Microenvironment-responsive recombinant collagen XVII-based composite microneedles for the treatment of androgenetic alopecia.

Androgenetic alopecia (AGA) is the most prevalent form of hair loss worldwide. Growth factors have been used to treat hair loss, but their intradermal delivery remains challenging. Type XVII collagen (COL17) has been reported to regulate the aging process of hair follicles (HFs). We reason that combining the therapeutic efficacy of growth factors and collagen biomaterials will provide maximal hair regeneration. Here, we design a microenvironment-responsive recombinant human COL17 microneedle (MRrhCOL17 MN) system for the transdermal delivery of the insulin-like growth factor-1 (IGF-1) to stimulate hair growth. We load IGF-1 into mesoporous polydopamine nanoparticles (MPDAs) to allow for continuous release of the growth factor. When applied to the skin, the composite MNs penetrate the skin, release IGF-1 and rhCOL17 in response to the alteration of the microenvironment and photothermal effect, and stimulate hair growth in a mouse model of AGA. Compared with the clinical drug minoxidil, our MN system more effectively enhances neovascularization, alleviates tissue inflammatory responses, and promotes hair regeneration in AGA mice. These therapeutic effects have been linked to the activation of the VEGF/VEGFR and Src/p38 MAPK signaling pathways. Taken together, the composite MRrhCOL17 MN thereby offers a new option for intractable AGA patients. STATEMENT OF SIGNIFICANCE: Growth factors hold the potential to effectively stimulate the growth of hair follicles; however, their transdermal delivery remains a formidable challenge. In this study, recombinant human type XVII collagen (rhCOL17) is employed as the primary scaffolding material to fabricate microneedles (MNs) for the delivery of insulin-like growth factor 1 (IGF-1), with the aim of promoting hair follicle regeneration. Additionally, the concept of microenvironmental responsiveness is integrated to enable the controlled release of IGF-1 from the MNs. Moreover, the low-temperature photothermal effect of nanoparticles is harnessed to optimize the process of hair regeneration, thereby maximizing the outcome of hair follicle rejuvenation.