Injectable cell‐laden hybrid bioactive scaffold containing bioactive glass microspheres

Abstract

The rising incidence of bone disorders has resulted in the need for minimally invasive therapies to meet this demand. Injectable bioactive filler, alone or with cells, could be applied in a minimally invasive manner to fulfill irregular cavities in non‐load bearing sites, which do not require high mechanical properties. Thermosensitive chitosan hydrogels that transition from a liquid to a mechanically stable solid at body temperature provide interesting features as in‐situ injectable cytocompatible biomaterials, but they are not osteoconductive. Osteoconductivity can be applied in combination with bioactive ceramics e.g., 45S5‐Bioglass® (BG). However, BG addition in chitosan hydrogels results in pH elevation, due to rapid ions release, which adversely affects gel formation, mechanical properties, and cytocompatibility. To address this, we created hybrid hydrogels, where BG is concentrated in chitosan‐based microbeads, incorporated in in‐situ gelling chitosan hydrogels. We then compared the hybrid hydrogels' properties to chitosan hydrogels with homogenously distributed BG. By varying the stirred emulsification process, BG percentage, and CH formulation, we could tune the microbeads' properties. Incorporation of BG microbeads drastically improved the hydrogel's compressive modulus in comparison to homogeneously distributed BG. It also strongly increased the survival and metabolic activities of encapsulated cells. Calcium/phosphate increase on BG microbeads suggests hydroxyapatite formation. The small diameter of microbeads allows minimally invasive injection through small needles. The feasibility of freezing and thawing microbeads provides the possibility of long‐term storage for potential clinical applications. These data indicate that this hybrid hydrogel forms a promising injectable cell‐laden bioactive biomaterial for the treatment of unloaded bone defects.

Biofabrication Strategies for Oral Soft Tissue Regeneration

“…[149] Alternatively, prefabricated multicellular building blocks such as spheroids, cell sheets, exosomes, and tissue strands are studied through scaffold-free tissue engineering. [146,150] The modular bottom-up approach replicates the microenvironment of the Culturing gingival constructs under flow using organ-on-chip system and its impact on cellular morphology and function. A) Confocal orthogonal view of the engineered tissue.…”

“…[ 149 ] Alternatively, prefabricated multicellular building blocks such as spheroids, cell sheets, exosomes, and tissue strands are studied through scaffold‐free tissue engineering. [ 146,150 ] The modular bottom‐up approach replicates the microenvironment of the tissue by allowing monodispersed cells to self‐assemble into 3D tissue with cell‐cell and cell‐matrix interactions.…”

Biodegradable electrospun poly(L‐lactide‐co‐ε‐caprolactone)/polyethylene glycol/bioactive glass composite scaffold for bone tissue engineering

“…BG has gained considerable attention in recent years, owing to its impressive array of attributes, including exceptional bioactivity, biocompatibility, biodegradability, bone‐bonding capability, and the enhanced ability to promote osseointegration and osteoconductivity. Additionally, BG exhibits low biotoxicity, further highlighting its potential for bone regeneration applications 11,12 …”

“…Additionally, BG exhibits low biotoxicity, further highlighting its potential for bone regeneration applications. 11,12 BG is usually produced through a melting process that employs nitrates as precursors. However, an enhanced bioglass can be produced using the sol-gel method, thanks to its composition.…”