Mixed Type I and Type II Collagen Scaffold for Cartilage Repair: Ultrastructural Study of Synovial Membrane Response and Healing Potential versus Microfractures (A Pilot Study)

Abstract

The first two authors contributed equally to the manuscriptThe association between microfracture ofthe subchondral plate and a coverage scaffold has emerged as a promising strategy to treat cartilage lesions in a one-step procedure. Between different types of scaffolds (e.g, collagen, hyaluronic acid, polyglycolic acid) currently studied, type I collagen scaffold is the most used for this purpose, and is currently adopted for humans. The aim of this study was to test a novel scaffold made of mixed type I and II collagen (I-IICS) in order to define the immunological reaction of the synovial tissue and the repair capabilities induced by the collagen membrane when associated with microfracture. Eight New Zealand White rabbits, aged 180 days, were operated on bilaterally on the medial femoral condyle. A circular cartilage lesion was performed up to the calcified layer of the medial femoral condyle, and the centre of the lesion was microfractured. Randomly, one of the two lesions was covered with the I-IICS ( treated), and the other was left uncovered (control). The synovial membrane reaction and the quality of the cartilage tissue repair were investigated at 2, 90,180 and 270 days macroscopically, histomorphologically and ultrastructurally. Expression oftumor necrosis factor-alpha (TNF-a) in synovial tissue by immunocytochemistry analyses was also investigated. In the control group, at 2 days gold particles were localized mainly on synoviocyte type A, less on synoviocytes type B and on collagen bundles; in the treated group the reaction is more intense in cells in the matrix, but at 180 days controls and treated joints were very similar. The synovial membranes of the joints receiving the I-IICS did not reveal significant changes compared to the age-matched controls. Signs of inflammation were present at the 90-day time-point, and became less evident at afterwards. The degradation of the scaffolds was already evident at the 90-day time-point. The quality of the cartilage repair of the rabbits treated with the I-IICS was slightly better in 5 cases out of 6 in comparison to the controls. However, a statistically significant difference was not detected (p=0.06). Scaffolds made of mixed type I and II collagen exhibited good biocompatibility properties in vivo and favored cartilage restoration when associated with microfracture, as shown in this pilot study.

Delivering rhFGF‐18 via a bilayer collagen membrane to enhance microfracture treatment of chondral defects in a large animal model

“…The concept of an “augmented microfracture” procedure as a one step cartilage repair is an active area of current research. Recently, enhancement of microfracture techniques by application of stem cells, collagen membranes, ECM biomembranes, and chitosan‐based BST‐CarGel have all shown superior healing compared to microfracture alone. That the presence of a scaffold or membrane alone leads to increased healing has led to the suggestion that these additions are stabilizing or protecting the blood clots formed by the microfracture procedure, supporting the healing of the damaged tissue .…”

Advancing biomaterials of human origin for tissue engineering

“…Although a type I collagen scaffold is most often used for this purpose, biomatrix-scaffolds made of mixed type I and II collagen, which defied the immunological reaction of the synovial tissue, exhibited good biocompatibility in vivo and favored cartilage restoration by the collagen membrane when associated with a microfracture [340]. The limited use of collagen II in scaffolding materials may be potentially due to its limited availability and high cost, the lack of substantial data to support its application, limited consciousness of its utility or a combination of these factors [39].…”

Improved cartilage regeneration by implantation of acellular biomaterials after bone marrow stimulation: a systematic review and meta-analysis of animal studies

“…Acellular biomaterials offer various advantageous properties such as lack of donor-site morbidity, absence of cell culture costs, off the shelf availability, fewer regulatory issues, and application of one-stage surgical procedures ( Brouwer et al, 2011 ; Efe et al, 2012 ). Many researchers have explored the approach of implanting acellular biomaterials and investigated the use of various biomaterials in vivo , such as natural (e.g., collagen ( Breinan et al, 2000 ; Buma et al, 2003 ; Enea et al, 2013 ; Wakitani et al, 1994 ), chitosan ( Abarrategi et al, 2010 ; Bell et al, 2013 ; Guzman-Morales et al, 2014 ; Hoemann et al, 2007 ), alginate ( Igarashi et al, 2012 ; Mierisch et al, 2002 ; Sukegawa et al, 2012 ) and hyaluronic acid ( Aulin et al, 2013 ; Kayakabe et al, 2006 ; Marmotti et al, 2012 ; Solchaga et al, 2000 )) and synthetic polymers (e.g., polycaprolactone ( Christensen et al, 2012 ; Martinez-Diaz et al, 2010 ; Mrosek et al, 2010 ), polyvinyl alcohol ( Coburn et al, 2012 ; Holmes, Volz & Chvapil, 1975 ; Krych et al, 2013 ) and poly(lactic-co-glycolic acid) ( Athanasiou, Korvick & Schenck Jr, 1997 ; Chang et al, 2012 ; Cui, Wu & Hu, 2009 ; Fonseca et al, 2014 )). To combine the advantageous properties of these materials, multilayered biomaterials (e.g., β -tricalcium phosphate-hydroxyapatite/hyaluronate-atelocollagen ( Ahn et al, 2009 ), ceramic bovine bone-gelatin/gelatin-chondroitin sulfate-sodium hyaluronate ( Deng et al, 2012 )), blends (e.g., poly(glycolic acid)-hyaluronic acid ( Erggelet et al, 2009 ) and type I collagen-hyaluronic acid-fibrinogen hydrogel ( Lee et al, 2012 )) have been constructed.…”