Despite clinical applications of the first‐generation tissue adhesives and hemostats, the correlation among microstructure and hemostasis of hydrogels with wound healing is less understood and it is elusive to design high‐performance hydrogels to meet worldwide growing demands in wound closure, hemostasis, and healing. Inspired by the microstructure of extracellular matrix and mussel‐mimetic chemistry, two kinds of coordinated and covalent glycopolypeptide hydrogels are fabricated, which present tunable tissue adhesion strength (14.6–83.9 kPa) and microporous structure (8–18 µm), and lower hemolysis <1.5%. Remarkably, the microporous size mainly controls the hemostasis, and those hydrogels with larger pores of 16–18 µm achieve the fastest hemostasis of ≈14 s and the lowest blood loss of ≈6% than fibrin glue and others. Moreover, both biocompatibility and hemostasis affect wound healing performance, as assessed by hemolysis, cytotoxicity, subcutaneous implantation, and hemostasis and healing assays. Importantly, the glycopolypeptide hydrogel‐treated rat‐skin defect model achieves full wound closure and regenerates thick dermis and epidermis with some hair follicles on day 14. Consequently, this work not only establishes a versatile method for constructing glycopolypeptide hydrogels with tunable adhesion and microporous structure, fast hemostasis, and superior healing functions, but also discloses a useful rationale for designing high‐performance hemostatic and healing hydrogels.
In clinic, strontium ranelate (SrR) is a useful drug to treat osteoporosis by orally taken method, but some side effect appeared in recent years. The aim of this study is to evaluate the effectiveness and safety of SrR on cells by direct application, to study the possibility of local application of this drug. Qualitative ALP staining, quantitative ALP activity assay, alizarin red staining, realtime PCR and westernblot assay were used to evaluate the osteogenesis ability of SrR under normal or osteogenic induction environment of ovariectomy bone marrow mesenchymal stem cells (OVX-BMSCs). The angiogenesis ability of SrR was studied by immunofluorescence staining of CD31 and vWF of OVX-BMSCs under angiogenesis induction environment, transwell, tubeformation and realtime PCR assay of HUVECs. Signaling pathway of PI3K/AKT/mTOR was also studied. The result demonstrated that SrR could enhance proliferation and osteogenic differentiation of OVX-BMSCs. The osteogenesis effect of SrR has been proved by the better performed of ALP activity, alizarin red staining and the remarkable up-regulation of ALP, Col-I, Runx2, OCN, BMP-2, BSP, OPG of the OVX-BMSCs, and reduction of RANKL. In addition, SrR promotes angiogenesis differentiation of both OVX-BMSCs and HUVECs. Higher intensity of immunostaining of CD31 and vWF, better result of transwell and tubeformation assay could be observed in SrR treated group, and increasing mRNA levels of VEGF and Ang-1 in the OVX-BMSCs, VEGF in HUVECs were learnt. Signaling pathway assay showed that PI3K/AKT/mTOR signaling pathway was involved in this SrR triggered angiogenesis procedure. The thrombosis marker ET-1, PAI-1 and t-PA were up-regulated, but no significant differences for low concentration (<0.5mM). The concentration between 0.25-0.5mM may be more appropriate for local application, and locally application of SrR could be considered as a promising way for bone regeneration.
Platelet aggregates, such as PRP, PRF, and CGF, have been used alone or in combination with other grafting materials to enhance restoration outcomes. The process for preparing these autografting materials requires two-step centrifugation or specific centrifuges. In this study, we obtained an injectable fibrin scaffold (IFS) rich in growth factors by one-step centrifugation of whole blood from rabbits. The purpose of this study is to introduce some characteristics of IFS. This scaffold was characterized using various techniques, including Masson’s trichrome staining, scanning electron microscopy, porosity measurements, and cell counting. The sustained release of growth factors, including PDGF, VEGF, TGF-β1, IGF, FGF, and EGF, was quantified using ELISA assay. The obtained IFS was tested for its effects on cell proliferation, extracellular matrix deposition, and full-thickness skin defect repair. The prepared IFS is characterized by a loose fibrin network structure with white blood cells and platelets that slowly release growth factors and can promote the healing of skin defects via the promotion of cell proliferation, collagen deposition, and tissue revascularization. In addition, its liquid properties and porous structure are conducive to its application as a therapeutic component in tissue engineering.
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