Composite Aerogel Scaffolds Containing Flexible Silica Nanofiber and Tricalcium Phosphate Enable Skin Regeneration.

Poor hemostatic ability and less vascularization at the injury site could hinder wound healing as well as adversely affect the quality of life (QOL). An ideal wound dressing should exhibit certain characteristics: (a) good hemostatic ability, (b) rapid wound healing, and (c) skin appendage formation. This necessitates the advent of innovative dressings to facilitate skin regeneration. Therapeutic ions, such as silicon ions (Si4+) and calcium ions (Ca2+), have been shown to assist in wound repair. The Si4+ released from silica (SiO2) can upregulate the expression of proteins, including the vascular endothelial growth factor (VEGF) and alpha smooth muscle actin (α-SMA), which is conducive to vascularization; Ca2+ released from tricalcium phosphate (TCP) can promote the coagulation alongside upregulating the expression of cell migration and cell differentiation related proteins, thereby facilitating the wound repair. The overarching objective of this study was to exploit short SiO2 nanofibers along with the TCP to prepare TCPx@SSF aerogels and assess their wound healing ability. Short SiO2 nanofibers were prepared by electrospinning and blended with varying proportions of TCP to afford TCPx@SSF aerogel scaffolds. The TCPx@SSF aerogels exhibited good cytocompatibility in a subcutaneous implantation model and manifested a rapid hemostatic effect (hemostatic time 75 s) in a liver trauma model in the rabbit. These aerogel scaffolds also promoted skin regeneration and exhibited rapid wound closure, epithelial tissue regeneration, and collagen deposition. Taken together, TCPx@SSF aerogels may be valuable for wound healing.

Synthesis of oxidized sodium alginate and its electrospun bio-hybrids with zinc oxide nanoparticles to promote wound healing.

Electrospun fibers provide a promising platform for wound healing; however, they lack requisite characteristics for wound repair, including antibacterial and anti-inflammatory properties and angiogenic ability. Sodium alginate (SA) is being used for different types of applications. However, the poor spinnability of SA restricts its applications. The objectives of this study were three-fold: a) to synthesize oxidized sodium alginate (OSA) to improve its spinnability, b) to fabricate composite fibrous membranes by blending OSA along with zinc oxide nanoparticles (ZnO-NPs), and c) to decipher antibacterial and anti-inflammatory properties as well as biocompatibility of membranes in vitro and in vivo. OSA displaying different oxidation degrees (Dox (%)) was synthesized by varying the molar ratio of sodium periodate to SA. OSA (Dox, ∼48 %) afforded smooth and uniform fibers; 0.5 wt% of adipic dihydrazide (ADH) evolved into structurally stable and water-insoluble membranes. Composite fibrous membranes containing 2 wt% of ZnO-NPs displayed good biocompatibility and bactericidal effect against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in vitro. In addition, composite membranes showed remarkable epithelialization, neovascularization, and anti-inflammatory response than that of the membranes devoid of ZnO-NPs. Conclusively, these composite fibrous membranes may have broad implications for wound healing applications.

Vascular Endothelial Growth Factor-Capturing Aligned Electrospun Polycaprolactone/Gelatin Nanofibers Promote Patellar Ligament Regeneration.

Ligament injuries are common in sports and other rigorous activities. It is a great challenge to achieve ligament regeneration after an injury due the avascular structure and low self-renewal capability. Herein, we developed vascular endothelial growth factor (VEGF)-binding aligned electrospun poly(caprolactone)/gelatin (PCL/Gel) scaffolds by incorporating prominin-1-binding peptide (BP) sequence and exploited them for patellar ligament regeneration. The adsorption of BP onto scaffolds was discerned by various techniques, such as Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, and confocal laser scanning microscope. The accumulation of VEGF onto scaffolds correlated with the concentration of the peptide in vitro. BP-anchored PCL/Gel scaffolds (BP@PCL/Gel) promoted the tubular formation of human umbilical vein endothelial cells (HUVECs) and wound healing in vitro. Besides, BP containing scaffolds exhibited higher content of CD31+ cells than that of the control scaffolds at 1 week after implantation in vivo. Moreover, BP containing scaffolds improved biomechanical properties and facilitated the regeneration of matured collagen in patellar ligament 4 weeks after implantation in mice. Overall, this strategy of peptide-mediated orchestration of VEGF provides an enticing platform for the ligament regeneration, which may also have broad implications for tissue repair applications. STATEMENT OF SIGNIFICANCE: Ligament injuries are central to sports and other rigorous activities. Given to the avascular nature and poor self-healing capability of injured ligament tissues, it is a burgeoning challenge to fabricate tissue-engineered scaffolds for ligament reconstruction. Vascular endothelial growth factor (VEGF) is pivotal to the neo-vessel formation. However, the high molecular weight of VEGF as well as its short half-life in vitro and in vivo limits its therapeutic potential. To circumvent these limitations, herein, we functionalized aligned electrospun polycaprolactone/gelatin (PCL/Gel)-based scaffolds with VEGF-binding peptide (BP) and assessed their biocompatibility and performance in vitro and in vivo. BP-modified scaffolds accumulated VEGF, improved tube formation of HUVECs, and induced wound healing in vitro, which may have broad implications for regenerative medicine and tissue engineering.

Reactive Oxygen Species-Based Biomaterials for Regenerative Medicine and Tissue Engineering Applications.

Reactive oxygen species (ROS), acting as essential mediators in biological system, play important roles in the physiologic and pathologic processes, including cellular signal transductions and cell homeostasis interference. Aberrant expression of ROS in tissue microenvironment can be caused by the internal/external stimuli and tissue injury, which may leads to an elevated level of oxidative stress, inflammatory response, and cellular damage as well as disruption in the tissue repair process. To prevent the formation of excess ROS around the injury site, advanced biomaterials can be remodeled or instructed to release their payloads in an injury microenvironment-responsive fashion to regulate the elevated levels of the ROS, which may also help downregulate the oxidative stress and promote tissue regeneration. A multitude of scaffolds and bioactive cues have been reported to promote the regeneration of damaged tissues based on the scavenging of free radicals and reactive species that confer high protection to the cellular activity and tissue function. In this review, we outline the underlying mechanism of ROS generation in the tissue microenvironment and present a comprehensive review of ROS-scavenging biomaterials for regenerative medicine and tissue engineering applications, including soft tissues regeneration, bone and cartilage repair as well as wound healing. Additionally, we highlight the strategies for the regulation of ROS by scaffold design and processing technology. Taken together, developing ROS-based biomaterials may not only help develop advanced platforms for improving injury microenvironment but also accelerate tissue regeneration.