Effect of crosslinking on the performance of a collagen‐derived biomaterial as an implant for soft tissue repair: A rodent model

Abstract

One of the main problems in healthcare is the loss of tissues resulting from diseases, post-surgery complications or trauma. As a result there is a need for biomaterials designed to promote tissue regeneration and improve wound healing. This study assessed the effect of crosslinking of a porcine dermal collagen matrix with regard to strength of implant/host tissue integration, implant biocompatibility and general healing in a rodent model. Permacol™, a crosslinked acellular collagenous biomaterial was compared with its noncrosslinked equivalent at 3, 6, and 12 months postsubcutaneous implantation. Both matrices were well tolerated and showed no evidence of inflammation or adverse responses either in the host tissue or implants. Progressive integration of the implants with the surrounding tissue was observed. Cellular response was similar for both collagenous matrices although, at 3 and 6 months, noncrosslinked implants showed a significantly higher level of cellular penetration than crosslinked implants. However, at 12 months crosslinked implants showed significantly higher levels of cellular density, neo-vascularisation and integration with host tissue. Additionally, at long term, noncrosslinked implants lost volume suggesting some absorption. The crosslinking process does not seem to be detrimental to cellular response and biocompatibility.

Extracellular matrix-based biomaterial scaffolds and the host response

“…The extensive history and ongoing work with this ECM-based biomaterial should serve as the standard for benchmarking future decellularized biomaterial development, informing the biomaterials community as to how to accurately assess preclinical and clinical outcomes and evaluate successes and failures in translation. Importantly, different tissue processing techniques from the same source (i.e., porcine SIS) show markedly different results [198], further complicating the selection and de-risking of new efficacious ECM-based materials, and highlighting the need for detailed material characterization post-decellularization/processing. As more tissues are decellularized and developed as possible clinical products, SIS history should be carefully examined to not repeat the same mistakes, and to emulate relative SIS success with other future ECM-derived implant materials.…”

Mesenchymal Stem Cells Seeded on Cross‐Linked and Noncross‐Linked Acellular Porcine Dermal Scaffolds for Long‐Term Full‐Thickness Hernia Repair in a Small Animal Model

“…Some studies, for example, de Castro et al,13 Macleod et al,17 Smart et al,21 Gaertner et al,22 and O’Brien et al,23 suggest that CL ECM last longer in vivo and have excellent biocompatibility. However, authors such as Butler et al,10 Ayubi et al,18 and Wotton24 suggest that CL ECM are less biocompatible and not as applicable in clinical practice and, furthermore, may actually be at risk of rejection 25.…”

“…The disadvantage of cross-linking is that it decreases biocompatibility and the strength of incorporation (SOI) into the host's tissues. There is an ongoing discussion about how much these properties are affected by cross-linking 10 , 13 - 16…”

Two cross-linked porcine dermal implants in a single patient undergoing hernia repair

“…Reports of encapsulation tend to come from short term studies 15–17. As study length increases both the presence of encapsulation and the overall impression of implant biocompatibility has been shown to improve with diminution of the capsule and significant improvements in cell infiltration, neovascularisation and extracellular matrix (ECM) deposition over time were observed 11 16…”