Oxidation-Responsive Supramolecular Hydrogels Based on Glucosamine Derivatives with an Aryl Sulfide Group.

Supramolecular hydrogels can be obtained via self-assembly of small molecules in aqueous environments. In this study, we describe the development of oxidation-responsive supramolecular hydrogels comprising glucosamine derivatives with an aryl sulfide group. We demonstrate that hydrogen peroxide can induce a gel-sol transition through the oxidation of the sulfide group to the corresponding sulfoxide. Furthermore, we show that this oxidation responsiveness can be extended to photo-responsiveness with the aid of a photosensitizer.

Insight on Oxygen-Supplying Biomaterials Used to Enhance Cell Survival, Retention, and Engraftment for Tissue Repair.

Oxygen is one of the essential requirements for cell survival, retention, and proliferation. The field of regenerative medicine and tissue engineering (TE) has realized considerable achievements for the regeneration of tissues. However, tissue regeneration still lacks the full functionality of solid organ implantations; limited cell survival and retention due to oxidative stress and hypoxia in the deeper parts of tissues remains a perpetual challenge. Especially prior to neovascularization, hypoxia is a major limiting factor, since oxygen delivery becomes crucial for cell survival throughout the tissue-engineered construct. Oxygen diffusion is generally limited in the range 100-200 µm of the thickness of a scaffold, and the cells located beyond this distance face oxygen deprivation, which ultimately leads to hypoxia. Furthermore, before achieving functional anastomosis, implanted tissues will be depleted of oxygen, resulting in hypoxia (<5% dissolved oxygen) followed by anoxic (<0.5% dissolved oxygen) microenvironments. Different types of approaches have been adopted to establish a sustained oxygen supply both in vitro and in vivo. In this review, we have summarized the recent developments in oxygen-generating and/or releasing biomaterials for enhancing cell survival in vitro, as well as for promoting soft and hard tissue repair, including skin, heart, nerve, pancreas, muscle, and bone tissues in vivo. In addition, redox-scavenging biomaterials and oxygenated scaffolds have also been highlighted. The surveyed results have shown significant promise in oxygen-producing biomaterials and oxygen carriers for enhancing cell functionality for regenerative medicine and TE applications. Taken together, this review provides a detailed overview of newer approaches and technologies for oxygen production, as well as their applications for bio-related disciplines.

Composite Superelastic Aerogel Scaffolds Containing Flexible SiO2 Nanofibers Promote Bone Regeneration.

Repairing irregular-shaped bone defects poses enormous challenges. Scaffolds that can fully fit the defect site and simultaneously induce osteogenesis and angiogenesis hold great promise for bone defect healing. This study aimed to produce superelastic organic/inorganic composite aerogel scaffolds by blending silica nanofibers (SiO2 ) and poly (lactic acid)/gelatin (PLA/gel) nanofibers; the content of SiO2 nanofibers is varied from 0-60 wt% (e.g., PLA/gel, PLA/gel/SiO2 -L, PLA/gel/SiO2 -M, and PLA/gel/SiO2 -H for 0%, 20%, 40%, and 60% of SiO2 nanofibers, respectively) to produce a range of scaffolds. The PLA/gel/SiO2 -M scaffold has excellent elasticity and good mechanical properties. In vitro experiments demonstrate that the silicon ions released from PLA/gel/SiO2 -M scaffolds promote the differentiation of rat bone marrow-derived mesenchymal stem cells into osteoblasts, enhancing alkaline phosphatase activity and bone-related genes expressions. The released silicon ions also promote the proliferation of human umbilical vein endothelial cells and the expression of vascular endothelial growth factors, thereby promoting angiogenesis. The assessment of these scaffolds in a calvarial defect model in rats shows good potential of PLA/gel/SiO2 -M to induce bone regeneration as well as promote osteogenesis and angiogenesis. Overall, these organic/inorganic composite scaffolds have good biological activity, which may have broad applications for tissue engineering.

Mechanobiological Strategies to Enhance Stem Cell Functionality for Regenerative Medicine and Tissue Engineering.

Stem cells have been extensively used in regenerative medicine and tissue engineering; however, they often lose their functionality because of the inflammatory microenvironment. This leads to their poor survival, retention, and engraftment at transplantation sites. Considering the rapid loss of transplanted cells due to poor cell-cell and cell-extracellular matrix (ECM) interactions during transplantation, it has been reasoned that stem cells mainly mediate reparative responses via paracrine mechanisms, including the secretion of extracellular vesicles (EVs). Ameliorating poor cell-cell and cell-ECM interactions may obviate the limitations associated with the poor retention and engraftment of transplanted cells and enable them to mediate tissue repair through the sustained and localized presentation of secreted bioactive cues. Biomaterial-mediated strategies may be leveraged to confer stem cells enhanced immunomodulatory properties, as well as better engraftment and retention at the target site. In these approaches, biomaterials have been exploited to spatiotemporally present bioactive cues to stem cell-laden platforms (e.g., aggregates, microtissues, and tissue-engineered constructs). An array of biomaterials, such as nanoparticles, hydrogels, and scaffolds, has been exploited to facilitate stem cells function at the target site. Additionally, biomaterials can be harnessed to suppress the inflammatory microenvironment to induce enhanced tissue repair. In this review, we summarize biomaterial-based platforms that impact stem cell function for better tissue repair that may have broader implications for the treatment of various diseases as well as tissue regeneration.