In Vivo Characterization of Hyalonect, a Novel Biodegradable Surgical Mesh Nicholas P. Rhodes, Ph.D.,* ,1 John A. Hunt, D.Sc.,* Cristina Longinotti, M.Sc.,† and Alessandra Pavesio, Ph.D.† *UK Centre for Tissue Engineering, University of Liverpool, Division of Clinical Engineering, Liverpool, UK; and †Fidia Advanced Biopolymers, Abano Terme (Padova), Italy Submitted for publication June 11, 2010 Background. Musculoskeletal reconstructive sur- gery often requires removal of significant quantities of bone tissue, such as the periosteum, causing critical problems following surgery like friction between different tissues and adhesion of soft tissues to the un- derlying bone. We studied the long-term host response and closure of large bone defects for periosteal recon- struction using Hyalonect, a novel membrane compris- ing knitted fibers of esterified hyaluronan, (HYAFF11). Materials and Methods. For biological characteriza- tion, 162 rats were used in a defect model in which a section of the dorsal muscular fascia was removed, and the membrane behavior observed over 540 d using conventional histology, with sham operated rats as controls. In addition, Hyalonect was used to cover de- fects made in the humeri of 7 dogs, filled with a variety of conventional bone filling compounds, and the regen- eration process observed after 6 wks using histology. Results. Low levels of inflammation were observed in the dorsal muscle fascia defect model, with cellular colonization of the mesh by 30 d, vascularization by 120 days, matrix fiber organization by 270 d, and the appearance of connective tissue identical to the sur- rounding tissue between 365 and 540 d, without the formation of fibrotic tissue. In addition, Hyalonect was shown to allow the regeneration of bone within the humeral defects whilst preventing fibrotic tissue in-growth, and allowing regeneration of tissue which, by 6 wk, had begun to resemble natural periosteal tissue. Conclusion. Hyalonect is suitable for improving the outcome of the final phases of orthopedic and trauma reconstructive surgical procedures, especially in the reconstruction of periosteal tissue. Ó 2011 Published by Elsevier Inc. Key Words: hyaluronan; HYAFF; esterification; periostium; membrane; reconstruction; mesh; regen- eration. INTRODUCTION Orthopedic and trauma reconstructive surgery in- volving removal of significant portions of bone tissue may pose critical problems during the final phases of surgery. A typical situation is the loss of specialized structures such as the periosteum, which covers bone, or general membranes, which have high strength and lubricity acting to prevent friction between distinct tis- sue groups. The lack of periosteal tissue may lead to dis- persion of engrafted bone substitutes and/or favor adhesion of adjacent soft tissues to the underlying bone. As a consequence, graft stability is compromised and pain can develop at the site where such adhesions may have formed. Additionally, there are frequent occa- sions when there is the need to maintain the relative positions of engrafted bone tissue (autograft, allograft, and bone graft substitutes) or bone graft fragments from comminuted fractures within a defined spatial arrangement. Furthermore, moderate trauma to bone can destroy the structural and functional integrity of the periosteum, which can profoundly influence subsequent regeneration of the bone tissue. The periosteum is a membrane com- posed of fibrous tissues, elastic tissues, and blood vessels, containing osteoblasts and mesenchymal progenitor cells organized in two layers and tightly bound to the bone tissue. It helps control the macro-architecture of the bones and directs metabolic ion exchange and the physiologic distribution of electro-chemical potential 1 To whom correspondence and reprint requests should be ad- dressed at UK Centre for Tissue Engineering, University of Liverpool, Division of Clinical Engineering, Duncan Building, Daulby Street, Liverpool L69 3GA, UK. E-mail: npr@liv.ac.uk. 0022-4804/$36.00 Ó 2011 Published by Elsevier Inc. e31 Journal of Surgical Research 168, e31–e38 (2011) doi:10.1016/j.jss.2010.09.015