Adhesions in a murine flexor tendon graft model: Autograft versus allograft reconstruction

Abstract

Reconstruction of flexor tendons often results in adhesions that compromise joint flexion. Little is known about the factors involved in the formation of flexor tendon graft adhesions. In this study, we developed and characterized a novel mouse model of flexor digitorum longus (FDL) tendon reconstruction with live autografts or reconstituted freeze-dried allografts. Grafted tendons were evaluated at multiple time points up to 84 days post-reconstruction. To assess the flexion range of the metatarsophalangeal joint, we developed a quantitative outcome measure proportional to the resistance to tendon gliding due to adhesions, which we termed the Gliding Coefficient. At 14 days post-grafting, the Gliding Coefficient was 29-and 26-fold greater than normal FDL tendon for both autografts and allografts, respectively (p < 0.001), and subsequently doubled for 28-day autografts. Interestingly, there were no significant differences in maximum tensile force or stiffness between live autograft and freeze-dried allograft repairs over time. Histologically, autograft healing was characterized by extensive remodeling and exuberant scarring around both the ends and the body of the graft, whereas allograft scarring was abundant only near the graft-host junctions. Gene expression of GDF-5 and VEGF were significantly increased in 28-day autografts compared to allografts and to normal tendons. These results suggest that the biomechanical advantages for tendon reconstruction using live autografts over devitalized allografts are minimal. This mouse model can be useful in elucidating the molecular mechanisms in tendon repair and can aid in preliminary screening of molecular treatments of flexor tendon adhesions. ß

Tendon injury and repair – A perspective on the basic mechanisms of tendon disease and future clinical therapy

“…Augmentation should aim to facilitate optimal tissue templating and initial tissue remodeling -setting the longer-term repair process onto a good track. -Guiding appropriate tissue compartmentalization is well appreciated in the context of preventing formation of adhesions between the tendon sheath and surrounding tissues [204][205][206]210]. However, the subtler need for appropriate ''internal compartmentalization" is less well recognized (Fig.…”

“…Although autograft material immediately provides a well-structured tissue with potentially appropriate material properties, cell-matrix remodeling typically resets the structure of the graft, and can resemble healing stages after tendon injury or even tendinopathy. The result is diminished mechanical properties compared to the initial graft, decreased structural quality of the tissue [240] and occasional adhesion formation [210].…”

The past, present and future in scaffold-based tendon treatments

“…vascular endothelial cells, fibroblasts and stem cells) not usually seen in healthy tendons [107]. These cells could dominate endogenous TCs, especially with respect to cellular secretome, resulting in compromised functionality [118] and adhesion formation that are associated with pain and locomotion issues [119]. As a result of these changes, mechanical, structural, biochemical and biological properties of the healed tendon never match those of the tissue prior to injury [64].…”

Chondrogenic Differentiation of Adipose-Derived Adult Stem Cells by a Porous Scaffold Derived from Native Articular Cartilage Extracellular Matrix

“…Recently, decellularized scaffolds derived from a variety of intact tissues have been applied in engineering different tissues or organs, including tendons, ligaments, blood vessels, skin, nerves, skeletal muscle, small intestinal submucosa, urinary bladder, heart, and liver. [75][76][77][78][79][80][81] Decellularized and lyophilized osteochondral grafts have also been used successfully to treat full-thickness cartilage lesions in a rabbit model. 82 In the present study, we adopted a relatively simple yet effective method to reconstitute the cartilage tissue into a threedimensional porous structure with a porosity of *95% and an interconnected network of pores with an average pore size of 221 mm (Fig.…”