Designing a collagen-based biomaterial for multi-tissue regeneration at the tendon-bone junction
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1
University of Illinois, Chemical and Biomolecular Engineering, United States
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2
Queen Mary University of London, Biomedical Engineering and Materials, United Kingdom
Introduction: The rotator cuff is a common injury site with failure predominantly at the junction between tendon and bone. The tendon-bone junction (TBJ) displays poor healing properties even after surgical intervention, due to an inability to regenerate the interface. We are developing a collagen-glycosaminoglycan (CG) scaffold that mimics elements of the biophysical and biochemical transitions across the TBJ in vitro as a platform to spatially direct stem cell differentiation and new tissue synthesis.
Materials and Methods: Three-dimensional TBJ scaffolds were created by lyophilizing mixed suspensions of type I collagen and chondroitin sulfate with or without calcium phosphate nanocrystallites. We included geometric interdigitations between mineralized (bone) and non-mineralized (tendon) regions of the scaffold to improve scaffold tensile strength and failure, using patterned dividers to separate suspensions until immediately before lyophilization.
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Additionally, we explored inclusion of structural alignment cues via directional solidification. Multi-compartment scaffolds were comprehensively characterized through a variety of techniques (SEM, μCT, mechanical tensile testing with DIC). Finally, mesenchymal stem cells (MSCs) were cultured on scaffold variants with and without strain and characterized via fluorescent stains for functional metrics (actin production, nuclear alignment).
Results: The interfacial mechanical strength was found to increase via inclusion of an interdigitated interface and to be dependent on the angle of interdigitation. Tensile tests showed that failure load and elastic modulus increased with increasing interdigitation and decreasing tooth angle until an optimal angle was formed. Failure mode also varied between interfacial geometries. Additionally, MSCs were found to be highly sensitive to the local structural features of the tendon vs. bone compartments of the scaffold. MSCs were more aligned (nuclear and actin orientation) in scaffold variants already containing alignment cues, though tensile strain was found to further affect cell alignment.
Critically, MSCs were aligned perpendicular to strain in scaffolds without alignment cues.
Discussion: Physical stresses are concentrated across the TBJ interface, which may impact mechanical competence of a biomaterial implant. To improve tensile competence, we developed biomimetic, interdigitating geometries inspired by armored fish to create an interface between distinct non-mineralized and mineralized compartments in a single TBJ scaffold. As more teeth fit onto each sample, the angle between teeth decreased; more interfacial area is created and the interfacial strength increased. However, pattern fidelity decreased with additional interdigitations, suggesting the potential to optimize interface geometry and strength. We also describe increases in tendon-inspired cell alignment for MSCs within scaffolds containing aligned pores and under tensile load. We showed that competing strain and alignment signals produce different responses within an MSC population, suggesting that stem cells incorporate a constellation of signals into fate decisions.
Conclusion: We have shown that an interdigitated scaffold interface can increase the mechanical competence of the interface within a multi-compartment scaffold for TBJ applications. Additionally, MSCs demonstrated a greater response to structural cues than static strain. Ongoing work is looking at quantifying MSC lineage specification towards tendinous and osseous lineages across the interfacial zone as a function of both structural signals and tensile stimulation.
Keywords:
Biomimetic,
3D scaffold,
mechanical property,
bioinerface
Conference:
10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016.
Presentation Type:
New Frontier Oral
Topic:
Biomaterials for mechanical interfaces
Citation:
Mozdzen
L,
Rodgers
RC,
Screen
HR and
Harley
BA
(2016). Designing a collagen-based biomaterial for multi-tissue regeneration at the tendon-bone junction.
Front. Bioeng. Biotechnol.
Conference Abstract:
10th World Biomaterials Congress.
doi: 10.3389/conf.FBIOE.2016.01.02930
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Received:
27 Mar 2016;
Published Online:
30 Mar 2016.