In article number 1801555, Wenguo Cui, Yuguang Zhang, Hélder A. Santos, Xiaoming Sun, and co-workers report the fabrication and investigation of the biological repair and healing effect of a multifunctional hydrogel, and optimization of its drug releasing and degradation property to match with the dynamic healing process of skin flap regeneration.
Background: Conventional reconstructive methods fail to achieve satisfactory results in total eyelid defect cases. Vascularized composite tissue allotransplantation might provide both good appearance and function for these patients. The structure of the eyelid is exceptional because it simultaneously consists of skin, connective tissue, the striated muscle, fiber structure, aponeuroses, and mucosa. Thus, before clinical application of eyelid allotransplantation, more experiments are needed to clarify the impact of ischemia, immunal suppressive agents, and deinnervation effects on these sophisticated structures. We developed an heterotopic periorbital transplantation model in rats to facilitate further experiment in this field. Methods: Twenty-five inbred male Lewis rats were used for anatomy study (n=10), and as donors or recipients of the operations (n=10). In the anatomy study, the vascular distribution and innervation to the periorbital unit was identified and recorded. Then, according to the anatomy study, 10 heterotopic transplantations and 2 transplantations with pedicle ligated were performed. The posterior facial vein and the external carotid artery are selected as the graft pedicle. All transplanted eyelids were assessed daily. Micro-CT scanning and hematoxylin and eosin staining of the grafts were performed 60 days after the operation. Results: All recipients tolerated the operation well. All grafts without pedicles ligated survived and new hair growth was observed. All of the transplanted eyelids were pink and pliable during the entire observation period, and we did not observe any signs of arterial or venous occlusion. In the recipients with graft pedicle ligated, the grafts were necrosed and mummified within 4 to 5 days. MicroCT of the survived grafts showed good blood supply and histologic staining revealed normal histologic morphologies. Conclusions: Our study proved the anatomical feasibility of periorbital transplantation by establishing a heterotopic transplantation model, which might facilitate future eyelid allotransplantation-related experiments.
Over the past few decades, biomaterials have made rapid advances in tissue engineering. In particular, there have been several studies on vascularization during skin flap regeneration for plastic surgery. From the perspective of function, the biomaterials used to improve the vascularization of skin flaps are primarily classified into two types: (1) electrospun nanofibrous membranes as porous scaffolds, and (2) hydrogels as cell or cytokine carriers. Based on their source, various natural, synthetic, and semi-synthetic biomaterials have been developed with respective characteristics. For the ischemic environment of the flap tissue, the therapeutic effect of the combination of biomaterials was better than that of drugs, cytokines, and cells alone. Biomaterials could improve cell migration, prolong the efficacy of cytokines, and provide an advantageous survival environment to transplanted cells.
Full-thickness skin grafts are widely used in plastic and reconstructive surgery. Their poor textural durability and associated contracture make them less desirable than skin flaps. Currently, stromal vascular fraction cells hold great promise because of their angiogenic potential, which may ameliorate the hypoxic period after skin grafting. In this study, autologous transplantation of stromal vascular fraction cells was used in combination with skin grafts to determine whether it improved the texture and other physical property of skin grafts.Stromal vascular fraction cells were isolated and injected under full-thickness skin grafts in a cohort of 20 rats; a second cohort of 20 rats served as controls. Skin grafts were harvested and analyzed on days 14, 30, and 90 after injections. Bioluminescent imaging with luciferase-stromal vascular fraction cells was used for cell tracing. Contracture ratios, elasticity modulus, and the stiffness of each graft were evaluated. Angiogenesis was evaluated using immunohistochemical techniques against vascular endothelial growth factor. Blood flow signals of the graft were also measured, and expression of vascular endothelial growth factor, hepatocyte growth factor, and basic fibroblast growth factor was assessed in all grafts.Stromal vascular fraction cells markedly decreased the contracture of skin grafts and improved their resilience and elasticity after 1 month. Histologically, the cells enhanced skin thickness and skin vascularization. Moreover, expression of vascular endothelial growth factor, basic fibroblast growth factor, and hepatocyte growth factor also increased in the stromal vascular fraction group.Autologous stromal vascular fraction cell transplantation enhances angiogenesis after skin grafting and improves the texture and elasticity of skin grafts.
Conditioned medium (CM) contains variety of factors secreted by cells, which directly regulate cellular processes, showing tremendous potential in regenerative medicine. Here, for the first time, we proposed a novel regenerative therapy mediated by biodegradable micro-nano electrospun fibers loaded with highly active conditioned medium of adipose-derived stem cells (ADSC-CM). ADSC-CM was successfully loaded into the nanofibers with biological protection and controllable sustained-release properties by emulsion electrospinning and protein freeze-drying technologies. In vitro, ADSC-CM released by the fibers accelerated the migration rate of fibroblasts; inhibited the over proliferation of fibroblasts by inducing apoptosis and damaging cell membrane; in addition, ADSC-CM inhibited the transformation of fibroblasts into myofibroblasts and suppressed excessive production of extracellular matrix (ECM). In vivo, the application of CM-biomaterials significantly accelerated wound closure and improved regeneration outcome, showing superior pro-regenerative performance. This study pioneered the application of CM-biomaterials in regenerative medicine, and confirmed the practicability and significant biological effects of this innovative biomaterials.
Abstract Organoids are three‐dimensional (3D) cell culture systems that simulate the structures and functions of organs, involving applications in disease modeling, drug screening, and cellular developmental biology. The material matrix in organoids can provide a 3D environment for stem cells to differentiate into different cell types and continuously self‐renew, thereby realizing the in vitro culture of organs, which has received extensive attention in recent years. However, some challenges still exist in organoids, including low maturity, high heterogeneity, and lack of spatiotemporal regulation. Therefore, in this review, we summarized the culturing protocols and various applications of stem cell‐derived organoids and proposed insightful thoughts for engineering stem cells into organoids in view of the current shortcomings, to achieve the further application and clinical translation of stem cells and engineered stem cells in organoid research.