Scalable and high-throughput production of an injectable platelet-rich plasma (PRP)/cell-laden microcarrier/hydrogel composite system for hair follicle tissue engineering.

Scalable and high-throughput production of an injectable platelet-rich plasma (PRP)/cell-laden microcarrier/hydrogel composite system for hair follicle tissue engineering.
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DOI:
10.1186/s12951-022-01671-8
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发表时间:
2022-11-03
影响因子:
10.2
通讯作者:
Miao, Yong
Miao, Yong
中科院分区:
工程技术1区
文献类型:
--
作者:
Zhang, Yufan;Yin, Panjing;Huang, Junfei;Yang, Lunan;Liu, Zhen;Fu, Danlan;Hu, Zhiqi;Huang, Wenhua;Miao, Yong

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毛囊组织工程在脱发治疗方面具有巨大的潜力。然而,仍然存在一些挑战,包括毛乳头细胞(DPC)活性、增殖和HF诱导性的减弱,以及为生物分子或细胞生成类似细胞外基质(ECM)底物所需的相关低效和繁琐的准备过程。在此,我们利用明胶甲基丙烯酰基(GelMA)和壳聚糖水凝胶,在高通量的微流控芯片上制备了可扩展、单分散、直径可控的GelMA/壳聚糖微载体(IGMs),负载了富血小板血浆(PRP)和种子DPC。用于IGM的仿ECM水凝胶具有表面纳米级的形貌和高的孔隙率。通过调节油水相流量比,实现了直径不同、精度较高的IGMS的批量生产。此外,IGM表现出适当的肿胀和持续的生长因子释放,以促进相对较长的毛发生长阶段。种植在PRP负载的 上的DPC表现出良好的活性(>DPC 90%)、黏附、铺展和增殖特性(是对照组的1.2%)。重要的是,与对照组和IGMS组相比,携带PRP的IGMS在体外显示出更高的DPC的毛发诱导性(p < 0.05)。此外,负载DPC/PRP的IGM与负载EPC的GelMA有效地混合形成负载PRP的DPC/EPC共培养水凝胶系统(DECHS),并将其注射到裸鼠皮下。携带PRP的DECHS产生的HFs(~ 35个/部位)和新血管(~ 12个/部位)明显多于其他组(p 和lt; 各0.05)。综上所述,这些结果表明,基于高通量微流控技术,我们获得了可规模和可控的模拟细胞外基质的IGMs和DECHS的生产,模拟了有效的微观和宏观环境来促进DPC的生物活性和毛发再生,从而为HF组织工程提供了一种潜在的新策略。网上版载有补充材料,可在10.1186/s12951-022-01671-8查阅。
Tissue engineering of hair follicles (HFs) has enormous potential for hair loss treatment. However, certain challenges remain, including weakening of the dermal papilla cell (DPC) viability, proliferation, and HF inducibility, as well as the associated inefficient and tedious preparation process required to generate extracellular matrix (ECM)-mimicking substrates for biomolecules or cells. Herein, we utilized gelatin methacryloyl (GelMA) and chitosan hydrogels to prepare scalable, monodispersed, and diameter-controllable interpenetrating network GelMA/chitosan-microcarriers (IGMs) loaded with platelet-rich plasma (PRP) and seeded with DPCs, on a high-throughput microfluidic chip. The ECM-mimicking hydrogels used for IGMs exhibited surface nano-topography and high porosity. Mass production of IGMs with distinct and precise diameters was achieved by adjusting the oil and aqueous phase flow rate ratio. Moreover, IGMs exhibited appropriate swelling and sustained growth factor release to facilitate a relatively long hair growth phase. DPCs seeded on PRP-loaded IGMs exhibited good viability (> 90%), adhesion, spreading, and proliferative properties (1.2-fold greater than control group). Importantly, PRP-loaded IGMs presented a higher hair inducibility of DPCs in vitro compared to the control and IGMs group (p < 0.05). Furthermore, DPC/PRP-laden IGMs were effectively mixed with epidermal cell (EPC)-laden GelMA to form a PRP-loaded DPC/EPC co-cultured hydrogel system (DECHS), which was subcutaneously injected into the hypodermis of nude mice. The PRP-loaded DECHS generated significantly more HFs (~ 35 per site) and novel vessels (~ 12 per site) than the other groups (p < 0.05 for each). Taken together, these results illustrate that, based on high-throughput microfluidics, we obtained scalable and controllable production of ECM-mimicking IGMs and DECHS, which simulate an effective micro- and macro-environment to promote DPC bioactivity and hair regeneration, thus representing a potential new strategy for HF tissue engineering. The online version contains supplementary material available at 10.1186/s12951-022-01671-8.
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影响因子: 4.6
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