Equine model for soft‐tissue regeneration

Abstract

Soft tissue regeneration methods currently yield suboptimal clinical outcomes due to loss of tissue volume and a lack of functional tissue regeneration. Grafted tissues and natural biomaterials often degrade or resorb too quickly, while most synthetic materials do not degrade. In previous research we demonstrated that soft tissue regeneration can be supported using silk porous biomaterials for at least 18 months in vivo in a rodent model. In the present study, we scaled the system to a survival study using a large animal model and demonstrated the feasibility of these biomaterials for soft tissue regeneration in adult horses. Both slow and rapidly degrading silk matrices were evaluated in subcutaneous pocket and intramuscular defect depots. We showed that we can effectively employ an equine model over six months to simultaneously evaluate many different implants, reducing the number of animals needed. Furthermore, we were able to tailor matrix degradation by varying the initial format of the implanted silk. Finally, we demonstrate ultrasound imaging of implants to be an effective means for tracking tissue regeneration and implant degradation.

Silk fibroin photo-lyogels containing microchannels as a biomaterial platform for in situ tissue engineering

“…15,16 A few reports of silk based lyogels have been published and it has been demonstrated that the crosslinked nature of the starting protein network results in unique physicochemical properties compared to lyophilized sponges made by lyophilizing uncrosslinked silk solution. 14,[16][17][18][19] While lyophilized silk sponges have been widely explored and evaluated for applications such as soft tissue, [20][21][22] intervertebral disc, 23 and cardiovascular tissue [24][25][26] augmentation and regeneration, platelet production, 27 and drug delivery, 28,29 silk lyogels are less well characterized. In particular, the properties of silk lyogels made from di-tyrosine crosslinked silk networks have not been explored to date.…”

Microchannels Are an Architectural Cue That Promotes Integration and Vascularization of Silk Biomaterials in Vivo

“…The large number of parameters that can be tuned during silk fibroin processing and scaffold fabrication allows the morphological, mechanical, and degradation properties to be precisely tuned toward a specific application . Lyophilized silk sponges in particular have been explored for a range of regenerative medicine applications ,− and have been demonstrated to be well tolerated and remodeled in vivo . Microchannels engineered into silk scaffolds have been shown to improve tissue ingrowth and stem cell survival at early time points post-implantation, but the effect of microchannels on silk scaffold vascularization has not been studied in detail.…”

Local delivery of dinutuximab from lyophilized silk fibroin foams for treatment of an orthotopic neuroblastoma model

“…The samples were frozen at −20°C overnight, transferred to a −80°C freezer for at least of 30 minutes, and lyophilized. To induce the β‐sheet confirmation of the silk fibroin, thereby altering the material crystallinity and rendering the material insoluble, the lyophilized samples were water‐vapor annealed in the molds for 4 hours and dried at 37°C for 1 hour (Figure ) …”

“…Clinically, silk fibroin has not only been used as suture material, but has also been used in implantable scaffolds . As a drug delivery platform, silk fibroin has been shown to cause minimal immune response in vivo, while allowing for local and sustained release of various chemotherapy agents . Furthermore, lyophilized silk hydrogel systems have shown great promise for local sustained release of monoclonal antibodies …”