Microfluidic-Based Droplets for Advanced Regenerative Medicine: Current Challenges and Future Trends.

Microfluidics is a promising approach for the facile and large-scale fabrication of monodispersed droplets for various applications in biomedicine. This technology has demonstrated great potential to address the limitations of regenerative medicine. Microfluidics provides safe, accurate, reliable, and cost-effective methods for encapsulating different stem cells, gametes, biomaterials, biomolecules, reagents, genes, and nanoparticles inside picoliter-sized droplets or droplet-derived microgels for different applications. Moreover, microenvironments made using such droplets can mimic niches of stem cells for cell therapy purposes, simulate native extracellular matrix (ECM) for tissue engineering applications, and remove challenges in cell encapsulation and three-dimensional (3D) culture methods. The fabrication of droplets using microfluidics also provides controllable microenvironments for manipulating gametes, fertilization, and embryo cultures for reproductive medicine. This review focuses on the relevant studies, and the latest progress in applying droplets in stem cell therapy, tissue engineering, reproductive biology, and gene therapy are separately evaluated. In the end, we discuss the challenges ahead in the field of microfluidics-based droplets for advanced regenerative medicine.

In vitro and in vivo evaluation of electrospun cellulose acetate/gelatin/hydroxyapatite nanocomposite mats for wound dressing applications.

The present study aimed to evaluate the efficacy of cellulose acetate/gelatin/nanohydroxyapatite (CA/Gel/nHA) nanocomposite mats as the wound dressing. The dressings were prepared with electrospinning of CA/Gel solutions containing 12.5, 25 and 50 mg nHA. The dressings were evaluated regarding their water uptake capacity, morphology, tensile strength, water vapour transmission rate, wettability and cellular response with L929 cell line. The results showed that the concentration of nHA had a direct correlation with porosity, water contact angle, water uptake, water vapor transmission rate and proliferation. In vivo studies showed that all dressings had higher wound closure percent than the sterile gauze, as the control. The highest wound closure value was achieved in the CA/Gel +25 mg nHA group, which showed 93.5 ± 1.6%. The histological and the histomorphometric examinations of the wounds revealed that the CA/Gel +25 mg nHA dressing had the greatest collagen synthesis, re-epithelialization, neovascularization and also the best cosmetic appearance. Based on our finding, it could be concluded the applicability of electrospun nanofibrous CA/Gel/nHA dressings for successful wound treatment.

Three-dimensional wet-electrospun poly(lactic acid)/multi-wall carbon nanotubes scaffold induces differentiation of human menstrual blood-derived stem cells into germ-like cells.

Infertility caused by the disruption or absence of germ cells is a major and largely incurable medical problem. Germ cells (i.e., sperm or egg) play a key role in the transmission of genetic and epigenetic information across generations. Generation of gametes derived in vitro from stem cells hold promising prospects which could potentially help infertile men and women. Menstrual blood-derived stem cells are a unique stem cell source. Evidence suggests that menstrual blood-derived stem cells exhibit a multi-lineage potential and have attracted extensive attention in regenerative medicine. To maintain the three-dimensional structure of natural extra cellular matrices in vitro, scaffolds can do this favor and mimic a microenvironment for cell proliferation and differentiation. According to previous studies, poly(lactic acid) and multi-wall carbon nanotubes have been introduced as novel and promising biomaterials for the proliferation and differentiation of stem cells. Some cell types have been successfully grown on a matrix containing carbon nanotubes in tissue engineering but there is no report for this material to support stem cells differentiation into germ cells lineage. This study designed a 3D wet-electrospun poly(lactic acid) and poly(lactic acid)/multi-wall carbon nanotubes composite scaffold to compare infiltration, proliferation, and differentiation potential of menstrual blood-derived stem cells toward germ cell lineage with 2D culture. Our primary data revealed that the fabricated scaffold has mechanical and biological suitable qualities for supporting and attachments of stem cells. The differentiated menstrual blood-derived stem cells tracking in scaffolds using scanning electron microscopy confirmed cell attachment, aggregation, and distribution on the porous scaffold. Based on the differentiation assay by RT-PCR analysis, stem cells and germ-like cells markers were expressed in 3D groups as well as 2D one. It seems that poly(lactic acid)/multi-wall carbon nanotubes scaffold-seeded menstrual blood-derived stem cells could be viewed as a novel, safe, and accessible construct for these cells, as they enhance germ-like generation from menstrual blood-derived stem cells.

Cerium oxide nanoparticle-containing poly (ε-caprolactone)/gelatin electrospun film as a potential wound dressing material: In vitro and in vivo evaluation.

In the present study, cerium oxide (CeO2) nanoparticles were incorporated into poly (ε-caprolactone)/gelatin films in order to develop a potential wound dressing material. The wound dressings were prepared by electrospinning of poly (ε-caprolactone)/gelatin (1:1 (w/w)) solutions containing 1.50%, 3% and 6% (w/w) CeO2 nanoparticles. The electrospun films were evaluated regarding their morphology, contact angle, water-uptake capacity, water vapor transmission rate, tensile strength and cellular response. The film containing 1.50% CeO2 nanoparticles was chosen as the optimal dressing for the in vivo study on full-thickness excisional wounds of rats. The study showed that after 2weeks, the wounds treated with the CeO2 nanoparticle-containing dressing achieved a significant closure to nearly 100% compared with the sterile gauze with the nearly 63% of wound closure. Our results provided evidence supporting the possible applicability of CeO2 nanoparticle-containing wound dressing for a successful wound treatment.