Review on Computer-Aided Design and Manufacturing of Drug Delivery Scaffolds for Cell Guidance and Tissue Regeneration

Abstract

In the last decade, additive manufacturing (AM) processes have updated the fields of biomaterials science and drug delivery as they promise to realize bioengineered multifunctional devices and implantable tissue engineering (TE) scaffolds virtually designed by using computer-aided design (CAD) models. However, the current technological gap between virtual scaffold design and practical AM processes makes it still challenging to realize scaffolds capable of encoding all structural and cell regulatory functions of the native extracellular matrix (ECM) of health and diseased tissues. Indeed, engineering porous scaffolds capable of sequestering and presenting even a complex array of biochemical and biophysical signals in a time- and space-regulated manner, require advanced automated platforms suitable of processing simultaneously biomaterials, cells, and biomolecules at nanometric-size scale. The aim of this work was to review the recent scientific literature about AM fabrication of drug delivery scaffolds for TE. This review focused on bioactive molecule loading into three-dimensional (3D) porous scaffolds, and their release effects on cell fate and tissue growth. We reviewed CAD-based strategies, such as bioprinting, to achieve passive and stimuli-responsive drug delivery scaffolds for TE and cancer precision medicine. Finally, we describe the authors’ perspective regarding the next generation of CAD techniques and the advantages of AM, microfluidic, and soft lithography integration for enhancing 3D porous scaffold bioactivation toward functional bioengineered tissues and organs.

Review on Bioinspired Design of ECM-Mimicking Scaffolds by Computer-Aided Assembly of Cell-Free and Cell Laden Micro-Modules

“…Magnetically activated scaffolds were recently fabricated to promote in vivo vascular recovery by macrophages recruiting, followed by the proliferation of mouse aortic vascular smooth muscle cells and rapid reendothelialization [ 73 ]. Light is a non-invasive stimulus that enabled high spatial resolution and the temporal control of drug release [ 17 ]. 3D printed hydrogel patches decorated with photoactive and antibacterial tetrapodal zinc oxide microparticles were developed as light-activated scaffolds for wound healing [ 74 ].…”

“…In fact, these techniques enabled the design and manufacture of porous implantable scaffolds characterized by patient-specific size, shape and geometrical features, reliable microstructural properties, and controlled biomechanical response [ 2 , 3 , 12 , 13 ]. The regenerative potential of these scaffolds was considerably improved by integrating mechanisms of loading and controlled delivery of tissue morphogenic and tissue modulator molecules, such as growth factors (GFs) [ 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. For instance, bioprinted drug delivery scaffolds were developed for applications such as the reconstruction of nucleus pulposus and annulus fibrosus of the intervertebral disc [ 21 ] and the repair of the regional architecture of osteochondral tissue [ 22 ].…”

Electrospun self-emulsifying core-shell nanofibers for effective delivery of paclitaxel

“…However, the number of drug candidates with low solubility and high permeability (BCS Class II medicines) is always increasing, and the high water-soluble and permeable drug candidates occupy only 8% in pharmaceutical industry ( Ortega et al, 2020 ; Köse et al, 2021 ; Ning et al, 2021 ; Chen et al, 2022a ; Yu and Zhao, 2022 ). Thereby, the poor solubility of drugs pose a long-existing and difficult challenge to the researchers in the fields of pharmaceutics, bioengineering and biotechnology ( Butreddy et al, 2021 ; Cai et al, 2021 ; Feng and Hao, 2021 ; Salerno and Netti, 2021 ; Sultana et al, 2021 ; Obeidat and Al-Natour, 2022 ). Many “top-down” and “bottom-up” nano fabrication methods have been exploited to provide solutions for this issue ( Esim and Hascicek, 2021 ; Tabakoglu et al, 2022 ; Tang et al, 2022a ; Vega-Vásquez et al, 2020 ).…”

Enhancing Stem Cell-Based Therapeutic Potential by Combining Various Bioengineering Technologies

“…The biomaterial scaffold-based approaches are primarily designed to incorporate living therapeutic cells within a porous 3D scaffold and signaling molecules or growth factors by providing a tissue architecture for cell infiltration and proliferation to promote the repair and regeneration of damaged tissue ( Salerno and Netti, 2021 ). For example, the combination of several biodegradable 3D scaffolds and transplanted stem cells is an attractive therapeutic strategy for the regenerations of injured tissues by facilitating cell survival and retention ( Abbott et al, 2012 ; Dash et al, 2018 ; Nagano et al, 2021 ).…”