Mechanoregulation of Bone Remodeling and Healing as Inspiration for Self-Repair in Materials

Round 1

Reviewer 1 Report

The manuscript "Mechanoregulation of bone remodeling and healing as inspiration for self-repair in materials" by Weinkamer, Eberl and Fratzl presents an interesting perspective on the control function that governs mechanically-regulated bone repair and applies the identified principles to designing biomimetic materials with potential for self-repair. I especially enjoyed the discussion of mechanoregulation during bone remodeling and fracture healing, and I believe that the focus of the function linking mechanical and biological aspects of regulation is unique is insightful. The discussion of biomimetics with self-repair capabilities is also interesting, although the links between the two parts can be improved (this is a very minor critic). The paper is well written, although a few typos were noted.

Author Response

The manuscript "Mechanoregulation of bone remodeling and healing as inspiration for self-repair in materials" by Weinkamer, Eberl and Fratzl presents an interesting perspective on the control function that governs mechanically-regulated bone repair and applies the identified principles to designing biomimetic materials with potential for self-repair. I especially enjoyed the discussion of mechanoregulation during bone remodeling and fracture healing, and I believe that the focus of the function linking mechanical and biological aspects of regulation is unique is insightful. The discussion of biomimetics with self-repair capabilities is also interesting, although the links between the two parts can be improved (this is a very minor critic). The paper is well written, although a few typos were noted.

We want to thank the reviewer for reviewing our manuscript and for providing helpful feedback. In the revised version of our manuscript we improved the link between the mechanoregulation of repair mechanisms in bone and the mechanoregulation of adaptive responses in synthetic materials by including a new figure (Figure 6). This new figure gives us the opportunity to show two synthetic materials with a mechanoregulated change in mechanical properties which is regulated quite differently compared to repair processes in bone. While in bone the control function displays a more gradual behavior between mechanical stimulus and the material’s response, the control function in both synthetic material is described by a much more discontinuous, step-like behavior. We hope that the figure also clarifies our motivation to choose as examples mechanical metamaterials and polymers including mechanophores.

Reviewer 2 Report

This perspective article provides a comprehensive overview of the studies on the mechanoregulation of bone remodeling and healing processes. The authors first set the big picture for general readers by introducing the general concept of adaptive materials controlled by positive/negative feedback loops. Then these concepts are applied to bone remodeling and healing processes respectively, and in-depth discussions are adequately covered for each topic from the biological mechanisms, theoretical models, and results from computational & experimental studies. These discussions are clear and easy to follow with comprehensive examples from previous studies.

The authors concluded this article with implications for synthetic self-healing materials. This is a critical section of this paper and may provide insights for bio-inspired design in a broad range of materials. The authors specifically listed two examples (programmable metamaterials and polymers including mechanophores) and provided very detailed discussion into the two topics. However, both two examples involve complicated material design and may not be familiar to the general readers. As a non-expert in metamaterials research, I find it not intuitive to fully understand the idea merely from the text descriptions in this manuscript. The authors may consider improving this part by including an additional figure depicting the basics in these two examples, as well as how they link to the discussions in this article.

Author Response

Reviewer 2:

This perspective article provides a comprehensive overview of the studies on the mechanoregulation of bone remodeling and healing processes. The authors first set the big picture for general readers by introducing the general concept of adaptive materials controlled by positive/negative feedback loops. Then these concepts are applied to bone remodeling and healing processes respectively, and in-depth discussions are adequately covered for each topic from the biological mechanisms, theoretical models, and results from computational & experimental studies. These discussions are clear and easy to follow with comprehensive examples from previous studies.

The authors concluded this article with implications for synthetic self-healing materials. This is a critical section of this paper and may provide insights for bio-inspired design in a broad range of materials. The authors specifically listed two examples (programmable metamaterials and polymers including mechanophores) and provided very detailed discussion into the two topics. However, both two examples involve complicated material design and may not be familiar to the general readers. As a non-expert in metamaterials research, I find it not intuitive to fully understand the idea merely from the text descriptions in this manuscript. The authors may consider improving this part by including an additional figure depicting the basics in these two examples, as well as how they link to the discussions in this article.

We want to thank the reviewer for reviewing our manuscript and for the important feedback. We fully agree with the reviewer that in our manuscript the transition from the mechanoregulation of repair mechanisms in bone to the mechanoregulation of adaptive responses in synthetic materials was rather challenging for a reader not familiar with mechanical metamaterials and polymers including mechanophores. Since it is our clear intention to address a broad readership, we follow the excellent suggestion of the reviewer to include an additional figure (Figure 6) in the revised version of our manuscript. Even for a reader without a background in the mechanics of materials and mechanochemistry, the new figure should illustrate how beyond a certain threshold value of the mechanical force the two materials change structurally: in the mechanical metamaterial by snapping through of a mechanically unstable structural element (Figure 6a and 6b) or by a ring-opening reaction of the mechanophore (Figure 6c). We hope that the figure also clarifies our motivation to choose these two examples with a similar step-like control function despite the very different length scales on which these materials show activity.