Applications of decellularized extracellular matrix in bone and cartilage tissue engineering

Abstract

Regenerative therapies for bone and cartilage injuries are currently unable to replicate the complex microenvironment of native tissue. There are many tissue engineering approaches attempting to address this issue through the use of synthetic materials. Although synthetic materials can be modified to simulate the mechanical and biochemical properties of the cell microenvironment, they do not mimic in full the multitude of interactions that take place within tissue. Decellularized extracellular matrix (dECM) has been established as a biomaterial that preserves a tissue's native environment, promotes cell proliferation, and provides cues for cell differentiation. The potential of dECM as a therapeutic agent is rising, but there are many limitations of dECM restricting its use. This review discusses the recent progress in the utilization of bone and cartilage dECM through applications as scaffolds, particles, and supplementary factors in bone and cartilage tissue engineering.

Keywords: bioink; bone; cartilage; decellularization; extracellular matrix; hydrogels; particles; scaffold.

Figure 1

Examining the regenerative potential of solubilized bone dECM hydrogel using ex vivo model. (a) hydrogel was loaded within the 2 mm defect site created in an embryonic Day 11 chick femur. (b) Alginate hydrogel was not incorporated into the defect site after 10 days of culture (i–ii), however alginate combined with solubilized bone dECM maintained its geometry for 10 days (iv–v). Micro‐computed tomography showed similar results (iii, vi). Reprinted from Ref. 78, Copyright 2014, with permission from Elsevier

Figure 2

Cell‐laid matrix on 3D printed PCL scaffold. (a) Expression of F‐actin of hTMSCs on PCL/PLGA scaffolds with (i) addition of ECM/TCP, (ii) addition of ECM alone, (iii) addition of TCP alone, and (iv) no additions. (b) Fluorescent micrographs of protein expression for (i) vinculin on bare‐HA scaffold, (ii) vinculin on ECM‐ornamented scaffold, (iii) actin on bare‐HA scaffold, (iv) actin on ECM‐ornamented scaffold. (a) Reprinted from Ref. 4, Copyright 2014, with permission from Elsevier. (b) Reprinted with permission from Ref. 85. Copyright 2016 Wiley Periodicals Inc

Figure 3

3D printing of bioink. Bioinks made from heart, cartilage, and adipose dECM could be 3D printed either with (cartilage, adipose) or without (heart) PCL framework to create porous scaffolds. Reprinted by permission from Macmillan Publishers Ltd: Nature Communications, Ref. 101, copyright 2014

Figure 4

Specific applications for utilizing dECM as particles. (a) Incorporating dECM on electrospun scaffold. NHS groups are introduced on the surface of electrospun poly(hydroxyalkanoate) scaffold via carbodiimide chemistry, which then acts as a binding site for dECM particles. (Insert) Scanning electron microscopy shows the presence of dECM particles (red arrows) on the surface of the scaffold. (b) Incorporating dECM for 3D printing. Decellularized bone ECM particles are mixed with PCL which results in a hybrid scaffold that is printable up to 70% bone dECM by mass. (a) Reproduced in part from Ref. 11 with permission from The Royal Society of Chemistry. (b) Reprinted with permission from Ref. 121. Copyright 2016 American Chemical Society