Soft Tissue to Bone Healing in Rotator Cuff Repair - Structural Interfaces and Attachments in Biology - page 260

increased tensile strength and stiffness of the repair [ 71 ]. FGF is active in various
phases of tendon healing and promotes connective tissue formation and remodeling.
It also activates the release of other growth factors such as TGF s and BMPs. Used

in a rat model, FGF improved biomechanical and histological properties 2 weeks
after repair, but the results did not persist at 4 and 6 week time points [ 72 ].
TGF

b

3 is a compelling growth factor for enhancing repair, as it is associated
with scarless soft tissue healing of tendon and skin in early stages of development.
In one rat study, sustained delivery of the growth factor to the rotator cuff healing
site was facilitated using a heparin-binding fibrin matrix [ 73 ]. There were improve-
ments in cellularity, vascularity, and cell proliferation in the reparative tissue.
Structural properties were improved 4 weeks after repair. In another rat study, a
calcium phosphate matrix with TGF

b

3 was used to augment the repair [ 74 ]. The
load-to-failure was improved in these repairs compared to untreated controls and
compared to the calcium phosphate matrix alone. Bone volume was increased at the
attachment site based on computed tomography evaluation. The ratio of collagen I:
III was increased, indicating a more regenerative rather than scar-mediated healing
response. While no growth factor is currently approved for use in rotator cuff repair,
there is great potential for their use in future clinical cuff applications.

b

12.7.2 Matrix Metalloproteinases

MMPs are a family of proteinases that are involved in the maintenance and
remodeling of extracellular matrices on connective tissue. They work in concert
with tissue inhibitors of MMPs (TIMPs) to maintain homeostasis of the remodeling
process and a balance between reparative and degenerative processes. MMPs have
a role in injury response, age related degenerative processes, and repair. Doxycy-
cline is an MMP inhibitor, and its use in a rat model of injury and repair resulted in
some biomechanical improvements as well as improved collagen organization at
early time points [ 75 ]. Alpha 2-macroglobulin is another inhibitor of MMPs. While
some qualitative increase in fibrocartilage formation was identified at the healing
site using this inhibitor, there were no improvements in biomechanical properties of
the repair [ 76 ].

12.7.3 Tissue Engineering

Recently, an explosion of interest in tissue engineering strategies for use in rotator
cuff repair has occurred, with the goal of not only improving biomechanical
strength of the repair, but also utilizing a scaffold for delivery of cells and growth
factors. Some early studies have utilized polyurethane mesh patches with some
success [ 77 ]. Nanofiber scaffolds of PLGA with a novel distribution of mineralized
and unmineralized regions have recently been investigated [ 78 ]. In one study,