitable diazirine molecules must be synthesised for the cross-linking reactions, and collagen-mimetic peptides could be functionalised with various diazirine building blocks. It is proposed that carbene-mediated cross-linking will significantly improve the mechanical properties of CMPs, making them suitable for clinical application in bone healing. [1] H. B. Bingol, J. C. Bender, J. A. Opsteen, S. C. G. Leeuwenburgh, Mater. Today Bio 2023, 19, 100599. [2] A. F. Schilling, W. Linhart, S. Filke, M. Gebauer, T. Schinke, J. M. Rueger, M. Amling, Biomaterials 2004, 25, 3963–3972. [3] U. Welsch, W. Kummer, T. Deller (Eds.) Histologie. Zytologie, Histologie und mikroskopische Anatomie: das Lehrbuch, Elsevier Urban & Fischer, München, 2018. [4] K. O. Böker, K. Richter, K. Jäckle, S. Taheri, I. Grunwald, K. Borcherding, J. von Byern, A. Hartwig, B. Wildemann, A. F. Schilling et al., Materials 2019, 12, 3975. [5] D. Cao, J. Ding, Regenerative biomaterials 2022, 9, rbac098.
Keywords: Collagen; Collagen-memetic peptides; Solid-phase peptide synthesis; Cross-link
