Small molecule delivery through nanofibrous scaffolds for musculoskeletal regenerative engineering

Abstract

Musculoskeletal regenerative engineering approach using small bioactive molecules in conjunction with advanced materials has emerged as a highly promising strategy for musculoskeletal repair and regeneration. Advanced biomaterials technologies have revealed nanofiber-based scaffolds for musculoskeletal tissue engineering as vehicles for the controlled delivery of small molecule drugs. This review article highlights recent advances in nanofiber-based delivery of small molecules for musculoskeletal regenerative engineering. The article concludes with perspectives on the challenges and future directions.

MiRNA inhibition in tissue engineering and regenerative medicine

“…Even so, systemic delivery of small molecules requires repeated dosing to maintain a therapeutic but non-toxic concentration, and high biodistribution to the liver and kidneys can limit the dose. One potential strategy to optimize the local effects of small molecule miRNA inhibitors at the target site is to incorporate them into biomaterial scaffolds or other depots for local and sustained delivery [88–90]. However, local delivery of small molecules from a biomaterial scaffold may result in rapid diffusional loss of the drug away from the site of interest due to high diffusivity and permeability.…”

“…However, local delivery of small molecules from a biomaterial scaffold may result in rapid diffusional loss of the drug away from the site of interest due to high diffusivity and permeability. More advanced material approaches such as electrospinning techniques that enable encapsulation of drugs into core-sheath nanofiber scaffolds may limit this initial burst release [88]. …”

Immunomodulatory properties of stem cells and bioactive molecules for tissue engineering

“…Due to several drawbacks associated with exogenous delivery of proteins, such as high production cost, off target protein activity, and purification concerns, the utilization of small immunoregulatory molecules has emerged. The term small molecule refers to a non-protein based bioactive compound that is typically less than 1000 Da [145]. A review by Laurencin et al has examined several in vitro and in vivo studies on the effects of several small bioactive molecules in the field of bone tissue engineering [146].…”

“…The potential utility of small molecule based immunomodulation for tissue engineering is vast and has shown great promise in the field of musculoskeletal tissue engineering. Several reviews have focused on the influence these compounds have on regeneration [145][146][147][148][149]. However, the interaction between these small bioactive molecules and the immune system is only beginning to be understood.…”

Mesoporous Silica-Layered Biopolymer Hybrid Nanofibrous Scaffold: A Novel Nanobiomatrix Platform for Therapeutics Delivery and Bone Regeneration

“…[18][19][20] Along with the tailored surfaces, when scaffolds were explored to have the capacity to load and deliver bioactive molecules such as drugs and growth factors, their ability to control cells and enhance bone tissue formation significantly increases. [21][22][23][24] Not only the intrinsic properties of the scaffolds, but the exogenous factors tethered to or incorporated within the scaffolds, regulate biological pathways including recruiting stem cells, stimulating angiogenesis, and accelerating osteogenesis and mineralization. 13,25 Importantly, the bioactive molecules should be loaded safely and in sufficient quantities to stimulate 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 wanted therapeutic functions, and delivery rate of the bioactive molecules should be well controlled and sustainable to support ultimate tissue healing and bone formation.…”