Enthesis Healing Is Dependent on Scaffold Interphase Morphology—Results from a Rodent Patellar Model

Abstract

The use of multiphasic scaffolds to treat injured tendon-to-bone entheses has shown promising results in vitro. Here, we used two versions of a biphasic silk fibroin scaffold to treat an enthesis defect created in a rat patellar model in vivo. One version presented a mixed transition between the bony and the tendon end of the construct (S-MT) while this transition was abrupt in the second version (S-AT). At 12 weeks after surgery, the S-MT scaffold promoted better healing of the injured enthesis, with minimal undesired ossification of the insertion area. The expression of tenogenic and chondrogenic markers was sustained for longer in the S-MT-treated group and the tangent modulus of the S-MT-treated samples was similar to the native tissue at 12 weeks while that of the S-AT-treated enthesis was lower. Our study highlights the important role of the transition zone of multiphasic scaffolds in the treatment of complex interphase tissues such as the tendon-to-bone enthesis.

Co-Culture of Mesenchymal Stem Cells and Ligamentocytes on Triphasic Embroidered Poly(L-lactide-co-ε-caprolactone) and Polylactic Acid Scaffolds for Anterior Cruciate Ligament Enthesis Tissue Engineering

“…Although the autologous graft materials used today are successful, the re-rupture rate is still too high (overall 4.8% depending on the surgery technique) [ 50 ], and therefore, the orthopedic research community is striving to find a tissue-engineered construct as an option to overcome the problem of limited autograft availability. In the past few years, new approaches and techniques, such as modification of decellularized native enthesis tissue, silk [ 51 , 52 , 53 ] or polymer based scaffolds [ 25 , 54 ], have been investigated for their reconstruction capabilities for the complete enthesis zone and not only the ligament zone of the ACL, the patellar tendon or the rotator cuff [ 25 , 51 , 52 , 53 ]. The importance of creating multiphasic scaffolds for musculoskeletal interface tissue engineering to achieve functional restoration of injured zonal tissues has increased in past years not only in orthopedics but also in dentistry [ 55 , 56 , 57 , 58 ].…”

Biomimetic gradient scaffolds for the tissue engineering and regeneration of rotator cuff enthesis

“…In recent decades, biomimetic scaffolds for TBI regeneration have been made from a variety of materials, including natural polymers, synthetic polymers, bioceramics, and composite materials [60][61][62][63][64][65][66]. Collagen is the most commonly used natural polymer due to its prominence in the ECM with minimal host immune response [67,68].…”

Interfacial Tissue Regeneration with Bone

“…Biomaterials have proven to be a more popular method for interfacial tissue repair as they offer a more controllable system without the complexity of cell implantation (i.e., cells are challenging to scale-up production reproducibly for transplant) [ 95 , 96 ]. There are several approaches to biomaterial design for interfacial tissue regeneration including synthetic vs. natural constructs, injectable vs. non-injectable materials, 3D-printed vs. electrospun, degradable vs. non-degradable, and multi-phasic vs. uni-phasic [ 97 – 104 , 105 ••]. Currently, substantial progress has been made in osteochondral interfacial regeneration with bone using biomaterials, particularly in craniofacial bone defects [ 91 , 97 , 106 – 109 ].…”