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Tissue-engineered skin (TES), as an analogue of native skin, is promising for wound repair and regeneration. However, a major drawback of TES products is a lack of skin appendages and nerves to enhance skin healing, structural integrity and skin vitality. Skin appendages and nerves are important constituents for fully functional skin. To date, many studies have yielded remarkable results in the field of skin appendages reconstruction and nerve regeneration. However, patients often complain about a loss of skin sensation and even cutaneous chronic pain. Restoration of pain, temperature, and touch perceptions should now be a major challenge to solve in order to improve patients' quality of life. Current strategies to create skin appendages and sensory nerve regeneration are mainly based on different types of seeding cells, scaffold materials, bioactive factors and involved signaling pathways. This article provides a comprehensive overview of different strategies for, and advances in, skin appendages and sensory nerve regeneration, which is an important issue in the field of tissue engineering and regenerative medicine.

Critical tissue defects frequently result from trauma, burns, chronic wounds and/or surgery. The ideal treatment for such tissue loss is autografting, but donor sites are often limited. Tissue engineering (TE) is an inspiring alternative for tissue repair and regeneration (TRR). One of the current state-of-the-art methods for TRR is gene therapy. Non-viral gene delivery systems (nVGDS) have great potential for TE and have several advantages over viral delivery including lower immunogenicity and toxicity, better cell specificity, better modifiability, and higher productivity. However, there is no ideal nVGDS for TRR, hence, there is widespread research to improve their properties. This review introduces the basic principles and key aspects of commonly-used nVGDSs. We focus on recent advances in their applications, current challenges, and future directions.

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