A plethora of applications using polysaccharides have been developed in recent years due to their availability as well as their frequent nontoxicity and biodegradability. These polymers are usually obtained from renewable sources or are byproducts of industrial processes, thus, their use is collaborative in waste management and shows promise for an enhanced sustainable circular economy. Regarding the development of novel delivery systems for biotherapeutics, the potential of polysaccharides is attractive for the previously mentioned properties and also for the possibility of chemical modification of their structures, their ability to form matrixes of diverse architectures and mechanical properties, as well as for their ability to maintain bioactivity following incorporation of the biomolecules into the matrix. Biotherapeutics, such as proteins, growth factors, gene vectors, enzymes, hormones, DNA/RNA, and antibodies are currently in use as major therapeutics in a wide range of pathologies. In the present review, we summarize recent progress in the development of polysaccharide-based hydrogels of diverse nature, alone or in combination with other polymers or drug delivery systems, which have been implemented in the delivery of biotherapeutics in the pharmaceutical and biomedical fields.

Hydrogel-based nonviral gene delivery constitutes a powerful strategy in various regenerative medicine scenarios, as those concerning the treatment of musculoskeletal, cardiovascular, or neural tissues disorders as well as wound healing. By a minimally invasive administration, these systems can provide a spatially and temporarily defined supply of specific gene sequences into the target tissue cells that are overexpressing or silencing the original gene, which can promote natural repairing mechanisms to achieve the desired effect. In the present work, we provide an overview of the most avant-garde approaches using various hydrogels systems for controlled delivery of therapeutic nucleic acid molecules in different regenerative medicine approaches.

No abstract

Osteochondral defects involve both the articular cartilage and the underlying subchondral bone. If left untreated, they may lead to osteoarthritis. Advanced biomaterial-guided delivery of gene vectors has recently emerged as an attractive therapeutic concept for osteochondral repair. The goal of this review is to provide an overview of the variety of biomaterials employed as nonviral or viral gene carriers for osteochondral repair approaches both in vitro and in vivo, including hydrogelsPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QdWVydGFzLUJhcnRvbG9tZTwvQXV0aG9yPjxZZWFyPjIw MTg8L1llYXI+PFJlY051bT4xMTk8L1JlY051bT48RGlzcGxheVRleHQ+PHN0eWxlIHNpemU9IjEw Ij5bMV08L3N0eWxlPjwvRGlzcGxheVRleHQ+PHJlY29yZD48cmVjLW51bWJlcj4xMTk8L3JlYy1u dW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJ4NXIwYTlwdnV6MGYwMmU5 c3dkeDB2MGh0ZXBleHA5ZjlwcDkiIHRpbWVzdGFtcD0iMTU5ODgwODM4NyI+MTE5PC9rZXk+PC9m b3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBl Pjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5QdWVydGFzLUJhcnRvbG9tZSwgTS48L2F1 dGhvcj48YXV0aG9yPkJlbml0by1HYXJ6b24sIEwuPC9hdXRob3I+PGF1dGhvcj5PbG1lZGEtTG96 YW5vLCBNLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPklu c3RpdHV0ZSBvZiBQb2x5bWVyIFNjaWVuY2UgYW5kIFRlY2hub2xvZ3ktSUNUUC1DU0lDLCBDL0p1 YW4gZGUgbGEgQ2llcnZhIDMsIE1hZHJpZCwgU3BhaW4uIG1wdWVydGFzQGljdHAuY3NpYy5lcy4m I3hEO0NJQkVSLUJOTiwgSGVhbHRoIEluc3RpdHV0ZSBDYXJsb3MgSUlJLCBDL01vbmZvcnRlIGRl IExlbW9zIDMtNSwgTWFkcmlkLCBTcGFpbi4gbXB1ZXJ0YXNAaWN0cC5jc2ljLmVzLiYjeEQ7RmFj dWx0eSBvZiBNZWRpY2luZSwgVW5pdmVyc2l0eSBvZiBTYWxhbWFuY2EsIEMvQWxmb25zbyBYIGVs IFNhYmlvLCBTYWxhbWFuY2EsIFNwYWluLiYjeEQ7VW5pdmVyc2l0eSBIb3NwaXRhbCBJbmZhbnRh IEVsZW5hLCBNYWRyaWQsIFNwYWluLjwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPkluIFNp dHUgQ3Jvc3MtTGlua2FibGUgUG9seW1lciBTeXN0ZW1zIGFuZCBDb21wb3NpdGVzIGZvciBPc3Rl b2Nob25kcmFsIFJlZ2VuZXJhdGlvbjwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5BZHYgRXhwIE1l ZCBCaW9sPC9zZWNvbmRhcnktdGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+ QWR2IEV4cCBNZWQgQmlvbDwvZnVsbC10aXRsZT48L3BlcmlvZGljYWw+PHBhZ2VzPjMyNy0zNTU8 L3BhZ2VzPjx2b2x1bWU+MTA1ODwvdm9sdW1lPjxlZGl0aW9uPjIwMTgvMDQvMjU8L2VkaXRpb24+ PGtleXdvcmRzPjxrZXl3b3JkPkFuaW1hbHM8L2tleXdvcmQ+PGtleXdvcmQ+QmlvY29tcGF0aWJs ZSBNYXRlcmlhbHMvKmNoZW1pc3RyeTwva2V5d29yZD48a2V5d29yZD4qQm9uZSBSZWdlbmVyYXRp b248L2tleXdvcmQ+PGtleXdvcmQ+KkJvbmUgYW5kIEJvbmVzL2luanVyaWVzL21ldGFib2xpc20v cGF0aG9sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPipDYXJ0aWxhZ2UvaW5qdXJpZXMvbWV0YWJvbGlz bS9wYXRob2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+Q3Jvc3MtTGlua2luZyBSZWFnZW50cy8qY2hl bWlzdHJ5PC9rZXl3b3JkPjxrZXl3b3JkPkh1bWFuczwva2V5d29yZD48a2V5d29yZD5IeWRyb2dl bHMvKmNoZW1pc3RyeTwva2V5d29yZD48a2V5d29yZD5UaXNzdWUgU2NhZmZvbGRzLypjaGVtaXN0 cnk8L2tleXdvcmQ+PGtleXdvcmQ+KkJpb3BvbHltZXJzPC9rZXl3b3JkPjxrZXl3b3JkPipDb21w b3NpdGVzPC9rZXl3b3JkPjxrZXl3b3JkPipIeWRyb2dlbHM8L2tleXdvcmQ+PGtleXdvcmQ+Kklu IHNpdHUgY3Jvc3MtbGlua2luZzwva2V5d29yZD48a2V5d29yZD4qT3N0ZW9jaG9uZHJhbDwva2V5 d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4yMDE4PC95ZWFyPjwvZGF0ZXM+PGlzYm4+MDA2 NS0yNTk4IChQcmludCkmI3hEOzAwNjUtMjU5OCAoTGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1u dW0+Mjk2OTE4Mjk8L2FjY2Vzc2lvbi1udW0+PHVybHM+PHJlbGF0ZWQtdXJscz48dXJsPmh0dHBz Oi8vd3d3Lm5jYmkubmxtLm5paC5nb3YvcHVibWVkLzI5NjkxODI5PC91cmw+PC9yZWxhdGVkLXVy bHM+PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMDA3Lzk3OC0zLTMxOS03Njcx MS02XzE1PC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48L3JlY29yZD48L0NpdGU+PC9FbmROb3Rl Pn== PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QdWVydGFzLUJhcnRvbG9tZTwvQXV0aG9yPjxZZWFyPjIw MTg8L1llYXI+PFJlY051bT4xMTk8L1JlY051bT48RGlzcGxheVRleHQ+PHN0eWxlIHNpemU9IjEw Ij5bMV08L3N0eWxlPjwvRGlzcGxheVRleHQ+PHJlY29yZD48cmVjLW51bWJlcj4xMTk8L3JlYy1u dW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJ4NXIwYTlwdnV6MGYwMmU5 c3dkeDB2MGh0ZXBleHA5ZjlwcDkiIHRpbWVzdGFtcD0iMTU5ODgwODM4NyI+MTE5PC9rZXk+PC9m b3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBl Pjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5QdWVydGFzLUJhcnRvbG9tZSwgTS48L2F1 dGhvcj48YXV0aG9yPkJlbml0by1HYXJ6b24sIEwuPC9hdXRob3I+PGF1dGhvcj5PbG1lZGEtTG96 YW5vLCBNLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPklu c3RpdHV0ZSBvZiBQb2x5bWVyIFNjaWVuY2UgYW5kIFRlY2hub2xvZ3ktSUNUUC1DU0lDLCBDL0p1 YW4gZGUgbGEgQ2llcnZhIDMsIE1hZHJpZCwgU3BhaW4uIG1wdWVydGFzQGljdHAuY3NpYy5lcy4m I3hEO0NJQkVSLUJOTiwgSGVhbHRoIEluc3RpdHV0ZSBDYXJsb3MgSUlJLCBDL01vbmZvcnRlIGRl IExlbW9zIDMtNSwgTWFkcmlkLCBTcGFpbi4gbXB1ZXJ0YXNAaWN0cC5jc2ljLmVzLiYjeEQ7RmFj dWx0eSBvZiBNZWRpY2luZSwgVW5pdmVyc2l0eSBvZiBTYWxhbWFuY2EsIEMvQWxmb25zbyBYIGVs IFNhYmlvLCBTYWxhbWFuY2EsIFNwYWluLiYjeEQ7VW5pdmVyc2l0eSBIb3NwaXRhbCBJbmZhbnRh IEVsZW5hLCBNYWRyaWQsIFNwYWluLjwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPkluIFNp dHUgQ3Jvc3MtTGlua2FibGUgUG9seW1lciBTeXN0ZW1zIGFuZCBDb21wb3NpdGVzIGZvciBPc3Rl b2Nob25kcmFsIFJlZ2VuZXJhdGlvbjwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5BZHYgRXhwIE1l ZCBCaW9sPC9zZWNvbmRhcnktdGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+ QWR2IEV4cCBNZWQgQmlvbDwvZnVsbC10aXRsZT48L3BlcmlvZGljYWw+PHBhZ2VzPjMyNy0zNTU8 L3BhZ2VzPjx2b2x1bWU+MTA1ODwvdm9sdW1lPjxlZGl0aW9uPjIwMTgvMDQvMjU8L2VkaXRpb24+ PGtleXdvcmRzPjxrZXl3b3JkPkFuaW1hbHM8L2tleXdvcmQ+PGtleXdvcmQ+QmlvY29tcGF0aWJs ZSBNYXRlcmlhbHMvKmNoZW1pc3RyeTwva2V5d29yZD48a2V5d29yZD4qQm9uZSBSZWdlbmVyYXRp b248L2tleXdvcmQ+PGtleXdvcmQ+KkJvbmUgYW5kIEJvbmVzL2luanVyaWVzL21ldGFib2xpc20v cGF0aG9sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPipDYXJ0aWxhZ2UvaW5qdXJpZXMvbWV0YWJvbGlz bS9wYXRob2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+Q3Jvc3MtTGlua2luZyBSZWFnZW50cy8qY2hl bWlzdHJ5PC9rZXl3b3JkPjxrZXl3b3JkPkh1bWFuczwva2V5d29yZD48a2V5d29yZD5IeWRyb2dl bHMvKmNoZW1pc3RyeTwva2V5d29yZD48a2V5d29yZD5UaXNzdWUgU2NhZmZvbGRzLypjaGVtaXN0 cnk8L2tleXdvcmQ+PGtleXdvcmQ+KkJpb3BvbHltZXJzPC9rZXl3b3JkPjxrZXl3b3JkPipDb21w b3NpdGVzPC9rZXl3b3JkPjxrZXl3b3JkPipIeWRyb2dlbHM8L2tleXdvcmQ+PGtleXdvcmQ+Kklu IHNpdHUgY3Jvc3MtbGlua2luZzwva2V5d29yZD48a2V5d29yZD4qT3N0ZW9jaG9uZHJhbDwva2V5 d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4yMDE4PC95ZWFyPjwvZGF0ZXM+PGlzYm4+MDA2 NS0yNTk4IChQcmludCkmI3hEOzAwNjUtMjU5OCAoTGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1u dW0+Mjk2OTE4Mjk8L2FjY2Vzc2lvbi1udW0+PHVybHM+PHJlbGF0ZWQtdXJscz48dXJsPmh0dHBz Oi8vd3d3Lm5jYmkubmxtLm5paC5nb3YvcHVibWVkLzI5NjkxODI5PC91cmw+PC9yZWxhdGVkLXVy bHM+PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMDA3Lzk3OC0zLTMxOS03Njcx MS02XzE1PC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48L3JlY29yZD48L0NpdGU+PC9FbmROb3Rl Pn== , solid scaffolds, and hybrid materials. The data show that a site-specific delivery of therapeutic gene vectors in the context of acellular or cellular strategies allows for a spatial and temporal control of osteochondral neotissue composition in vitro. In vivo, implantation of acellular hydrogels loaded with nonviral or viral vectors has been reported to significantly improve osteochondral repair in translational defect models. These advances support the concept of scaffold-mediated gene delivery for osteochondral repair.

Gene transfer to mesenchymal stem cells constitutes a powerful approach to promote their differentiation into the appropriate cartilage phenotype. Although viral vectors represent gold standard vehicles, because of their high efficiency, their use is precluded by important concerns including an elevated immunogenicity and the possibility of insertional mutagenesis. Therefore, the development of new and efficient non-viral vectors is under active investigation. In the present study, we developed new non-viral carriers based on niosomes to promote the effective chondrogenesis of human MSCs. Two different niosome formulations were prepared by varying their composition on non-ionic surfactant, polysorbate 80 solely (P80), or combined with poloxamer 407 (P80PX). The best niosome formulation was proven to transfer a plasmid, encoding for the potent chondrogenic transcription factor SOX9 in hMSC aggregate cultures. Transfection of hMSC aggregates via nioplexes resulted in an increased chondrogenic differentiation with reduced hypertrophy. These results highlight the potential of niosome formulations for gene therapy approaches focused on cartilage repair.