A novel approach to crosslink collagen-based scaffolds

Grp Photo_Macromolecular Bioscience_Weng Wan
From Left: From Left: Dr Le Quang Bach, Chan Weng Wan, Hariharan Ezhilarasu, Dr Deepak Choudhury

 

Science

Burn injuries are a serious medical issue affecting millions of people worldwide. When someone suffers a severe burn, doctors often use skin grafts (where healthy skin is taken from another part of the body to cover the wound). However, for patients with large burns, there may not be enough healthy skin available for grafting. Additionally, the wound may struggle to heal due to poor blood supply. To help with these issues, scientists have developed artificial skin substitutes called dermal regeneration templates (DRTs). These DRTs act as temporary scaffolds to support new tissue growth and improve healing. These DRTs typically are made from collagen, a natural protein in the skin, and are strengthened through a process called crosslinking. However, current methods of crosslinking are time-consuming and may also reduce the biological activity of the DRT. This study introduces a new way to strengthen collagen scaffolds using UV light first, then a chemical called glutaraldehyde (GA). This method also helps to tune the degradation of the scaffold’s structure. Additionally, it cuts the total process time in half—from 48 hours to just 24—compared to the older method.

 

Societal Impact

Our finding will eventually benefit burn patients and collagen-scaffold manufacturers by improving the cost-effectiveness of dermal regeneration templates. By reducing the intermediate processing time from 48 hours to 24 hours, our method would lower manufacturing costs and increase production capacity for the above-mentioned scaffolds; making these treatments more affordable and accessible.

 

Technical Summary

We have significantly reduced the crosslinking time for collagen-based dermal regeneration templates from 48 hours to 24 hours though by using both UV irradiation and GA treatment while retaining the bioactivity of the scaffold. The scaffolds crosslinked using our approach fall within the optimal pore size meant for dermal scaffolds (20-125 µm) verified via micro-CT data. In vitro data also confirm the effectiveness of this pore size distribution, facilitating cell infiltration and proliferation within our scaffold. The in vivo mouse model demonstrated that our scaffolds were able to achieve appropriate wound closure within 14 days and showed a similar extent of skin regeneration in both the dermis and epidermis when compared to a commercial scaffold.

Moreover, our scaffolds can be produced in various shapes (sheets, cylinders etc.) and sizes ranging from mm to cm which would not only be useful for burn wound solutions, but for broader tissue manufacturing applications.

Fig 1_Macromolecular Bioscience_Weng Wan

Figure 1. Collagen scaffolds of different shapes and sizes

 

Fig 2_Macromolecular Bioscience_Weng Wan

Figure 2. Hydrated crosslinked collagen sheet

 

References

Chan, W.W., Roy, K.R., Le, B.Q., Ezhilarasu, H., Zhang, X., Lim, R.Y.D., Banerjee, A., Kuriakose, M., Ng, K.J., Murugan, P. and Goh, C.T., 2024. A Novel Crosslinking Approach for Biomanufacturing of a Collagen‐Based Skin Dermal Template. Macromolecular Bioscience, p.2400457 (Cover Page of the Journal)