Jiangsu Trautec Medical Technology Co., Ltd.

Androgenetic alopecia (AGA), the preeminent form of clinical hair loss, poses a significant challenge to patients. Growth factors (GFs) have been investigated for the treatment of hair loss. However, the issue of their optimal intra-dermal delivery remains a formidable obstacle. Type XVII collagen (COL17), which plays a crucial role in regulating the hair follicle aging process, has emerged as a highly promising candidate for hair loss treatment. Considering these constraints, we developed an IGF-1 loaded borate-modified rhCOL17 MN platform (I-mCOL17 MNs) for the treatment of AGA. The mCOL17 MNs are engineered to precisely control the release of bioactive payloads in response to dynamic changes in the microenvironment. A comprehensive investigation was conducted to verify the physicochemical characteristics, as well as the in vitro and in vivo biological activities of the MNs. Our findings demonstrate that, when contrasted with the clinically utilized drug minoxidil, our MN exhibits a remarkable capacity to enhance neovascularization, alleviate tissue-based inflammatory responses, and promote hair regeneration in murine models of AGA. Overall, this MN represents a novel, safer, and more efficient strategy for the treatment of AGA, offering new hope for patients suffering from this prevalent condition.

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.

To investigate the effects of recombinant human type XVII collagen (RHCXVII) on the proliferation and adhesion of primary human keratinocytes (HPKCs) and to observe its clinical efficacy and safety in bullous pemphigoid (BP).

The RHCXVII was produced by genetic recombination technology and characterized by Fourier transform infrared (FTIR) spectroscopy. HPKCs were obtained from human foreskin and seeded onto culture plates coated with RHCXVII at concentrations of 10, 50 and 100μg/ml. The proliferation and relative adhesion of HPKCs were assessed by Cell Counting Kit-8 (CCK-8) and adhesion assays, respectively. Trajectories and velocities of HPKCs were recorded using a living cell imaging platform. To assess the effects of RHCXVII on HPKCs, E-cadherin, integrinα6 and laminin α3 mRNA levels were measured using reverse transcription-polymerase chain reaction (RT-PCR) assays. The patient test sites were treated with RHCXVII, while the contralateral sides served as controls. This was performed in combination with systemic glucocorticoid treatment. Bilateral wound healing was recorded at various time points and the efficacy in BP was assessed.

RHCXVII exhibited the anticipated structural characteristics of recombinant collagen and was deemed suitable for utilization in the present study. HPKCs demonstrated robust growth in culture plates precoated with RHCXVII, expressing keratin 15 (K15). After 3, 5 and 7 days, RHCXVII at a concentration of 10 µg/ml significantly promoted the proliferation of HPKCs (P<0.05). Furthermore, the optimal relative adhesion of HPKCs was observed when cells were cultured on RHCXVII at a concentration of 100 µg/ml (P<0.01). The mRNA levels of E-cadherin, integrinα6 and lamininα3 in HPKCs cultivated in wells coated with RHCXVII were considerably higher compared to the control group (P<0.05). The study encompassed a total of 12 patients. The mean time to resolution of lesions on the treated sides was 11.08 days, significantly shorter than the 13.42 days observed on the control sides. The mean time to blister resolution was 2.3 days shorter on the treated sides than on the controls. By day 7, the percentage improvement in wound healing compared to the baseline was 7.75 % greater on the treated sides than on the control sides. The study noted a high level of patient satisfaction and no occurrence of significant adverse events.

RHCXVII has the capacity to promote HPKC growth and adherence. In clinical applications, it has been demonstrated to accelerate wound healing in patients with bullous diseases (BD), thereby reducing the risk of subsequent secondary infection. Its potential as an adjunct treatment for wound repair in diseases such as BD merits further investigation.