Review
Biochemistry & Molecular Biology
Trevor Poitras, Douglas W. Zochodne
Summary: Common mechanisms of peripheral axon regeneration are recruited following diverse forms of damage to peripheral nerve axons. Supporting peripheral axon regrowth could be achieved through direct axon support or manipulation of the inflammatory milieu. Understanding the molecular barriers to regrowth and exploiting the downstream signaling pathways that impact neuron growth are promising approaches for promoting adult peripheral axon regeneration. This review emphasizes intrinsic aspects of adult peripheral axon regeneration and highlights several molecular barriers to regrowth.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Medicine, Research & Experimental
Lingchi Kong, Xin Gao, Yun Qian, Wei Sun, Zhengwei You, Cunyi Fan
Summary: This review integrates the current understanding of the biomechanical microenvironment associated with peripheral nerve function and regeneration, introduces promising tissue engineering strategies based on biomechanical modulation, and provides suggestions and prospects for future directions.
Article
Materials Science, Biomaterials
Rinat Nigmatullin, Caroline S. Taylor, Pooja Basnett, Barbara Lukasiewicz, Alexandra Paxinou, Lorena R. Lizarraga-Valderrama, John W. Haycock, Ipsita Roy
Summary: Polyhydroxyalkanoates (PHAs) are natural, biodegradable, thermoplastic and sustainable polymers that have great potential in the fabrication of bioresorbable implantable devices for tissue engineering. This study evaluated various PHAs and synthetic aliphatic polyesters for their ability to support nerve regeneration. The results showed that one specific PHA, poly(3-hydroxyoctanoate-co-3-hydroxydecanoate), exhibited superior properties in terms of cell adhesion, cell viability, neurite extension and interaction with Schwann cells. These findings suggest that PHAs could be excellent materials for enhancing nerve regeneration and potentially used in clinical applications for peripheral nerve repair.
REGENERATIVE BIOMATERIALS
(2023)
Review
Chemistry, Multidisciplinary
Hui Zhang, Jiahui Guo, Yu Wang, Luoran Shang, Renjie Chai, Yuanjin Zhao
Summary: In recent years, artificial nerve scaffolds have emerged as a promising alternative for peripheral nerve repair. Natural polymers, with their excellent biocompatibility, low toxicity, high cell affinity, wide source, and environmental protection, are considered ideal biomaterials for tissue engineering scaffolds. The development of natural polymer-derived nerve scaffolds, combined with the integration of exogenous biomolecules, has shown great potential in enhancing nerve regeneration and functional reconstruction.
ADVANCED FUNCTIONAL MATERIALS
(2022)
Review
Biochemistry & Molecular Biology
Ben Kaplan, Shulamit Levenberg
Summary: Peripheral nerve and spinal cord injuries have significant impacts on patients' lives, with severe cases currently lacking a cure. Biomaterials can be engineered as scaffolds to mimic nerve tissue and promote axonal regeneration, as well as deliver therapeutic agents to the site of injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biotechnology & Applied Microbiology
Rebecca Powell, Despoina Eleftheriadou, Simon Kellaway, James B. Phillips
Summary: This review discusses the physical processes by which natural biomaterials mimic the function of the extracellular matrix and regulate cellular behavior, as well as highlights representative cases of controllable cell microenvironments developed through the combination of cell biology and tissue engineering principles.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Neurosciences
Yunsong Zhang, Yinying Shen, Li Zhao, Qian Zhao, Lili Zhao, Sheng Yi
Summary: Nerve injury-induced Schwann cell dedifferentiation promotes axon growth by creating a favorable microenvironment. Transcription factor BCL11A plays a crucial role in Schwann cell reprogramming during peripheral nerve regeneration. Silencing Bcl11a reduces Schwann cell viability, proliferation, migration rates, and debris clearance ability. Bcl11a deficiency leads to restricted axon elongation and myelin wrapping, resulting in failed recovery. Mechanistically, BCL11A regulates Schwann cell activity by binding to the Nr2f2 promoter and modulating Nr2f2 expression. In conclusion, BCL11A is essential for Schwann cell activation and peripheral nerve regeneration, making it a potential therapeutic target for peripheral nerve injury treatment.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yaxian Wang, Fuchao Zhang, Yunsong Zhang, Qi Shan, Wei Liu, Fengyuan Zhang, Feiyu Zhang, Sheng Yi
Summary: Research findings indicate that Btc plays essential roles in regulating Schwann cell migration and axon elongation, suggesting the potential application of Btc as a regenerative strategy for treating peripheral nerve injury.
MOLECULAR MEDICINE
(2021)
Review
Clinical Neurology
Lingmei Ni, Zhao Yao, Yifan Zhao, Tianfang Zhang, Jie Wang, Siyue Li, Zuobing Chen
Summary: Peripheral nerve injury is common in extremity trauma patients and surgical therapeutic approaches may not ensure functional recovery. Rehabilitation plays a vital role in promoting nerve repair and sensorimotor recovery through individualized electrical stimulation therapy. However, the parameters and long-term effectiveness of electrical stimulation need further exploration.
FRONTIERS IN NEUROLOGY
(2023)
Review
Biotechnology & Applied Microbiology
Jue Ling, Chang He, Shuxuan Zhang, Yahong Zhao, Meifeng Zhu, Xiaoxuan Tang, Qiaoyuan Li, Liming Xu, Yumin Yang
Summary: This article provides an overview of evaluation methods used to study scaffold-based therapies for peripheral nerve injury (PNI) in experimental animal models, with particular focus on Schwann cell functions and axonal growth within the regenerated nerve.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Review
Nanoscience & Nanotechnology
Dong-Xu Huang, Jiang-Nan Li, Ge-Yi Zhang, Wen-Gang Wang, Lei Xia, Xu Gong, Nan Zhou
Summary: Peripheral nerves have intrinsic regeneration abilities after injury, with a limit distance for spontaneous regeneration. Nerve autografts are the primary method for bridging nerve gaps, while insufficient vascularization may hinder nerve conduit bridging longer gaps. Future research could focus on enhancing angiogenesis in nerve conduits using advanced biomaterials.
SCIENCE OF ADVANCED MATERIALS
(2021)
Article
Immunology
Eri Oshima, Yoshinori Hayashi, Zhen Xie, Hitoshi Sato, Suzuro Hitomi, Ikuko Shibuta, Kentaro Urata, Junjun Ni, Koichi Iwata, Tatsuo Shirota, Masamichi Shinoda
Summary: This study aimed to identify the axon regeneration factor derived from M2 macrophages. Transcriptome analysis revealed the upregulation of the macrophage-selective lysosomal protease CTSS in the injured nerve. Macrophage ablation experiments in a rat model showed that ablation at the injured site hindered partial recovery from sensory deficits. CTSS was upregulated in the injured nerve and facilitated endogenous recovery from hypoesthesia. Additionally, CTSS promoted axon regeneration by activating Schwann cells through Ephrin-B2 shedding from fibroblasts.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Neurosciences
Chunyi Jiang, Yan Lu, Ran Zhu, Ying Zong, Yuchen Huang, Dong Wang, Zhanyun Da, Bin Yu, Longxiang Shen, Qianqian Cao
Summary: Key metabolic enzymes regulate glucose, lipid, and amino acid metabolism for cellular energy needs and also play a role in nonmetabolic signaling pathways. The role of glycometabolism in peripheral nerve axon regeneration is not well understood. This study found that the up-regulation of Pyruvate dehydrogenase beta subunit (Pdhb), a key enzyme, at the early stage of peripheral nerve injury promotes axon regeneration. Pdhb relies on lactate for energy supply and affects gene expression through histone acetylation, thereby enhancing axon regeneration.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Neurosciences
Supriya S. Wariyar, Alden D. Brown, Tina Tian, Tana S. Pottorf, Patricia J. Ward
Summary: This study investigates the impact of using fibrin glue in nerve repair on exercise-induced nerve regeneration. Results show that nerves repaired with fibrin glue exhibit more vasculature in the tissue bridge and have more robust axon regeneration after exercise compared to nerves without fibrin glue repair. When angiogenesis in the tissue bridge is prevented, exercise is unable to enhance regeneration, indicating the importance of a vascularized bridge. The combination of fibrin glue repair and exercise significantly improves vascular growth, axon elongation, neuromuscular junction reinnervation, and functional recovery.
EXPERIMENTAL NEUROLOGY
(2022)
Review
Biochemistry & Molecular Biology
Max Y. Y. Jin, Tristan E. Weaver, Adam Farris, Mayank Gupta, Alaa Abd-Elsayed
Summary: While denervation can occur with aging, peripheral nerve injuries often result in loss of function and neuropathic pain. Neuromodulation has shown promise in enhancing peripheral nerve regeneration, but additional interventions are needed to control the direction of reinnervation. More human studies are required to validate findings from animal studies and optimize neuromodulation for functional restoration.
Review
Oncology
Ruman Rahman, Miroslaw Janowski, Clare L. Killick-Cole, William G. B. Singleton, Emma Campbell, Piotr Walczak, Soumen Khatua, Lukas Faltings, Marc Symons, Julia R. Schneider, Kevin Kwan, John A. Boockvar, Steven S. Gill, J. Miguel Oliveira, Kevin Beccaria, Alexandre Carpentier, Michael Canney, Monica Pearl, Gareth J. Veal, Lisethe Meijer, David A. Walker
Summary: Brain tumors are the leading cause of cancer deaths in children and young adults, but drug treatments have had limited success due to the blood-brain barrier. This review explores techniques to enhance drug delivery to brain tumors and discusses preclinical models for translational development. It also highlights the potential of existing approved drugs when combined with efficient delivery methods. This research aims to address the current challenges faced by children with brain tumors and improve treatment outcomes.
Article
Biotechnology & Applied Microbiology
Ana L. Alves, Ana C. Carvalho, Ines Machado, Gabriela S. Diogo, Emanuel M. Fernandes, Vania I. B. Castro, Ricardo A. Pires, Jose A. Vazquez, Ricardo I. Perez-Martin, Miguel Alaminos, Rui L. Reis, Tiago H. Silva
Summary: This study evaluated the potential of Gelatin Methacryloyl (GelMA) hydrogels produced from marine-derived gelatin for corneal stromal applications. The hydrogels exhibited excellent optical and swelling properties, easy handling, structural stability, and adequate degradation rates. The addition of ascorbic acid enhanced the biological performance of the cells and induced collagen production.
BIOENGINEERING-BASEL
(2023)
Article
Materials Science, Biomaterials
Lara Pierantoni, Virginia Brancato, Joao B. Costa, Subhas C. Kundu, Rui L. Reis, Joana Silva-Correia, Joaquim M. Oliveira
Summary: A 3D breast cancer model based on collagen protein has opened up new avenues for studying cancer progression.
Article
Chemistry, Medicinal
Lingzhi Wang, Catarina Oliveira, Qiu Li, Andreia S. Ferreira, Claudia Nunes, Manuel A. Coimbra, Rui L. Reis, Albino Martins, Chunming Wang, Tiago H. Silva, Yanxian Feng
Summary: This study characterized a pharmaceutical-grade fucoidan extracted from Fucus vesiculosus and investigated its anti-inflammatory potential. The extract contained mainly fucose, followed by uronic acids, galactose, and xylose, with a molecular weight of 70 kDa and a sulfate content of around 10%. In vitro and in vivo experiments demonstrated the ability of the fucoidan extract to modulate cytokine expression and reverse inflammation induced by lipopolysaccharide.
Article
Chemistry, Physical
Andreas S. Croft, Slavko Corluka, Janine Fuhrer, Michael Woeltje, Joana Silva-Correia, Joaquim M. Oliveira, Georg F. Erbach, Rui L. Reis, Benjamin Gantenbein
Summary: Intervertebral disc herniation often causes severe pain and is associated with disc degeneration. We propose an annulus fibrosus repair approach using GG-MA and silk fibroin. The repaired discs showed no significant differences compared to the damaged discs, indicating the repair approach was successful.
Article
Nanoscience & Nanotechnology
Ane Escobar, Aleksandra Serafin, Mariana R. Carvalho, Mario Culebras, Andres Cantarero, Anne Beaucamp, Rui L. Reis, J. Miguel Oliveira, Maurice N. Collins
Summary: Novel PEDOT nanoparticles combined with silk fibroin are promising biomaterials for peripheral nerve regeneration, showing excellent mechanical and conductivity properties and avoiding scar tissue formation.
ADVANCED COMPOSITES AND HYBRID MATERIALS
(2023)
Article
Engineering, Biomedical
Luge Bai, Zhiyan Hao, Sen Wang, Jiajia Zhou, Siqi Yao, Na Pei, Hui Zhu, Kun Zhang, Rui L. Reis, J. Miguel Oliveira, Jiankang He, Dichen Li, Xinggang Mao, Ling Wang
Summary: In this study, an in vitro bioprinted 3D glioma model was proposed to simulate the natural glioma. Neurons could promote the proliferation of glioma cells and induce morphological changes in glioma cells to be neuron-like. Glioma cells, on the other hand, could maintain neuronal survival and promote neurite outgrowth.
INTERNATIONAL JOURNAL OF BIOPRINTING
(2023)
Article
Biotechnology & Applied Microbiology
Silvia Vieira, Paulina Strymecka, Luiza Stanaszek, Joana Silva-Correia, Katarzyna Drela, Michal Fiedorowicz, Izabela Malysz-Cymborska, Miroslaw Janowski, Rui Luis Reis, Barbara Lukomska, Piotr Walczak, Joaquim Miguel Oliveira
Summary: This study aims to develop a stable injectable Mn-based methacrylated gellan gum (Mn/GG-MA) hydrogel for real-time monitored cell delivery into the central nervous system. By supplementing GG-MA solutions with paramagnetic Mn2+ ions, the hydrogel can be visualized under Magnetic Resonance Imaging (MRI). Cell-laden hydrogels prepared using the Mn/GG-MA formulations remained viable after 7 days of culture. In vivo tests on immunocompromised mice showed that the injection of Mn/GG-MA solutions resulted in a continuous and traceable hydrogel visible on MRI scans. Overall, the developed formulations are suitable for non-invasive cell delivery techniques and image-guided neurointerventions.
BIOENGINEERING-BASEL
(2023)
Article
Engineering, Biomedical
Duarte Nuno Carvalho, Sophie Dani, Carmen G. Sotelo, Ricardo Perez-Martin, Rui L. Reis, Tiago H. Silva, Michael Gelinsky
Summary: Significant progress has been made in 3D printing research for tissue engineering using biomaterial inks made from natural and synthetic compounds. Marine-origin polymers have been studied as an alternative to land mammal-origin polymers, offering biocompatibility and reduced disease transmission risk. Blending collagen from shark skin, chitosan from squid pens, and fucoidan from brown algae has resulted in a printable biomaterial ink with high shape fidelity. Tests and assays have shown favorable properties and high cell viability on the 3D printed constructs.
BIOMEDICAL MATERIALS
(2023)
Review
Biotechnology & Applied Microbiology
Lara Pierantoni, Rui L. Reis, Joana Silva-Correia, Joaquim M. Oliveira, Susan Heavey
Summary: The fields of tissue bioengineering, -omics, and spatial biology offer the opportunity for a paradigm shift in breast cancer research. However, collaboration between these fields has not reached its full potential. This review discusses the latest 3D breast cancer models, their biomaterials and technological platforms, as well as their biological evaluation, highlighting the potential for better microphysiological systems, improved drug development success rates, and personalized medicine approaches.
TRENDS IN BIOTECHNOLOGY
(2023)
Article
Pharmacology & Pharmacy
Ivone M. Martins, Raphael F. Canadas, Helder Pereira, Joana Azeredo, Rui L. Reis, Joaquim M. Oliveira, Helena S. Azevedo
Summary: Osteoarthritis (OA) is a common joint disorder with limited treatment options. Researchers have identified a peptide selective for OA chondrocytes using phage display technology, which could be further developed for early diagnosis and targeted drug delivery.
ADVANCED THERAPEUTICS
(2023)
Article
Chemistry, Physical
Ivone Regina de Oliveira, Isabela dos Santos Goncalves, Kennedy Wallace dos Santos, Maria Carmo Lanca, Tania Vieira, Jorge Carvalho Silva, Ibrahim Fatih Cengiz, Rui Luis Reis, Joaquim Miguel Oliveira, Joao Paulo Miranda Ribeiro Borges
Summary: Traditional bioactive glass powders are typically composed of irregular particles that limit bone ingrowth due to low interconnectivity. Novel biocomposite macrospheres using Sr-bioactive glass, sodium alginate, polylactic acid (PLA), and chitosan (CH) as encapsulating materials were developed for bone fillers. The biocomposite macrospheres made with PLA exhibited higher porosity, interconnectivity, and protection from degradation, making them promising fillers for bone tissue repair applications.
Article
Biochemistry & Molecular Biology
Suiane Cavalcante, Sofia Viamonte, Rui S. Cadilha, Ilda P. Ribeiro, Ana Cristina Goncalves, Joao Sousa-Venancio, Marisol Gouveia, Manuel Teixeira, Mario Santos, Jose Oliveira, Fernando Ribeiro
Summary: This study aims to evaluate the effects of a single exercise bout on the circulating levels of EPCs and CECs in heart failure patients. The results showed that a single exercise bout increased the levels of EPCs but didn't change the levels of CECs. Heart failure patients had lower levels of EPCs compared to the age-matched group, but the exercise bout restored their EPCs levels to a level similar to the age-matched group.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Meeting Abstract
Cell & Tissue Engineering
Gabriela S. Diogo, Maria Permuy, Catarina F. Marques, Carmen G. Sotelo, Ricardo I. Perez Martin, Julia Serra, Pio Gonzalez, Fernando Munoz, Rogerio P. Pirraco, Rui L. Reis, Tiago H. Silva
TISSUE ENGINEERING PART A
(2023)
Meeting Abstract
Cell & Tissue Engineering
Ana Luisa Alves, Ana Cristina Carvalho, Rita O. Sousa, Catarina F. Marques, Emanuel M. Fernandes, Albino Martins, Jose A. Vasquez, Carmen G. Sotelo, Ricardo I. Perez Martin, Miguel Alaminos, Rui L. Reis, Tiago H. Silva
TISSUE ENGINEERING PART A
(2023)