Biosensors and Nanotheranostics
Bionanotechnology, Drug Delivery, Therapeutics | online ISSN 3064-7789
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Volume 4 Number 1 2025
REVIEWS (Open Access)
Advancements in Biomaterial-Based Nucleic Acid Delivery Systems for In Situ Tissue Engineering: A Systematic Review and Meta-Analysis
Md. Taufique Hasan Bhuiyan Sezan1*, Raihan Mia 2
Biosensors and Nanotheranostics 4 (1) 1-8 https://doi.org/10.25163/biosensors.4110516
Submitted: 14 September 2025 Revised: 10 November 2025 Accepted: 16 November 2025 Published: 17 November 2025
Abstract
The clinical potential of nucleic acid-based therapies in regenerative medicine is increasingly recognized, yet their translation remains limited by delivery efficiency, safety, and targeted release challenges. This systematic review and meta-analysis examine the current landscape of biomaterial-based nucleic acid delivery systems, focusing on viral and non-viral vectors integrated into scaffold platforms for in situ tissue engineering. Literature was systematically collected from peer-reviewed sources between 2009 and 2025, evaluating studies that assessed delivery efficiency, tissue-specific targeting, and therapeutic outcomes. Viral vectors, including adenovirus, adeno-associated virus (AAV), and lentivirus, demonstrated high transduction efficiency but were associated with immunogenicity and risks of insertional mutagenesis. In contrast, non-viral nanocarriers—lipid-based nanoparticles, polymeric nanoparticles, inorganic nanoparticles, and biomimetic vectors such as exosomes—exhibited enhanced biocompatibility, reduced toxicity, and customizable release profiles. Scaffold integration, including injectable hydrogels, three-dimensional porous scaffolds, and sheet-like systems, improved local retention, spatiotemporal release, and functional tissue regeneration. Meta-analysis of preclinical studies indicated significantly improved gene delivery efficiency and tissue repair outcomes when non-viral carriers were combined with tailored scaffolds (p < 0.05). However, limitations such as mechanical weakness in hydrogels, light penetration constraints, long-term bioaccumulation, and manufacturing challenges remain. This review highlights the translational potential of combining non-viral nucleic acid vectors with advanced biomaterials, offering a roadmap for clinical implementation. Addressing the identified safety and scalability challenges could accelerate the adoption of these systems for targeted, efficient, and safe regenerative therapies.
Keywords: Nucleic acid delivery, non-viral vectors, viral vectors, biomaterial scaffolds, tissue engineering, regenerative medicine, hydrogels, 3D scaffolds
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