Tissue Regeneration through Cyber‐Physical Systems and Microbots

Abstract

Tissue engineering is a systematic approach of assembling cells onto a 3D scaffold to form a functional tissue in the presence of critical growth factors. The scaffolding system guides stem cells through topological, physiochemical, and mechanical cues to differentiate and integrate to form a functional tissue. However, cellular communication during tissue formation taking place in a reactor needs to be understood properly to enable appropriate positioning of the cells in a 3D environment. Hence, sensors and actuators integrated with cyber‐physical system (CPS) may be able to sense the tissue microenvironment and direct cells/cellular aggregates to an appropriate position, respectively. This can facilitate better cell‐to‐cell communication and cell–extracellular matrix communication for proper tissue morphogenesis. Advancements are made in the field of smart scaffolds that can morph cells/cellular aggregates after sensing the cellular microenvironment in a desired 3D architecture by providing appropriate cues. Recent scientific developments in the additive manufacturing technology have enabled the fabrication of smart scaffolds to create structural and functional tissue constructs. Sensors/actuators, cyber‐systems, smart materials, and additive manufacturing put together is expected to lead to improved tissue‐engineered medical products. The present review aims to highlight the possibilities of advancement of BioCPS for tissue engineering and regenerative medicine.

Ligand Coupling and Decoupling Modulates Stem Cell Fate

“…These findings suggest that the remote control of ligandcoupling is cytocompatible and temporally regulates focal adhesion and mechanosensing-mediated potential differentiation of stem cells in vivo, thereby presenting bright prospects for novel dynamic regenerative therapies. [80,81] Approval (KOREA-2021-0006) was obtained from the Institutional Animal Care and Use Committee of Korea University prior to the surgery.…”

Modulation of Macrophages by In Situ Ligand Bridging

“…Our dynamic manipulation of RGD bridging can elucidate the dynamics of host macrophages interacting with ECM proteins that regulate the integrin receptor recruitment-dependent pro-healing tissue regeneration. [62,63]…”

Engineering biomaterials to 3D-print scaffolds for bone regeneration: practical and theoretical consideration

“…[46][47][48] The fluid flow through these scaffolds also causes shear stress known as wall shear stress (WSS), which again acts as a mechanical stimulus. 49 Studies have revealed that the fluid properties, such as velocity and viscosity, affect the cell attachment and proliferation. For example, a scaffold surface subjected to higher WSS under accelerated fluid flow may damage cell attachment, while slow fluid flow may be not sufficient to generate the mechanical stimuli that affect cell proliferation and differentiation.…”

“…The use of smart materials that can be employed for designing scaffolds using AM technologies can help in sensing, and simultaneous responding to the cellular microenvironment during tissue development is becoming a reality. 49 With the proper selection of infiltrated material and incorporation of complex and load-bearing geometrical design, hybrid composites of polymers, bioceramics and degradable metals could be the next generation material of choice over the established metallic bone plates, which have the major drawback of a second surgery for the removal of these metallic bio implants. The hybrid composite contains calcium and phosphate ions (known for their osteointegration abilities), which further promotes bone ingrowth.…”