The loss of bone tissue represents a critical clinical condition that is frequently faced by surgeons. Substantial progress has been made in the area of bone research, providing insight into the biology of bone under physiological and pathological conditions, as well as tools for the stimulation of bone regeneration. The present review discusses recent advances in the field of gene-enhanced bone tissue engineering. Gene transfer strategies have emerged as highly effective tissue engineering approaches for supporting the repair of the musculoskeletal system. By contrast to treatment with recombinant proteins, genetically engineered cells can release growth factors at the site of injury over extended periods of time. Of particular interest are the expedited technologies that can be applied during a single surgical procedure in a cost-effective manner, allowing translation from bench to bedside. Several promising methods based on the intra-operative genetic manipulation of autologous cells or tissue fragments have been developed in preclinical studies. Moreover, gene therapy for bone regeneration has entered the clinical stage with clinical trials for the repair of alveolar bone. Current trends in gene-enhanced bone engineering are also discussed with respect to the movement of the field towards expedited, translational approaches. It is possible that gene-enhanced bone tissue engineering will become a clinical reality within the next few years.
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http://dx.doi.org/10.1002/jgm.3018 | DOI Listing |
ACS Biomater Sci Eng
April 2024
Department of Biomedical Engineering, University of California Irvine, Irvine, California 92697, United States.
Macrophages are innate immune cells that interact with complex extracellular matrix environments, which have varied stiffness, composition, and structure, and such interactions can lead to the modulation of cellular activity. Collagen is often used in the culture of immune cells, but the effects of substrate functionalization conditions are not typically considered. Here, we show that the solvent system used to attach collagen onto a hydrogel surface affects its surface distribution and organization, and this can modulate the responses of macrophages subsequently cultured on these surfaces in terms of their inflammatory activation and expression of adhesion and mechanosensitive molecules.
View Article and Find Full Text PDFBioact Mater
April 2022
Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China.
The complex pathogenesis of osteoporosis includes excessive bone resorption, insufficient bone formation and inadequate vascularization, a combination which is difficult to completely address with conventional therapies. Engineered exosomes carrying curative molecules show promise as alternative osteoporosis therapies, but depend on specifically-functionalized vesicles and appropriate engineering strategies. Here, we developed an exosome delivery system based on exosomes secreted by mesenchymal stem cells (MSCs) derived from human induced pluripotent stem cells (iPSCs).
View Article and Find Full Text PDFJ Diabetes Metab Disord
December 2021
Endocrinology and Metabolism Research Center (EMRC), Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
Purpose: This study aims to analyze the association between VDR gene polymorphism and the occurrence of "low bone density (LBD)/osteopenia/osteoporosis" or LBDOO in type 2 diabetes (T2D) patients among a clustered population in northwest of Iran. The studied VDR gene polymorphism included (rs7975232), (rs1544410), (rs2228570), (rs4516035) and, (rs731236).
Methods: In this population-based cross-sectional study, patients with T2D were identified within a group of 1266 participants based on self-report of diabetes, history of diabetes medication, and recorded laboratory data.
Cell Death Discov
June 2021
Research Institute for Integrative Regenerative Biomedical Engineering, Dongguk University, Goyang, 10326, Republic of Korea.
While bone has an inherent capacity to heal itself, it is very difficult to reconstitute large bone defects. Regenerative medicine, including stem cell implantation, has been studied as a novel solution to treat these conditions. However, when the local vascularity is impaired, even the transplanted cells undergo rapid necrosis before differentiating into osteoblasts and regenerating bone.
View Article and Find Full Text PDFAdv Biosyst
August 2019
Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, P. R. China.
In situ sustained release of endogenous growth factors from cells is a challenge for repair and regeneration of tissue. Although recombinant adenovirus vectors are an effective delivery system that can prolong the release of growth factors and is very suitable for the therapy of growth factors, these recombinant adenovirus vectors that are widely used at present have low safety and stability in terms of long-term expression. In this study, the above problems are solved by knocking out both E1 and E3 genes at the same time and directly inserting the gene fragments encoding target proteins after the inverted terminal repeats.
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