High-Throughput Production of Microsponges from Platelet Lysate for Tissue Engineering Applications

Abstract

Cell-based therapies require a large number of cells, as well as appropriate methods to deliver the cells to damaged tissue. Microcarriers provide an optimal platform for large scale cell culture while also improving cell retention during cell delivery. However, this technology still presents significant challenges due to low throughput fabrication methods and an inability of the microcarriers to recreate the properties of human tissue. This work proposes, for the first time, the use of methacryloyl platelet lysates (PLMA), a photocrosslinkable material derived from human platelet lysates, to produce porous microcarriers. Initially, high quantities of PLMA/alginate core-shell microcapsules are produced using coaxial electrospray. Subsequently, the microcapsules are collected, irradiated with UV light, washed, and freeze-dried yielding PLMA microsponges. These microsponges are able to support the adhesion and proliferation of human adipose-derived stem cells (hASCs), while also displaying potential in the assembly of autologous microtissues. Cell-laden microsponges were shown to self-organize into aggregates, suggesting possible applications in bottom-up tissue engineering applications.

Self‐Assembly of Platelet Lysates Proteins into Microparticles by Unnatural Disulfide Bonds for Bottom‐Up Tissue Engineering

“…This emphasizes the role Cys residues in the formation of PL microparticle via formation of unnatural disulfide bonds. Unlike alternative techniques that require accounting for surface charges or chemical engineering to produce protein-based microparticles, [23,24] using the redox behavior of cysteine residues can facilitate the assembly of a complex mixture of proteins into microparticles.…”

“…[ 23 ] Recently, researchers showed the ability to use a complex mixture of proteins from human‐derived platelet lysates (PLs) using photo‐crosslinking of previously inserted chemical motifs and electrospray to fabricate sponge‐like microparticles. [ 24 ] A simple approach using silk‐elastin‐like recombiners revealed the possibility to self‐assemble these proteins into morphologically rich microparticles based on their ability to interact intra‐ and intermolecularly via non‐covalent interactions. [ 25 ] Tertiary and quaternary structures of proteins are primarily guided by non‐covalent and covalent interactions.…”

Bioactive Nanocomposite Microsponges for Effective Reconstruction of Critical-Sized Calvarial Defects in Rat Model

“…On day 7, the rBMSCs extended more filopodia and connected nearby microsponges together, resulting in self-assembled cell–microsponge aggregates ( Figure 5B ), in line with the concept of bottom-up organization. 38 These results indicate that the CS-HAP microsponges are suitable for cell attachment and proliferation when transplanted to bone defects.

Figure 5 Cell attachment, proliferation, and morphology.

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3D printing of cell-delivery scaffolds for tissue regeneration

“…In order to fabricate ideal cell-delivery scaffolds, various manufacture methods, such as lyophilization, electrospinning and 3D printing, have been applied to imitating the tissue structure [ 10–13 ]. Among these methods, 3D printing has attracted a lot of attention due to its advantages in imitating the 3D structure of target tissue.…”