Biomedical Engineering Reference
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results. These include integrating the calcium into the tendon graft [ 24 ], injectable
tricalcium phosphate [ 93 ], hydroxyapatite (HA) cement [ 94 ], HA powder in
collagen gel [ 95 ], and magnesium-based bone adhesive [ 96 ].
Another scaffold that has been studied extensively is the periosteum.
Periosteum contains multipotent mesodermal cells, chondroprogenitor, and
osteoprogenitor cells [ 97 - 100 ]. Periosteum-enveloped grafts have been shown
to have improved histologic and biomechanical parameters [ 101 ]. There has
been some clinical experience with periosteum graft augmentation. Robert and
Es-Sayeh used a periosteal flap harvested from the superior and medial
metaphysis of the tibia and wrapped it around the proximal aspect of the four-
strandgraftneartheoutletofthefemoraltunnel[ 102 ]. The augmented group
demonstrated a significant reduction in enlargement of the articular side of the
tunnel. In a prospective case series, Chen et al. reported good clinical results as
measured by instrumented laxity, Lysholm, and International Knee Documenta-
tion Committee scores in 62 patients who were evaluated at 2 years after recon-
struction with hamstring graft augmented with periosteum [ 103 ].Thesamegroup
published a larger series of 312 patients with a similar graft technique and good
clinical objective and subjective outcomes at mean follow-up of 4.6 years [ 104 ].
It is important to note that none of these series had a control group of standard
hamstring ACL reconstruction for comparison.
13.5.3 Cell and Gene Therapy
The concept of using periosteum as a natural source of delivering progenitor cells to
the tendon-bone interface has been expanded to include the delivery of various cell
types through many different mechanisms. Chen et al. used a hydrogel with
photoencapsulated periosteal progenitor cells and BMP-2 to improve histologic
healing, pullout strength, and stiffness in a rabbit ACL reconstruction model [ 105 ].
Others have used autologous mesenchymal stem cells [ 23 , 106 , 107 ], synovial
mesenchymal stem cells [ 108 ], and bone marrow aspirates [ 109 ] to demonstrate
improved graft-tunnel healing.
One of the limitations of direct delivery of growth factors and biomaterials is the
inability to provide a sustained and prolonged exposure. This challenge may be able
to be met with advancements in gene therapy. Martinek et al. used a tendon graft
infected with adenovirus-BMP-2 gene to significantly improve histologic healing
parameters as well as stiffness and ultimate load-to-failure [ 110 ]. Wang et al.
demonstrated similar results using a plasmid cytomegalovirus BMP-2 delivery
system in a rabbit model [ 111 ]. While promising, gene therapy techniques have
additional safety and regulatory issues that add complexity to their transition into
clinical practice.
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