Achilles Tendon Repair by Decellularized and Engineered Xenografts in a Rabbit Model

Abstract

Tendon tissue ruptures often require the replacement of damaged tissues. The use of auto- or allografts is notoriously limited due to the scarce supply and the high risks of immune adverse reactions. To overcome these limitations, tissue engineering (TE) has been considered a promising approach. Among several biomaterials, decellularized xenografts are available in large quantity and could represent a possible solution for tendon reconstruction. The present study is aimed at evaluating TE xenografts in Achilles tendon defects. Specifically, the ability to enhance the biomechanical functionality, while improving the graft interaction with the host, was tested. The combination of decellularized equine-derived tendon xenografts with or without the matrix repopulation with autologous bone marrow mesenchymal stem cells (BMSCs) under stretch-perfusion dynamic conditions might improve the side-to-side tendon reconstruction. Thirty-six New Zealand rabbits were used to create 2 cm long segmental defects of the Achilles tendon. Then, animals were implanted with autograft (AG) as the gold standard control, decellularized graft (DG), or in vitro tissue-engineered graft (TEG) and evaluated postoperatively at 12 weeks. After sacrifice, histological, immunohistochemical, biochemical, and biomechanical analyses were performed along with the matrix metalloproteinases. The results demonstrated the beneficial role of undifferentiated BMSCs loaded within decellularized xenografts undergoing a stretch-perfusion culture as an immunomodulatory weapon reducing the inflammatory process. Interestingly, AG and TEG groups exhibited similar results, behaved similarly, and showed a significant superior tissue healing compared to DG in terms of newly formed collagen fibres and biomechanical parameters. Whereas, DG demonstrated a massive inflammatory and giant cell response associated with graft destruction and necrosis, absence of type I and III collagen, and a higher amount of proteoglycans and MMP-2, thus unfavourably affecting the biomechanical response. In conclusion, this in vivo study suggests a potential use of the proposed tissue-engineered constructs for tendon reconstruction.

Cell-Free Book-Shaped Decellularized Tendon Matrix Graft Capable of Controlled Release of BMP-12 to Improve Tendon Healing in a Rat Model

“…When the NAT-BMP-12/IDTM, NAT-BMP-12/BDTM, CBD-BMP-12/IDTM, and CBD-BMP-12/BDTM were used in patching rat AT defects, they were more like a xenograft. Although the DTM is thought to have low immunogenicity, the NAT-BMP-12/IDTM, NAT-BMP-12/BDTM, CBD-BMP-12/IDTM, and CBD-BMP-12/BDTM as a xenograft remain more immunogenic than the autograft, which may stimulate more local inflammatory response at the repair site than the autograft, 5 which was a negative factor for tendinous tissue formation. Given that the BMP-12 is released from NAT-BMP-12/IDTM and NAT-BMP-12/BDTM in a burst pattern in vivo, limited endogenous stem cells migrated into the defect site and differentiated into tenocytes; thus, the defect did not heal as well as in the autograft group.…”

Adipose Micro-Grafts Enhance Tendinopathy Healing in Ovine Model: An in Vivo Experimental Perspective Study

“…25 Surgical interventions may be an option in restoring or substituting the injured tendon using direct suture or autograft, 26 allografts, xenografts, or prosthetics. 27,28 Nevertheless, inflammation and suture retention weakness prevent an optimal clinical outcome and the increase in treatment cost is to be acknowledged. 29 Indeed, the increased incidence rate and ineffective treatments of MSDs have resulted in a rise of up to $874 billion from 2000 to 2015.…”

“…For decades, surgeons have argued, despite the lack of general consensus in the literature, that rest, consolidated physiotherapy exercises (as first‐line management given the satisfactory results in 25‐45% of cases), and surgery (as a final option) are gold standard managements for tendinopathy 25 . Surgical interventions may be an option in restoring or substituting the injured tendon using direct suture or autograft, 26 allografts, xenografts, or prosthetics 27,28 …”

“… 25 Surgical interventions may be an option in restoring or substituting the injured tendon using direct suture or autograft, 26 allografts, xenografts, or prosthetics. 27 , 28 …”

A Collagen Basketweave from the Giant Squid Mantle as a Robust Scaffold for Tissue Engineering

“…The distinctions between them stem from the connections they create; ligaments connect a bone with another bone, and tendons connect a muscle with a bone. A number of studies are dedicated to the restoration of tendon ruptures using different materials [14,15].…”