Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

Abstract

The field of "regenerative medicine" (RM) was conceptually developed to aid the body's natural capacity to self-repair, a capacity which is impaired with age and in cases of disease or injury. [1] RM is a vast and multifaceted area of medicine, often microRNA-based therapies are an advantageous strategy with applications in both regenerative medicine (RM) and cancer treatments. microRNAs (miRNAs) are an evolutionary conserved class of small RNA molecules that modulate up to one third of the human nonprotein coding genome. Thus, synthetic miRNA activators and inhibitors hold immense potential to finely balance gene expression and reestablish tissue health. Ongoing industrysponsored clinical trials inspire a new miRNA therapeutics era, but progress largely relies on the development of safe and efficient delivery systems. The emerging application of biomaterial scaffolds for this purpose offers spatiotemporal control and circumvents biological and mechanical barriers that impede successful miRNA delivery. The nascent research in scaffold-mediated miRNA therapies translates know-how learnt from studies in antitumoral and genetic disorders as well as work on plasmid (p)DNA/siRNA delivery to expand the miRNA therapies arena. In this progress report, the state of the art methods of regulating miRNAs are reviewed. Relevant miRNA delivery vectors and scaffold systems applied to-date for RM and cancer treatment applications are discussed, as well as the challenges involved in their design. Overall, this progress report demonstrates the opportunity that exists for the application of miRNA-activated scaffolds in the future of RM and cancer treatments.Regenerative Medicine

Scaffold‐Based Delivery of Nucleic Acid Therapeutics for Enhanced Bone and Cartilage Repair

“…The use of RNA‐based therapeutics eliminates the requirement for nuclear entry, often regarded to be the rate‐limiting step in the delivery of pDNA‐based therapeutics, as the plasmid must enter the nucleus to gain access to the machinery required for transcription . RNA‐based therapeutics offer several exciting approaches to gene therapy as RNA molecules such as messenger (m)RNA, small interfering RNA (si)RNA, short hairpin (sh)RNA, and micro (mi)RNA are involved throughout the transcriptional, regulatory and other functional activities of the cell.…”

“…The ability to silence specific genes represents a promising therapeutic approach for various orthopedic disorders . A comprehensive review of scaffold‐based miRNA delivery in regenerative medicine was recently published by our lab . Here, in addition to highlighting scaffold‐based miRNA delivery, we also review some exciting scaffold‐based delivery approaches using siRNA for the regeneration of cartilage.…”

Therapeutic Potential of Articular Cartilage Regeneration using Tissue Engineering Based on Multiphase Designs

“…Many scaffolds have been designed to fulfill the function of miRNA delivery, mainly hydrogels, nanofibers, and porous or spongy scaffolds. Besides, the normal desired properties such as biocompatibility, easy fabrication, easy sterilization, proper mechanical properties, and adequate porosity for vessels growth, the material must retain the miRNA complexes while facilitating their sufficient exposure to the infiltrating cells without affecting its mechanical properties [68].…”

Targeting anti‐chondrogenic factors for the stimulation of chondrogenesis: A new paradigm in cartilage repair

“…PRP in particular may represent a valuable option for knee OA treatment, but the number of randomized controlled studies remains limited and the use of standard preparations is lacking. Importantly, growth factor therapy has been questioned due to the need for high dosages, that not only leads to high production costs, but also increases the risk of side effects . This can be caused by the exposure of joint tissues other than cartilage (synovium, tendons, ligaments, meniscus, subchondral bone) to the exogenous growth factors leading to synovial hyperplasia, joint inflammation and ectopic cartilage or bone formation, with pain and loss of mobility due to joint obstruction .…”

“…Importantly, growth factor therapy has been questioned due to the need for high dosages, that not only leads to high production costs, but also increases the risk of side effects. 14 This can be caused by the exposure of joint tissues other than cartilage (synovium, tendons, ligaments, meniscus, subchondral bone) to the exogenous growth factors leading to synovial hyperplasia, joint inflammation and ectopic cartilage or bone formation, with pain and loss of mobility due to joint obstruction. 15 Several studies have confirmed that repeated injections of TGF-b, Andrea BMP2, or BMP9 and adenoviral overexpression of TGF-b in murine knee joints can cause the formation of osteophytes.…”