Nerve growth factor/angiogenin gene activated dermal bioscaffold for nerve repair in cutaneous wound healing

Min Yang^{¹^,²^,³^,^§}, Fang He^{¹^,²^,^§}, Chenghao Cai^{¹^,²^,^§}, Yiran Wang^{¹^,²}, Jiaming Shao^{¹^,²}, Wei Zhang^⁴, Ximing Zhu^⁵, Tingting Weng^⁶, Ronghua Jin^{¹^,²}, Tao Shen^⁷, Chunmao Han^{¹^,²}, Pan Wu^{¹^,²}(), Bin Yao^⁵(), Yuqi Zhang^{¹^,⁸}(), Xingang Wang^{¹^,²}()

1Department of Burns & Wound Care Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, China

2Zhejiang Key Laboratory of Trauma, Burn, and Medical Rescue, Hangzhou 310000, China

3Department of Wound Repair, Wound Repair and Regenerative Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China

4Department of Plastic Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, China

5Academy of Medical Engineering & Translational Medicine, Medical College, Tianjin University, Tianjin 300072, China

6Department of Burn & Plastic Surgery, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou 310000, China

7Department of Rehabilitation Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, China

8Zhejiang Provincial Key Laboratory for Advanced Drug Delivery Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China

^§ Min Yang, Fang He, and Chenghao Cai contributed equally to this work.

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This work fabricated a dermal scaffold with dual gene activity, promoting neurological function restoration, nerve repair, angiogenesis, and collagen deposition via over-expression of both nerve growth factor (NGF) and angiogenin (ANG) in situ, finally achieved high-quality wound healing.

Abstract

Patients with extensive and deep skin defects treated with dermal scaffolds usually emphasize the importance of rapid angiogenesis, while overlook the crucial role of skin nerves in regenerative repair. Insufficient early nerve regeneration not only impedes skin reinnervation and angiogenesis, but also damages the synergistic effects among them, eventually hinders healing quality. Nerve growth factor (NGF) has shown potent potential in peripheral nerve regeneration and promotion of angiogenesis. Angiogenin (ANG) is an independent angiogenic factor, supplying microenvironment needed for neurogenesis. This study presents a dermal scaffold with dual gene activity, fabricated by incorporating nanoparticles (NPs) composed of polyethylenimine (PEI)-chimeric plasmids encoding both NGF and ANG (PEI-plasmid NGF/ANG dermal scaffold (NADS)). Specifically, NADS achieves sustained and in situ release of these two factors, and encourages the repair cells to fulfill their regenerative roles. In vivo experiments confirm the efficacy of NADS in promoting fully functional innervated skin regeneration, inducing the fastest healing rates and rapidly facilitating the formation of a mature vascular network, thus resulting in high-quality wound healing. This approach offers an effective and comprehensive strategy for clinical application.

Keywords

cutaneous nerve repair nerve growth factor (NGF)dermal scaffolds angiogenin (ANG)neurological function restoration

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References

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Liu, T.; Qiu, C.; Ben, C.; Li, H. H.; Zhu, S. H. One-step approach for full-thickness skin defect reconstruction in rats using minced split-thickness skin grafts with Pelnac overlay. Burns Trauma 2019, 7, 19.