Development of novel three-dimensional printed scaffolds for osteochondral regeneration - PubMed (original) (raw)

Development of novel three-dimensional printed scaffolds for osteochondral regeneration

Benjamin Holmes et al. Tissue Eng Part A. 2015 Jan.

Abstract

As modern medicine advances, various methodologies are being explored and developed in order to treat severe osteochondral defects in joints. However, it is still very challenging to cure the osteochondral defects due to their poor inherent regenerative capacity, complex stratified architecture, and disparate biomechanical properties. The objective of this study is to create novel three-dimensional (3D) printed osteochondral scaffolds with both excellent interfacial mechanical properties and biocompatibility for facilitating human bone marrow mesenchymal stem cell (MSC) growth and chondrogenic differentiation. For this purpose, we designed and 3D printed a series of innovative bi-phasic 3D models that mimic the osteochondral region of articulate joints. Our mechanical testing results showed that our bi-phasic scaffolds with key structures have enhanced mechanical characteristics in compression (a maximum Young's modulus of 31 MPa) and shear (a maximum fracture strength of 5768 N/mm(2)) when compared with homogenous designs. These results are also correlated with numerical simulation. In order to improve their biocompatibility, the scaffolds' surfaces were further modified with acetylated collagen (one of the main components in osteochondral extracellular matrix). MSC proliferation results demonstrated that incorporation of a collagen, along with biomimetically designed micro-features, can greatly enhance MSC growth after 5 days in vitro. Two weeks' chondrogenic differentiation results showed that our novel scaffolds (dubbed "key" scaffolds), both with and without surface collagen modification, displayed enhanced chondrogenesis (e.g., 130%, 114%, and 236% increases in glycosaminoglycan, type II collagen deposition, and total protein content on collagen-modified key scaffolds when compared with homogeneous controls).

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Figures

<b>FIG. 1.</b>

**FIG. 1.

A picture of our three-dimensional (3D) printer setup. Color images available online at

www.liebertpub.com/tea

<b>FIG. 2.</b>

**FIG. 2.

Computer-aided design (CAD) images of our (1) large and (2) small pore model and (A) homogeneous, (B) bi-phasic, and (C) bi-phasic key featured designs. For bi- and key scaffolds, the bone layer is on the bottom (based on the orientation of this figure) and the cartilage layer is on the top. Color images available online at

www.liebertpub.com/tea

<b>FIG. 3.</b>

**FIG. 3.

Schematic illustration of acetylated collagen linked on 3D printed bi-phasic key scaffold. Color images available online at

www.liebertpub.com/tea

<b>FIG. 4.</b>

**FIG. 4.

Images of 3D printed scaffolds with different internal geometry and pore density in mesenchymal stem cell (MSC) growth media. Small (top) and large (bottom) pore models, and (from left to right) homogeneous, bi-phasic, and bi-phasic key feature scaffolds. Color images available online at

www.liebertpub.com/tea

<b>FIG. 5.</b>

**FIG. 5.

Compressive Young's modulus data for 3D printed scaffolds. Data are±standard error of the mean, _n_=5; *p<0.05 when compared with all homogenous and bi-phasic scaffolds; **p<0.05 when compared with all other scaffolds with small features; and #p<0.05 when compared with all other scaffolds. Color images available online at

www.liebertpub.com/tea

<b>FIG. 6.</b>

**FIG. 6.

Shear fracture strength of 3D printed scaffolds, performed under wedge fracture shear testing. Data are±standard error of the mean, n_=5; ^_p<0.01 when compared with controls with intermediate pores. Color images available online at

www.liebertpub.com/tea

<b>FIG. 7.</b>

**FIG. 7.

Scanning electron microscopy images of (A, B) unmodified and (C, D) acetylated collagen-modified 3D printed osteochondral scaffolds. (E) Contact angle analysis of pure poly lactic acid (PLA) and PLA with acetylated collagen type I, showing decreased contact angle on the collagen-modified PLA. Data are±standard error of the mean, _n_=10; *p<0.05 when compared with control. Color images available online at

www.liebertpub.com/tea

<b>FIG. 8.</b>

**FIG. 8.

MSC adhesion on different 3D printed scaffolds. Data are±standard error of the mean, _n_=9; *p<0.05 when compared with control with large features and bi-phasic scaffold with small features. **p<0.05 when compared with control with large features. Color images available online at

www.liebertpub.com/tea

<b>FIG. 9.</b>

**FIG. 9.

MSC proliferation in a variety of 3D printed PLA scaffolds with different internal structure and surface modification. Data are±standard error of the mean, _n_=9; *p<0.05 when compared with all other scaffolds and **p<0.05 when compared with all scaffolds with large features and homogenous controls with small features at day 5. Color images available online at

www.liebertpub.com/tea

<b>FIG. 10.</b>

**FIG. 10.

Confocal microscopy images of MSC growing on 3D printed scaffolds after 1 and 3 days of culture. Improved cell growth and spreading morphology are observed on smaller featured scaffolds. Color images available online at

www.liebertpub.com/tea

<b>FIG. 11.</b>

**FIG. 11.

Glycosaminoglycan (GAG) synthesis in various 3D printed osteochondral scaffolds. Data are±standard error of the mean, n_=9; &p<0.05 when compared with all other scaffolds and $p<0.05 when compared with controls after 2 weeks; and ^_p<0.05 when compared with controls and bi-phasic scaffolds after 1 week. Color images available online at

www.liebertpub.com/tea

<b>FIG. 12.</b>

**FIG. 12.

Collagen type II synthesis on 3D printed scaffolds. All groups showed improvement after 2 weeks of chondrogenic differentiation. Data are±standard error of the mean, _n_=9; *p<0.05 when compared with all other scaffolds at week 1 and ^ p<0.05 when compared with all other scaffolds at week 2. Color images available online at

www.liebertpub.com/tea

<b>FIG. 13.</b>

**FIG. 13.

Total protein synthesis. Data are±standard error of the mean, n_=9; ^_p<0.05 when compared with controls, &p<0.05 when compared with all other scaffolds and &&p<0.05 when compared with bi-phasic and controls after 2 weeks. Color images available online at

www.liebertpub.com/tea

<b>FIG. 14.</b>

**FIG. 14.

A flow chart illustrating 3D printing patient-specific scaffolds with designed internal structures for osteochondral defect treatment. Color images available online at

www.liebertpub.com/tea

<b>FIG. 15.</b>

**FIG. 15.

A full knee cartilage layer CAD model and the respective 3D printed full knee construct. Color images available online at

www.liebertpub.com/tea

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