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Tissue Engineering of Articular Cartilage
Published in Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi, Articular Cartilage, 2017
Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi
BMPs play a major role in endochondral bone formation and show general effects on cellular proliferation and matrix synthesis. As explained above, they are particularly attractive for cartilage engineering studies because they regulate both chondrogenesis and osteogenesis. Osteochondral integration is a critical factor in whether implants succeed or fail in vivo, so molecules that can stimulate this response are desirable (Pecina et al. 2002). As with TGF-β, BMPs can act synergistically with mechanical stimuli to accelerate regeneration of joint tissues. Currently, 20 types of BMPs have been identified, but only a subset has been examined for cartilage regeneration (Reddi 2003). BMPs generally have the ability to guide stem cells and immature bone and cartilage cells along the osteochondral pathway (O’Connor et al. 2000). BMP2 upregulated proteoglycan and collagen expression in chondrocytes (Gooch et al. 2002; Pecina et al. 2002; Valcourt et al. 2002), while also inducing better healing of defects in vivo (Frenkel et al. 2000; Pecina et al. 2002). BMP4 showed an ability to stimulate proteoglycan synthesis, bone formation, and cellular proliferation (Luyten et al. 1992; Pecina et al. 2002). BMP7 also showed positive effects on matrix synthesis (Pecina et al. 2002) and proliferation (Mattioli-Belmonte et al. 1999), while also decreasing type I collagen expression and suppressing infiltration of fibroblasts in vivo (Kaps et al. 2002). Articular chondrocytes treated with either BMP12 or 13 synthesized elevated levels of glycosaminoglycan, although these increases were less than that observed for cells treated with BMP2 (Gooch et al. 2002). Overall, experimental results have shown that BMPs have a generally positive effect on cartilage differentiation and morphogenesis, whether alone or in combination with other growth factors. For example, BMP2 application with IGF-1 resulted in more than onefold increases in aggregate modulus, accompanied by increases in glycosaminoglycan production, compared with controls (Elder and Athanasiou 2008).
Epidermal stimulating factors-gelatin/polycaprolactone coaxial electrospun nanofiber: ideal nanoscale material for dermal substitute
Published in Journal of Biomaterials Science, Polymer Edition, 2021
Li Yan, Haoyu Wang, Hui Xu, Rui Zheng, Zhengyu Shen
Several mediators play a critical role in the different stages of healing. For example, epidermal growth factor (EGF) promotes healing in the wound area by stimulating the migration and proliferation of epithelial cells and fibroblasts [9]. Hydrocortisone (HC) and ascorbic-2-phosphoric (Asc-2-P) have the capacity to promote keratinocyte growth. Bone morphogenetic protein-4 (BMP-4) and all-trans retinoic acid (ATRA) guide epithelial differentiation of stem cells. Petry introduced a combination protocol of the five bio-reagents for trans-differentiation of mesenchymal stem cells into the epidermal cell line, which showed significant upregulation of cytokeratin expression on two-dimensional and three-dimensional culture discs [10]. Their findings demonstrated that a combination of bio-reagents associated with skin wound healing can prove beneficial for skin regeneration. Incorporating growth factors into electrospun nanofiber scaffolds can increase the bioactivity of scaffolds by supplying suitable chemical or biological cues and increasing cellularisation. Therefore, we encapsulated EGF, HC, Asc-2-P, BMP-4 and ATRA, which were defined as epidermal stimulating (ES) factors, into gelatin/polycaprolactone (GT/PCL) electrospun nanofibers using coaxial electrospinning strategy to obtain ES-GT/PCL (Supplementary material Figure S1). ES-GT/PCL can induce mesenchymal epidermal transformation (Supplementary material Figure S2).