Event Abstract

Tunable elastomeric matrices - A model system for skeletal muscle characterization

  • 1 University of Connecticut Health Center, Orthopaedic Surgery, United States
  • 2 University of Connecticut Health Center, The Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, United States
  • 3 University of Connecticut, Connecticut Institute for Clinical and Translational Science, United States

Statement of Purpose: Skeletal muscle injuries resulting from tumor resection, automobile accidents and combat injuries lead to significant muscle loss resulting in pain and loss of function, known as volumetric muscle loss (VML)[1]. The inherent healing mechanism in skeletal muscle exhibits a large deficit in regenerating VML and continues to be a significant treatment challenge[2]. In spite of the many polymer systems developed to support muscle repair and regeneration, there lacks a systematic model based on substrate stiffness and porosity to evaluate the healing mechanisms in vitro, biocompatibility and tissue compliance over the healing period. We have identified and developed a novel elastomer that allows tuning of matrix physicochemical properties by altering its monomer composition.  For instance, the ability to alter material properties in terms of stiffness, flexibility, hydrophilicity and pore properties may provide opportunities to evaluate muscle pathology and serve as a model system to study 3D tissue.

Methods: Random copolymer of polycaprolactone triol (PCL, Mn=300), succinic acid (SA) and pentaerythritol (PTN) was prepared by polycondensation reaction of varying monomer compositions (Table 1).

Table 1: Composition of synthesized random copolymers

Following heating at 180ºC for 3 hr, the resulting viscous pre-polymer was mixed with 15 wt % (dry weight of monomers) of NaCl crystals and poured into a Teflon mold for post-polymerization at 120ºC. Increasing molar ratio of PTN reduced the post-polymerization time from 6 days to 30 hr, and fixed wt % of NaCl ensured similar porosity and pore size (400-600µm) in all polymer compositions. After complete polymerization the scaffolds were repeatedly washed with deionized water to remove salts. The porous scaffolds were dried overnight and sterilized by autoclaving. The three dimensional (3D) porous elastomers were characterized for compressive strength, thermal properties, water uptake, muscle satellite cell adhesion, cell proliferation, and cytoskeletal arrangement.

Results: The novel elastomers exhibited viscoelastic and tough behavior characterized by low modulus and large elongation ratio (Fig 1). Increase in PTN content in the polymer increased the elastic modulus and functions as a modulator to control material compliance. Higher PTN content in the copolymer resulted in increased matrix hydrophilicity and improved cell adhesion. In general hydrophilic/softer substrates promoted higher human skeletal muscle satellite cell (HSkMSC) proliferation and well-spread actin stress filaments as compared to stiffer elastomers (Fig 2).

Figure 1. Representative stress-strain hysteresis curve (60% strain) showing tunability of material properties and compliance to skeletal muscle tissue

Figure 2. HSkMSC seeded on porous elastomeric scaffolds show significant cellular proliferation correlated to lower substrate stiffness (* p<0.05).

Conclusions: The mechanical and physicochemical properties of the porous elastomers were found to be compliant to passive and contracting skeletal muscle. Elastomers produced from equimoloar PTN and PCL compositions supported HSkMSC attachment, proliferation, elongation and characteristic actin filament organization found in skeletal muscle tissue phenotype. Tunability of the material and scaffold properties may serve to study 3D muscle tissue healing and disease pathology.

Funding is provided by NSF EFRI 1332329 awarded to CTL.

References:
[1] Grogan, B.F. & Hsu, J.R. Volumetric muscle loss. The Journal of the American Academy of Orthopaedic Surgeons 19 Suppl 1, S35-37 (2011).
[2] Mertens, J.P., Sugg, K.B., Lee, J.D. & Larkin, L.M. Engineering muscle constructs for the creation of functional engineered musculoskeletal tissue. Regenerative medicine 9, 89-100 (2014).

Keywords: Regenerative Medicine, 3D scaffold, mechanical property, instructive microenvironment

Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016.

Presentation Type: Poster

Topic: Biomaterials in musculoskeletal orthopeadics and tissues

Citation: James R, Kumbar SG and Laurencin CT (2016). Tunable elastomeric matrices - A model system for skeletal muscle characterization. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.01909

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Received: 27 Mar 2016; Published Online: 30 Mar 2016.