Fabrication and evaluation of an optimized xenogenic decellularized costal cartilage graft: preclinical studies of a novel biocompatible prosthesis for rhinoplasty

Abstract

On account of the poor biocompatibility of synthetic prosthesis, millions of rhinoplasty recipients have been forced to choose autologous costal cartilage as grafts, which suffer from limited availability, morbidity at donor site and prolonged operation time. Here, as a promising alternative to autologous costal cartilage, we developed a novel xenogeneic costal cartilage and explored its feasibility as a rhinoplasty graft for the first time. Adopting an improved decellularization protocol, in which the ionic detergent was substituted by trypsin, the resulting decellularized graft was confirmed to preserve more structural components and better mechanics, and eliminate cellular components effectively. The in vitro and in vivo compatibility experiments demonstrated that the decellularized graft showed excellent biocompatibility and biosecurity. Additionally, the functionality assessment of rhinoplasty was performed in a rabbit model, and the condition of grafts after implantation was comprehensively evaluated. The optimized graft exhibited better capacity to reduce the degradation rate and maintain the morphology, in comparison to the decellularized costal cartilage prepared by conventional protocol. These findings indicate that this optimized graft derived from decellularized xenogeneic costal cartilage provides a new prospective for future investigations of rhinoplasty prosthesis and has great potential for clinical application.

Production of a Low-Cost, Off-the-Shelf, Decellularized Cartilage Xenograft for Tissue Regeneration

“…Such substances lyse cellular and intracellular membranes while also denaturing proteins, thus leaving a substantially degraded, albeit decellularized end product bearing little resemblance to its original state with respect to both physical and chemical properties. 14,15,17 To the best of our knowledge, this article is the first to describe the successful decellularization of ovine costal cartilage producing a versatile decellularized graftable material with a relatively preserved tissue architecture. It is also one of the few manuscripts to describe decellularization of costal cartilage from any animal species.…”

“…To the best of our knowledge, this article is the first to describe the successful decellularization of ovine costal cartilage producing a versatile decellularized graftable material with a relatively preserved tissue architecture. It is also one of the few manuscripts to describe decellularization of costal cartilage from any animal species 9,14,18,19 . Given the United States Food and Drug Administration's paradigm requiring orthotopic validation of engineered tissue in animals, the protocol outlined herein offers a predictable, inexpensive and validated model with immediate translational potential to in vitro studies as well as both orthotopic and heterotopic animal studies, thereby greatly expanding access to acellular xenograft for any laboratory whose research might require its use 1 …”

“…Achieving successful decellularization of cartilage, a uniquely dense, avascular, and intricate tissue, has many challenges. [11][12][13][14][15] Although freeze-thaw cycles, agitation, and osmotic shock overwhelmingly preserve ECM proteins, previous work has demonstrated that these methods alone do not lead to sufficient decellularization but need to be supplemented with adjunct chemical and enzymatic decellularization techniques. 10,11,13,14,16 However, several available protocols to chemically decellularize cartilage do so at the expense of its native structure via use of ionic detergents.…”

“…It is also one of the few manuscripts to describe decellularization of costal cartilage from any animal species. 9,14,18,19 Given the United States Food and Drug Administration's paradigm requiring orthotopic validation of engineered tissue in animals, the protocol outlined herein offers a predictable, inexpensive and validated model with immediate translational potential to in vitro studies as well as both orthotopic and heterotopic animal studies, thereby greatly expanding access to acellular xenograft for any laboratory whose research might require its use. 1 There are 3 widely accepted criteria for characterizing decellularized tissue as described by Badylak 10 : (1) H&E and/or DAPI staining to demonstrate absence of cells (in this case chondrocytes within lacunae);…”

Efficacy and safety of equine cartilage for rhinoplasty: a multicenter double-blind non-inferiority randomized confirmatory clinical trial

“…In response to this demand, there have been many studies testing various xenograft materials for nasal reconstruction and rhinoplasty, such as porcine dermal collagen [ 13 ], equine pericardium [ 16 ], porcine small intestine submucosa [ 15 ], and bovine [ 27 , 28 ], porcine [ 29 , 30 ], and caprine [ 31 ] cartilages. Of the several xenograft tissues, decellularized cartilage matrix use has been studied, especially in orthopedic surgery for osteochondral regeneration [ 32 ] and plastic surgery for facial reconstruction [ 31 ].…”