Co-electrospun dual scaffolding system with potential for muscle-tendon junction tissue engineering.

Tissue engineering has had successes developing single tissue types, but there is a need for methods that will allow development of composite tissues. For instance, muscle-tendon junctions (MTJ) require a seamless interface to allow force transfer from muscle to tendon. One challenge in engineering MTJs is designing a continuous scaffold suitable for both tissue types. We aimed to create a dual scaffold that exhibits regional mechanical property differences that mimic the trends seen in native MTJ. Poly(ε-caprolactone)/collagen and poly(l-lactide)/collagen were co-electrospun onto opposite ends of a mandrel to create a scaffold with 3 regions. Scaffolds were characterized with scanning electron microscopy, tensile testing (uniaxial, cyclic, and video strain), for cytocompatibility using MTS, and seeded with C2C12 myoblasts and NIH3T3 fibroblasts. Native porcine diaphragm MTJs were also analyzed with video strain for comparison. Integrated scaffolds were created with fiber diameters from 452-549 nm. Scaffolds exhibited regional variations in mechanical properties with moduli from 4.490-27.62 MPa and generally withstood cyclic testing, although with hysteresis. Video analysis showed scaffold strain profiles exhibited similar trends to native MTJ. The scaffolds were cytocompatible and accommodated cell attachment and myotube formation. The properties engineered into these scaffolds make them attractive candidates for tissue engineering of MTJs.

[1]  Aladin M Boriek,et al.  Passive mechanics of muscle tendinous junction of canine diaphragm. , 2005, Journal of applied physiology.

[2]  Ross A. Marklein,et al.  The potential to improve cell infiltration in composite fiber-aligned electrospun scaffolds by the selective removal of sacrificial fibers. , 2008, Biomaterials.

[3]  Ellen M Arruda,et al.  Structure and functional evaluation of tendon-skeletal muscle constructs engineered in vitro. , 2006, Tissue engineering.

[4]  W E Garrett,et al.  The influence of strain rate on the passive and stimulated engineering stress--large strain behavior of the rabbit tibialis anterior muscle. , 1998, Journal of biomechanical engineering.

[5]  G. Borschel,et al.  Contractile Skeletal Muscle Tissue-Engineered on an Acellular Scaffold , 2004, Plastic and reconstructive surgery.

[6]  M. Harmsen,et al.  Current opportunities and challenges in skeletal muscle tissue engineering , 2009, Journal of tissue engineering and regenerative medicine.

[7]  J. Goh,et al.  Characterization of a novel polymeric scaffold for potential application in tendon/ligament tissue engineering. , 2006, Tissue engineering.

[8]  Robert L Sah,et al.  The impact of biomechanics in tissue engineering and regenerative medicine. , 2009, Tissue engineering. Part B, Reviews.

[9]  Donald E Ingber,et al.  Tensegrity and mechanotransduction. , 2008, Journal of bodywork and movement therapies.

[10]  Giulio Cossu,et al.  Electrospun degradable polyesterurethane membranes: potential scaffolds for skeletal muscle tissue engineering. , 2005, Biomaterials.

[11]  Anthony Atala,et al.  Tissue Engineering a Complete Vaginal Replacement From a Small Biopsy of Autologous Tissue , 2008, Transplantation.

[12]  Zi Yin,et al.  The regulation of tendon stem cell differentiation by the alignment of nanofibers. , 2010, Biomaterials.

[13]  Donald E. Ingber,et al.  Tensegrity-based mechanosensing from macro to micro. , 2008, Progress in biophysics and molecular biology.

[14]  R. A. Murphy,et al.  Mechanical properties of the cat soleus muscle in situ. , 1974, The American journal of physiology.

[15]  Michael S Sacks,et al.  Tissue-to-cellular level deformation coupling in cell micro-integrated elastomeric scaffolds. , 2008, Biomaterials.

[16]  Kathleen A Derwin,et al.  Mechanical conditioning of cell-seeded small intestine submucosa: a potential tissue-engineering strategy for tendon repair. , 2007, Tissue engineering.

[17]  Adam J. Engler,et al.  Myotubes differentiate optimally on substrates with tissue-like stiffness , 2004, The Journal of cell biology.

[18]  Bin Wang,et al.  Engineering of extensor tendon complex by an ex vivo approach. , 2008, Biomaterials.

[19]  William R Wagner,et al.  Fabrication of biodegradable elastomeric scaffolds with sub-micron morphologies. , 2004, Journal of biomedical materials research. Part A.

[20]  G. Beaupré,et al.  Mechanical properties of the human achilles tendon. , 2001, Clinical biomechanics.

[21]  James J. Yoo,et al.  Tissue-engineered autologous bladders for patients needing cystoplasty , 2006, The Lancet.

[22]  Joseph D. Bronzino,et al.  The Biomedical Engineering Handbook , 1995 .

[23]  Joel D Stitzel,et al.  Cyclic mechanical preconditioning improves engineered muscle contraction. , 2008, Tissue engineering. Part A.

[24]  Anthony Atala,et al.  Development of a composite vascular scaffolding system that withstands physiological vascular conditions. , 2008, Biomaterials.

[25]  Joe Tien,et al.  Mechanotransduction at cell-matrix and cell-cell contacts. , 2004, Annual review of biomedical engineering.

[26]  Anthony Atala,et al.  In vitro evaluation of electrospun nanofiber scaffolds for vascular graft application. , 2007, Journal of biomedical materials research. Part A.

[27]  V. Edgerton,et al.  Predictability of skeletal muscle tension from architectural determinations in guinea pig hindlimbs. , 1984, Journal of applied physiology: respiratory, environmental and exercise physiology.

[28]  Johnna S Temenoff,et al.  Engineering orthopedic tissue interfaces. , 2009, Tissue engineering. Part B, Reviews.

[29]  Z. Yablonka-Reuveni,et al.  The Skeletal Muscle Satellite Cell: The Stem Cell That Came in From the Cold , 2006, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[30]  J. Trotter.  Structure-function considerations of muscle-tendon junctions. , 2002, Comparative biochemistry and physiology. Part A, Molecular & integrative physiology.

[31]  George J Christ,et al.  The influence of electrospun aligned poly(epsilon-caprolactone)/collagen nanofiber meshes on the formation of self-aligned skeletal muscle myotubes. , 2008, Biomaterials.

[32]  Yilin Cao,et al.  Bridging tendon defects using autologous tenocyte engineered tendon in a hen model. , 2002, Plastic and reconstructive surgery.

[33]  M. Khil,et al.  An improved hydrophilicity via electrospinning for enhanced cell attachment and proliferation. , 2006, Journal of biomedical materials research. Part B, Applied biomaterials.

[34]  R. Shadwick,et al.  Relationship between body mass and biomechanical properties of limb tendons in adult mammals. , 1994, The American journal of physiology.

[35]  Karl Grosh,et al.  Engineering of functional tendon. , 2004, Tissue engineering.

[36]  Younan Xia,et al.  Nanofiber scaffolds with gradations in mineral content for mimicking the tendon-to-bone insertion site. , 2009, Nano letters.

[37]  Yimin Zhao,et al.  Clinical transplantation of a tissue-engineered airway , 2009, The Lancet.

[38]  Marcin Maruszewski,et al.  Effectiveness of haemodialysis access with an autologous tissue-engineered vascular graft: a multicentre cohort study , 2009, The Lancet.

[39]  E. Zussman,et al.  One-step production of polymeric microtubes by co-electrospinning. , 2007, Small.