Characterization of Macroporous Polycaprolactone/Silk Fibroin/Gelatin/Ascorbic Acid Composite Scaffolds and In Vivo Results in a Rabbit Model for Meniscus Cartilage Repair

Abstract

Objective Meniscus injuries in the inner avascular zone have weak intrinsic self-healing capacity and often progress to osteoarthritis. This study focused on evaluating the effects of polycaprolactone/silk fibroin/gelatin/ascorbic acid (PCL/SF/Gel/AA) composite scaffolds seeded with adipose-derived mesenchymal stem cells (ASCs), in the meniscus repair. Design To this end, composite scaffolds were cross-linked using N-hydroxysuccinimide and 1-ethyl-3-(3-dimethyl-aminopropyl)-1-carbodiimide hydrochloride. Scaffolds were then characterized by scanning electron microscope, mechanical tests, total antioxidant capacity, swelling, and toxicity tests. Results The PCL/SF/Gel/AA scaffolds exhibited suitable mechanical properties. Furthermore, vitamin C rendered them the highest antioxidant capacity. The PCL/SF/Gel/AA scaffolds also showed good biocompatibility and proliferation for chondrocytes. Moreover, the PCL/SF/Gel/AA scaffold seeded with allogeneic ASCs was engrafted in New Zealand rabbits who underwent unilateral punch defect in the medial meniscus of the right knee. After 2 months postimplantation, macroscopic and histologic studies for new meniscus cartilage were performed. Conclusions Our results indicated that the PCL/SF/Gel/AA composite scaffolds seeded with allogeneic ASCs could successfully improve meniscus healing in damaged rabbits.

Total meniscus replacement with a 3D printing of network hydrogel composite scaffold in a rabbit model

“…For instance, in our study, the scaffolds' stability, established by fibres through bone tunnels, failed to completely alleviate the degenerative forces on the cartilage. Previous animal studies [1, 2, 4, 16] have reported improved meniscal stability and enhanced mechanical properties using similar techniques. However, it should be noted that they also resulted in cartilage damage on the tibial plateau.…”

Evaluating osteogenic effects associated with the incorporation of ascorbic acid in mineralized collagen scaffolds

“…Hashemi et al demonstrated a consistent trend of decreasing compression strength with increasing ascorbic acid concentration (0%–10%) in a PLA/PCL/Gelatin composite scaffold 54 . However, incorporation of gelatin and ascorbic acid into a PCL/silk fibroin scaffold increased tensile modulus, 41 and the incorporation of 0.1 wt% ascorbic acid into a hydrated, PLA‐based scaffold increased hydrophilicity and ultimate tensile strength, though these changes were not observed in the dry state 40 . While we have previously demonstrated that hydration state does not alter relative mechanical differences between groups in our mineralized collagen scaffolds, there remain several possible mechanisms through which ascorbic acid incorporation could be bringing about these observed changes.…”

“…In 2D cell culture, ascorbic acid media supplementation in MSC culture has been associated with enhanced wound healing and osteogenesis, resulting in increased mineralization and upregulation of osteogenic gene markers COL1A1 , RUNX2 , BMP‐2/4 , OPN , and SPARC on the order of 1.5‐fold change 37,38 . In the field of biomaterials, ascorbic acid has been investigated for use with a variety of tissues as a media supplement, such as in a polyethylene glycol (PEG)‐based scaffold for aortic valve interstitial cells, 39 and as a material component, as incorporated in a polylactic acid (PLA)‐based scaffold for pelvic floor repair 40 and a polycaprolactone (PCL)‐based scaffold for meniscus repair 41 . Due to its role in collagen synthesis and bone development, ascorbic acid has also become an especially popular component of incorporation in biomaterials for bone regeneration.…”

“…37,38 In the field of biomaterials, ascorbic acid has been investigated for use with a variety of tissues as a media supplement, such as in a polyethylene glycol (PEG)-based scaffold for aortic valve interstitial cells, 39 and as a material component, as incorporated in a polylactic acid (PLA)-based scaffold for pelvic floor repair 40 and a polycaprolactone (PCL)-based scaffold for meniscus repair. 41 Due to its role in collagen synthesis and bone development, ascorbic acid has also become an especially popular component of incorporation in biomaterials for bone regeneration. Hollinger et al described a porous polyurethane scaffold fabricated via lysinedi-isocyanate and glycerol that contained ascorbic acid, finding that the addition of this key vitamin improved production of type 1 collagen as well as cell proliferation and alkaline phosphatase (ALP) activity in murine cells over a span of 2 weeks.…”

Demineralized Cortical Bone Matrix Augmented With Peripheral Blood-Derived Mesenchymal Stem Cells for Rabbit Medial Meniscal Reconstruction

“…Some previous studies have also come up with results on this topic. A recent study indicated that the PCL/SF/Gel/AA composite scaffolds seeded with allogeneic ASCs could successfully improve meniscus healing in damaged rabbits ( Abpeikar et al, 2021 ). However, synthetic materials risk degradation-related toxicity, stress shielding, changes in cellular phenotype, and tissue remodeling ( Lee et al, 2017 ).…”