Soft skeletal tissues, such as tendon and ligament, when injured, have limited regeneration potential. Current surgical repair strategies lack a method to stimulate soft tissue reintegration with surrounding bone, resulting in poor long-term functionality. Thus, there is a strong clinical need for improved soft tissue-to-bone repair materials that provide both immediate mechanical stability and offer a native architecture that supports cellular activity and promotes tissue remodeling and enhanced integration strength over time. This technology offers synthetic, polymer nanofiber mesh-based, cellular and acellular systems for soft tissue-to-bone repair. It has been shown both in vitro and in vivo to improve mechanical performance of the repair in rotator cuff and anterior cruciate ligament (ACL) injuries.
Tendon-bone scaffolds for enhanced integration strength when compared to classical fixation
The multi-phasic nature of the nanofiber scaffolding system makes this technology a viable tendon or ligament alternative. With tunable fiber orientation, the functional properties can be selectively enhanced to resemble the structural organization of native tissue collagens. Seeding with cells lengthens the lifetime of the graft, by guiding cell attachment and matrix development within a physiologically appropriate structure. These nanofibers modulate cellular signaling spatially along the length of the graft which influences integrin expression and matrix deposition. This technology further describes an acellular nanofiber mesh graft collar that can be wrapped around soft tissue to apply compressive mechanical loading, as well as growth factors, to tendon grafts and induce the formation of an anatomic fibrocartilage interface as the soft tissue transitions to bone.
These grafts are similar in function to donor allograft tissue but outperform this alternative in terms of fixation and cell viability. In vitro mechanical tests, as well as in vivo animal injury models (ACL and rotator cuff), have been performed.
Lead Inventor:
Helen Lu, Ph.D.
Applications:
- Shoulder injuries, e.g. rotator cuff tears
- Chronic rotator cuff degeneration
- Knee injuries, e.g. ACL tear
- Other tissue-tissue interface regeneration treatments
- Tissue engineering of skeletal tissues
- Tissue engineering of tissues that transition
Advantages:
- Targets the tendon-bone interface, critical for treatment success and currently not regenerated during repairs
- Offers improved biocompatibility and mechanical strength over existing synthetic tendon grafts
- Treatment is applicable to both serious joint injuries and chronic joint degradation cases
- Design can be applied beyond joint tissue regeneration
- A unified platform for the production of various skeletal tissues from a single cell source
- Properties of the biomaterial are tunable
- Stem cell fate guidance
- Can be used with and without cells
Patent Information:
Patent Pending (US 20130280318)
Patent Pending (WO/2009/038808)
Patent Pending (WO/2008/070186)
Patent Pending (WO/2008/154035)
Patent Pending (WO/2008/100534)
Patent Pending (US 20060067969)
Tech Ventures Reference: IR 1503, 2128, 2169, 2852, 2850, 2414
Related Publications:
Subramony SD, Su A, Yeager K, Lu HH. “Combined effects of chemical priming and mechanical stimulation on mesenchymal stem cell differentiation on nanofiber scaffolds” J. Biomech. 2014 Jun 27;47(9):2189-96.
Subramony SD, Dargis BR, Castillo M, Azeloglu EU, Tracey MS, Su A, Lu HH. “The guidance of stem cell differentiation by substrate alignment and mechanical stimulation” Biomaterials. 2013 Mar;34(8):1942-53.
C Erisken, X Zhang, KL Moffat, WN Levine, HH Lu. “Scaffold Fiber Diameter Regulates Human Tendon Fibroblast Growth and Differentiation” Tissue Engineering Part A. 2013 Feb, 19(3-4):519-28.
Padmaraju K, Chan J, Chen L, Lipson M, Bergman K. “Thermal stabilization of a microring modulator using feedback control” Opt Express. 2012 Dec 17;20(27):27999-8008.
KL Moffat, ASP Kwei, JP Spalazzi, SP Doty, WN Levine, HH Lu. “Novel Nanofiber-Based Scaffold for Rotator Cuff Repair and Augmentation” Tissue Engineering Part A. 2009 Jan, 15(1):115-126.
Moffat KL, Wang IE, Rodeo SA and Lu HH; “Orthopaedic interface tissue engineering for the biological fixation of soft tissue grafts” Clinics in Sports Medicine, 28(1):157-176, 2009.
Moffat KL, Sun WA, Pena PE, Chahine NO, Doty SB, Ateshian GA, Hung CT, Lu HH; “Characterization of the structure-function relationship at the ligament-to-bone interface” Proceedings of the National Academy of Sciences, 105(23): 7947-7952, 2008.
Lu et al., “Compositional effects on the formation of a calcium phosphate layer and the response of osteoblast-like cells on polymer-bioactive glass composites” Biomaterials Volume 26, Issue 32, Pages 6323-6334, November 2005.