title: Regenerative properties of fetal sheep tendon are not adversely affected by transplantation into an adult environment.
abstract: Tendon injuries account for a significant number of musculoskeletal afflictions each year. While new surgical techniques and rehabilitation protocols have led to improved clinical outcomes, postsurgical scarring remains the most problematic aspect of tendon repair. In contrast to this typical pattern of fibrosis, recent studies have shown that fetal tendon is capable of healing without scar. However, whether this regenerative healing pattern is intrinsic to the fetal tissue itself or the result of its environment is not known. Thus, the objective of this study is to examine the influence of an adult environment on healing in adult and fetal tendons. We hypothesized that injured fetal tendon tissue transplanted into an adult environment would retain a regenerative healing pattern after injury, demonstrating normal histological and mechanical properties. Our results support this hypothesis. Histological analyses revealed considerable alterations in adult tendon transplants after injury while fetal transplants showed no abnormalities. The injured adult tendons also demonstrated elevated levels of TGF-beta1, bFGF, and CD44 at the wound site, whereas the fetal specimens showed little or no such changes in response to injury. The data from our biomechanical studies further corroborate these observations, with significant decreases in the stiffness, modulus, and almost all viscoelastic properties in wounded versus unwounded adult tendons, and fetal specimens showing no differences in mechanical properties between the wounded and unwounded groups. Thus, the results of our investigation demonstrate that the adult environment is not an impediment to scarless repair and that this capability is intrinsic to the fetal tendon itself. Our study also begins to provide insight into the mechanisms controlling this regenerative response.
authors.affiliation: McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania, and Center for Molecular Fetal Therapy, Cincinnati Children's Hospital, OH, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Favata
authors.forename: Pedro K
authors.initials: PK
authors.lastname: Beredjiklian
authors.forename: Miltiadis H
authors.initials: MH
authors.lastname: Zgonis
authors.forename: David P
authors.initials: DP
authors.lastname: Beason
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Crombleholme
authors.forename: Abbas F
authors.initials: AF
authors.lastname: Jawad
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Soslowsky
mesh_terms: D000367:Age Factors; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002921:Cicatrix / Q000378:metabolism / Q000473:pathology; D016332:Fetal Tissue Transplantation; D005333:Fetus / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000378:metabolism; D023421:Models, Animal; D018583:Pliability; D012038:Regeneration / Q000502:physiology*; D012756:Sheep; D013708:Tendon Injuries / Q000196:embryology / Q000601:surgery*; D013710:Tendons / Q000378:metabolism / Q000502:physiology* / Q000637:transplantation*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
chemical_list: D015415:Biomarkers; D018960:Hyaluronan Receptors; D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2