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Biodurable Reticulated Elastomeric Matrix as Scaffolds for Tissue Engineering

Craig Friedman, Yong Song, Arindam Datta, Lawrence Lavelle, and Rujul Majmundar. Biomerix Corporation, 41 West 57th Street, New York, NY 10019

Introduction:  A suitable matrix for tissue engineering (TE) scaffold is a biocompatible material that allows for attachment, growth and proliferation of cells to regenerate new tissues for repair of chronic wounds 1,2. Two areas that could benefit from using TE scaffolds with appropriate functionalities are the reconstruction of chronic rotator cuff (RC) tears that are associated with high rates of failure and the repair of various hernias in the abdominal walls with reduced complications 3,4.   The primary goal of both repairs is adequate initial strength of fixation to allow appropriate rehabilitation while the reparative process and eventual repair, reattachment and integration of the damaged or weakened tissue is completed. 

In case of chronic RC tears, sometimes the defect persists as the tear cannot be completely repaired to its bony insertion and the common mode of failure of the suture tendon construct, which is normally repaired by sutures and suture anchors, can be attributed to poor biology and biomechanics of the compromised musculotendinous unit. It is believed that augmentation of such a defect with appropriate scaffold material will allow tissue ingrowth and reorganization leading to better integration of tendon and mineralized tissue and possibly reduced re-tear rates.  In case of hernia, complaints such as seromas, deceased abdominal mobility and adhesion are known to occur even when the current meshes provide adequate mechanical support for resisting intra-abdominal pressures.  It is believed that flexible scaffolds that will allow for higher tissue ingrowth and improved biointegration will be able to alleviate the situation5

The objective of the study is to investigate whether the use of an appropriate biocompatible TE scaffold in the augmentation of a chronic RC tendon or the repair of an abdominal hernia will result in tissue ingrowth, exhibit favorable histology and increase biomechanical strength of the healed tissue.

Materials and Methods:  The scaffold used in these repairs comprises a matrix that is a crosslinked polycarbonate polyurethane-urea.  The matrix is biodurable and elastomeric with a reticulated morphology consisting of an open celled, porous structure with an interconnected network of cells and pores.  The network of cells forms a 3-dimensional spatial structure or void phase, which is interconnected via the open pores that provide connectivity between the cells.  It has a large void content around 95%, which together with its reticulated morphology permits a high degree of cellular proliferation and tissue ingrowth throughout the porous scaffold.  The matrix is biostable resisting degradation in hydrolytic, enzymatic and oxidative environments.  1-D fibers or 2-D meshes can be used to reinforce the matrix to enhance its mechanical performance, if necessary, when used as a surgical mesh for reconstructive surgery.

In the first study, chronic defects were created by detaching the infraspinatus tendons from the humerus in twenty-four skeletally mature female sheep weighing 60 to 100 Kg.  The tendons were reattached to the humerus using a suture/anchoring technique mimicking a traditional RC repair.  In 12 sheep, 2mm thickness patches of the matrix (containing a grid of PET sutures) were augmented on top of the repaired site by the use of sutures and anchors.  In the remaining 12 sheep, reattachment was performed with no augmentation.  All animals were sacrificed after 12 weeks and analyzed for histology and biomechanical testing.

In the second study, host tissue response was studied by placing patches (measuring 1 cm x 1 cm in size) of the matrix to repair defects (hernias) in the abdominal wall of rats.  The defect left part of the abdominal fascia and the peritoneum intact, removing all layers of the internal and external abdominal oblique muscles.  The test article was then implanted to replace the excised muscle and was surrounded by native muscle tissue, subcutaneous tissue, and fascia.  Each implant group consisted of 4 rats and which were sacrificed at various intervals up to 16 weeks.

Results and Discussion:  The properties of the matrix are as follows: density is 0.056gm/cc; average cell sizes are 300 to 400 μm; tensile strength is 0.35 MPa; elongation to break > 175 %; tensile modulus is 0.20 Mpa; compression strength @ 50% strain is 0.01 MPa; Darcy permeability is greater than 500 (compared to under 10 for unreticulated porous foam of same density); and the material recovers to 90% of the original height in less than 80 seconds after being compressed at 50% strain for 2 hours.

For the sheep study, the ultimate force and ultimate stress for the augmented shoulders were 1328±427 N and 4.2±2.3 MPa compared to 762±474 N and 2.1±1.4 MPa for the shoulders without scaffold augmentation, demonstrating that both ultimate force and stress were significantly greater for the shoulders repaired with the use of a TE scaffold patch.  Histological evaluation (H&E stained) showed that the patch supported tissue ingrowth (Fig. 1) along with tendon healing and repair.  The bone tendon interface showed expected normal cellular healing at the repair site and the matrix was incorporated into the infraspinatus tendon by multiple fibrous interdigitation and into the bone through a mature fibrocartilaginous transition zone.

In the rat abdominal study, minimal inflammatory response with increasingly organized connective tissue was observed over time from histological evaluation (Fig. 2).  Multinucleate cells were observed within the graft material as time progressed, a response that is typical for a slowly resorbed or nonresorbable implanted material.  There was high degree of tissue infiltration into the patch without necrosis of the surrounding tissue. Additionally, there was minimal scar tissue formation and adhesion within the abdominal space.  The healing response within the matrix and the surrounding tissue was superior to the typical response for other soft tissue meshes

Conclusions:  Biodurable reticulated elastomeric matrix as a TE scaffold shows favorable tissue ingrowth with no adverse effects.  This matrix as a TE scaffold supports collagenous and fibrovascular tissue ingrowth throughout the voids in the scaffold, enabling the healing and repair of damaged tissue.  These scaffolds have been shown to increase the mechanical reinforcement of a chronic RC repair and solicit favorable healing of defects in the abdominal wall.  This healing response is characterized by the interdigitation of organized dense collagenous tissue and bone for RC repair and characterized by organized connective tissue for abdominal wall defect repair.

  

References:

1.Liu, X and Ma, P.X, Annals Biomed. Eng, 32 (3), 477, 2004.

2.Peter, S.J., Miller, M.J., Yasako, A.W., Mikos, A.G., J. Biomed. Mater. Res., 43, 422 , 1998

3.Gerber C., Fuchs B. and Hodler J., J Bone Joint Surg, 82,505, 2000.

4. Harryman, Mack, Wang, J Bone Joint Surg,73, 1991.

5. Klosterhalfen, B., Junge, K. and Klinge, U., Exprt Rev. Med. Devices 2 (1), 2005.

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