Crosslinking strategies of decellularized extracellular matrix in tissue regeneration

Abstract

By removing the immunogenic cellular components through various decellularization methods, decellularized extracellular matrix (dECM) is considered a promising material in the field of tissue engineering and regenerative medicine with highly preserved physicochemical properties and superior biocompatibility. However, decellularization treatment can lead to some loss of structural integrity, mechanical strength, degradation stability, and biological performance of dECM biomaterials. Therefore, physical and chemical crosslinking methods are preferred to restore or even improve the biomechanical properties, stability, and bioactivity, and to achieve a delicate balance between degradation of the implanted biomaterial and regeneration of the host tissue. This review provides an overview of dECM biomaterials, and describes and compares the mechanisms and characteristics of commonly used crosslinking methods for dECM, with a focus on the potential applications of versatile dECM‐based biomaterials derived from skin, cardiac tissues (pericardium, heart valves, myocardial tissue), blood vessels, liver, and kidney, modified with different chemical crosslinking reagents, in tissue and organ regeneration.

Regulatory effects of stress release from decellularized periosteum on proliferation, migration, and osteogenic differentiation of periosteum-derived cells

“…21 To address these challenges, cross-linking treatments have been shown to be effective in restoring or even improving the mechanical strength, chemical stability and biological properties of decellularized matrices. 22 3.1.2. Mechanical properties and microstructure of decellularized periosteum.…”

Extracellular matrix-derived materials for tissue engineering and regenerative medicine: A journey from isolation to characterization and application

“…The required additional processing steps can be detrimental to the biocompatibility of the final scaffold since they usually involve chemical modifications that impact properties of the biomaterials other than the mechanical. Reagents such as glutaraldehyde have excellent crosslinking efficiency but have been shown to induce cytotoxic effects in vitro and in vivo [ 297 ]. Therefore, the search for crosslinkers that are efficient without impacting the biocompatibility of the biomaterial is and will be an essential topic for the widespread application of ECM-derived biomaterials in TERM applications.…”

“…Therefore, the search for crosslinkers that are efficient without impacting the biocompatibility of the biomaterial is and will be an essential topic for the widespread application of ECM-derived biomaterials in TERM applications. The use of natural compounds derived from plants such as genipin or poliphenols as crosslinkers has shown to be promising in that regard [ 216 , 297 ] and therefore we believe that other natural compounds derived from earth or sea organisms [ 297 , 298 ] may be part of the solution for the crosslinking problem.…”

Engineering cell-derived extracellular matrix for peripheral nerve regeneration

“…EDC mainly activates carboxyl groups, which react with free amino groups to form amide bonds. EDC is very efficient in crosslinking ECMs and optimizing their mechanical properties [ 207 ]. However, the physical stability of EDC-crosslinked biomaterials is weaker than that of glutaraldehyde-crosslinked biomaterials due to the weak capacity of EDC for crosslinking distal protein molecules [ 197 ].…”