3D-engineering of Cellularized Conduits for Peripheral Nerve Regeneration

Hu, Yu; Wu, Yinsu; Gou, Zhiyuan; Tao, Jie; Zhang, Jiumeng; Liu, Qianqi; Kang, Tianyi; Jiang, Shu; Huang, Siqing; He, Jiankang; Chen, Shaochen; Du, Yanan; Gou, Maling

doi:10.1038/srep32184

Cited by 118 publications

(104 citation statements)

References 52 publications

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“…Co-culture can be comprised of heterogeneous cells to cells; cells with specific GFs or other pharmacologic agents; and cells to drive the behavior of other cells. [19],[20],[50],[51],[68]–[73] Any use of these cells as models are possible if some type of suitable platform is available that will enable them to attach and perform their function. Therefore, 3D cell culture success depends on the matrix to be seeded, such as the polymeric scaffolds that offer the 3D structures.…”

Section: Selection Of Cellsmentioning

confidence: 99%

“…[73] The choice of material is crucial on 3D printing technology specially on inkjet bioprinting, since it needs to be printed liquid and then form a solid 3D structure. 3D structure is achieved by the use of materials that can be cross-linked after the deposition by chemical, pH or ultraviolet mechanisms.…”

Section: D Cell Culture Techniquesmentioning

confidence: 99%

“…Gelatin methacryloyl (GelMA), is one of the chosen material for the desktop 3D printer application. [73] The developed cryoGelMA, named after the conduit preparation via cryopolymerization, is turned into a bio-conduit by the introduction of multipotent adipose-derived stem cells (ADSCs) to generate local environment to foment the regeneration of axons, which is possible with the use of 3D printing. The versatility of 3D printing is taken as an advantage to engineer conduits of different geometries such as multichannel or bifurcating and even personalized structures.…”

Section: D Cell Culture Techniquesmentioning

confidence: 99%

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Polymeric scaffolds for three-dimensional culture of nerve cells: a model of peripheral nerve regeneration

et al. 2017

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Understanding peripheral nerve repair requires the evaluation of 3D structures that serve as platforms for 3D cell culture. Multiple platforms for 3D cell culture have been developed, mimicking peripheral nerve growth and function, in order to study tissue repair or diseases. To recreate an appropriate 3D environment for peripheral nerve cells, key factors are to be considered including: selection of cells, polymeric biomaterials to be used, and fabrication techniques to shape and form the 3D scaffolds for cellular culture. This review focuses on polymeric 3D platforms used for the development of 3D peripheral nerve cell cultures.

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Section: Selection Of Cellsmentioning

confidence: 99%

Section: D Cell Culture Techniquesmentioning

confidence: 99%

Section: D Cell Culture Techniquesmentioning

confidence: 99%

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Polymeric scaffolds for three-dimensional culture of nerve cells: a model of peripheral nerve regeneration

et al. 2017

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“…However, some drawbacks such as misalignment of nerve bundles, curling of nerve ends, or the proliferation of connective tissue at anastomotic sites still complicate treatments (Nakayama et al, 2007). Noteworthy, Gou and collaborators (Hu et al, 2016) described the use of GelMA and ADSCs to facilitate rat sciatic nerve repair. Gelatin can be cross-linked with genipin (Chen et al, 2005) and EDC-NHS (Chang et al, 2007) or under the form of GelMA-LAP (Xia et al, 2018;Zhou, Lee, & Tan, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, results between the composite conduit group and the autograft group were of no statistical differences.All results above showed that the composite conduit filled with EHS Hydrogel can promote the repair of peripheral nerve and may become a promising way to treat peripheral nerve defects.3D bioprint, chemical cross-link, ECM, GelMA, nerve repair Conduits were produced as described earlier (Hu et al, 2016). To date, commercially available artificial nerve conduits comprise hollow tubes.…”

mentioning

confidence: 99%

3D‐engineered GelMA conduit filled with ECM promotes regeneration of peripheral nerve

Gong

Fei

et al. 2019

J Biomedical Materials Res

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Autologous transplantation remains the golden standard for peripheral nerve repair.However, many drawbacks, such as the risk of reoperation or nerve injury remain associated with this method. To date, commercially available artificial nerve conduits comprise hollow tubes. By providing physical guiding and biological cues, tissue engineered conduits are promising for bridging peripheral nerve defects. The present study focuses on the preparation of artificial composite nerve conduits by 3D bio-printing. 3D-printed molds with a tubular cavity were filled with an Engelbreth-Holm-Swarm (EHS) Hydrogel mimicking the extracellular matrix (ECM) basement membrane. Chemically cross-linked gelatin methacryloyl (GelMA) was used to form the conduit backbone, while EHS Hydrogels improved nerve fiber growth while shortening repair time. Statistical significant difference had been found between the blank conduit and the composite conduit group on compound muscle action potential after 4 months. On the other hand, results between the composite conduit group and the autograft group were of no statistical differences.All results above showed that the composite conduit filled with EHS Hydrogel can promote the repair of peripheral nerve and may become a promising way to treat peripheral nerve defects.3D bioprint, chemical cross-link, ECM, GelMA, nerve repair Conduits were produced as described earlier (Hu et al., 2016). Briefly, the mold (Figure 1a,b) was modeled with the use of SolidWorks to create a tubular cavity prior to 3D printing. Based on the size of rat sciatic nerves, the inner and outer diameters were 2 and 4 mm, respectively (Zhao et al., 2016). Five percentage of GelMA (SE-3DP-0200, StemEasy Biotech, China) aqueous solution was prepared at 60 C. After complete dissolution, the solution was cooled to 15 C prior to the addition of 0.5% APS and 0.1% TEMED. The mixture was then poured into the mold and rapidly placed at −20 C. After 24 hr of solidification, the conduit was defrosted and unmolded, followed by intensive rinsing and freeze-drying.For EHS Hydrogel (SE-EHS-0100, StemEasy Biotech, China) filling, conduits were placed on precooled petri-dishes and 0.1 ml of EHS Hydrogel was poured into the cavity. Conduits were then immediately placed in an incubator. After 5 min, the EHS Hydrogel displayed a jellylike texture and the composite conduit was considered ready to use.According to the conventional method, the blank GelMA conduit was examined by scanning electron microscopy (SEM, Phenom ProX, Thermo fisher), and the images were analyzed by ImageJ to calculate the porosity. The blank conduits were immersed in saline in 37 C, and the swelling ratio was calculated by weighing before and after at different time points and calculated by the following formula (Zhao et al., 2016):Swelling ratio = wet weight− dry weight dry weight × 100%The mechanical properties of GelMA blank conduits were also evaluated by both compression and tensile tests using universal testing systems (5969, Instron, United States) equipped with a 50 N loa...

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Advanced Functional Biomaterials for Stem Cell Delivery in Regenerative Engineering and Medicine

Wang

Rivera‐Bolanos

Jiang

et al. 2019

Adv Funct Materials

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Stem cell-based therapies can potentially regenerate many types of tissues and organs, thereby providing solutions to a variety of diseases and injuries. However, acute cell death, uncontrolled differentiation, and low functional engraftment yields remain critical obstacles for clinical translation. Advanced functional biomaterial scaffolds that can deliver stem cells to the targeted tissues/organs and promote stem cell survival, differentiation, and integration to host tissues may potentially transform the clinical outcome of stem cellbased regenerative therapies. In this review, the authors briefly summarize sources of stem cells for transplantation, present the current state of the art in biomaterial design for stem cell delivery, and provide critical analysis for existing materials. Applications to the cardiovascular, neural, and musculoskeletal systems are highlighted with recent nonclinical studies and clinical trials. The authors also discuss how advances in biomaterials research can contribute to regenerative medicine research and stem cell therapies. application in the clinical setting. These challenges include the manipulation of stem cell fate pre-and post-transplantation and protection of the cells during and after their delivery to the target site. [3] The microenvironment, also referred to as stem cell niche, plays key roles in stem cell fate determination. [4] In vivo, the interplay among complex microenvironmental cues precisely regulate stem cell function so they may undergo self-renewal to maintain the stem cell pool or to undergo differentiation to regenerate tissue. However, the majority of current stem cell transplant strategies in clinical trials use injections with a buffer fluid, which provides insufficient protection and manipulation of cell fate. [5] As a result, the vast majority of transplanted cells die during their delivery or within a short time thereafter. Engineering approaches, especially in the biomaterials field, offer strategies to address the challenges and current limitations of stem cell therapy. Innovative design of biomaterials enables delicate control of their biophysical and biochemical properties, which provides an artificial niche to regulate stem cell functions. Delivery of cells via engineered biomaterial carriers can promote cell survival by reducing the microenvironmental shock (shear stress, inflammation, etc.), improving cell retention by preventing cell leakage and enhancing regenerative responses from delivered cells by manipulating stem cell fate. [6] In this review, we summarize and provide perspective on stem cell sources and the state of the art in the design, fabrication, and application of advanced functional biomaterials for stem cell delivery. We discuss current stem cell phenotypes and the requirements in biomaterial design and fabrication for successful stem cell transplantation. We also highlight recent nonclinical and clinical studies of stem cell therapy in the cardiovascular, neural, and musculoskeletal systems. Lastly, we conclude with an outlo...

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3D-engineering of Cellularized Conduits for Peripheral Nerve Regeneration

Cited by 118 publications

References 52 publications

Polymeric scaffolds for three-dimensional culture of nerve cells: a model of peripheral nerve regeneration

Polymeric scaffolds for three-dimensional culture of nerve cells: a model of peripheral nerve regeneration

3D‐engineered GelMA conduit filled with ECM promotes regeneration of peripheral nerve

Advanced Functional Biomaterials for Stem Cell Delivery in Regenerative Engineering and Medicine

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