Researchers at Birjand University of Medical Sciences and collaborating Iranian institutions set out to solve a problem that is both biological and geopolitical. The most promising biological scaffolds for meniscus replacement have often come from pigs, whose tissue closely resembles our own. But across Iran and much of the Middle East, porcine material is culturally and religiously inaccessible, and human donor menisci are in short supply. The team therefore turned to two regionally abundant species, the sheep and the dromedary camel, and asked a deceptively simple question: if you strip the cells out of their menisci, leaving behind only the collagenous framework, how closely does the resulting scaffold match what human tissue can offer?

The answer required an unusually thorough decellularization protocol. Whole menisci from camels and sheep were collected from a local abattoir, while human specimens came from patients undergoing total knee arthroplasty. Each tissue then endured a punishing chemical gauntlet: repeated freeze-thaw cycles to rupture cell membranes, trypsin digestion, two rounds of the detergent Triton X-100, a 72-hour bath in sodium lauryl ether sulfate with EDTA, and a final treatment with peracetic acid to open pores and purge lingering cellular debris. The goal is a paradox familiar to tissue engineers: kill and remove every cell while leaving the intricate extracellular matrix, the collagen fibers and proteoglycans that give the meniscus its strength, essentially untouched.

By the standard benchmarks, the protocol succeeded. Residual DNA fell to 29.67 nanograms per milligram of dry weight in camel scaffolds, 22.33 in human, and 19.67 in sheep, all comfortably below the internationally accepted threshold of 50 nanograms per milligram that signals successful decellularization. Histological staining confirmed that cell nuclei had vanished from both the peripheral and central zones. Yet the process was not without cost. Glycosaminoglycans, the water-loving sugar chains that help the meniscus resist compression, dropped significantly in every species, a well-known vulnerability of these highly soluble molecules to detergent-based processing.

What survived, remarkably, was the architecture. Scanning electron microscopy showed that the highly aligned circumferential collagen network, the load-bearing skeleton of the meniscus, remained intact in all three species, with directionality goodness-of-fit values above 0.8. Decellularized fibers were actually thicker than native ones, swelling from roughly 1.7 to 2.4 micrometers in camel tissue, likely because removing proteoglycans released the compacted fibrils from their molecular tethers. Porosity also rose substantially, from about 20 percent to nearly 32 percent in camel scaffolds, with mean pore sizes expanding to over 129 square micrometers, changes that should ease cell migration and nutrient diffusion once the scaffold is implanted.

Mechanical testing delivered the study’s most encouraging numbers. Although decellularization softened all three tissues, the camel scaffold’s compressive modulus of 1.12 megapascals remained statistically indistinguishable from that of decellularized human meniscus at 0.86 megapascals, despite the camel’s roughly 20 percent numerical advantage. Ultimate tensile strength showed no significant decline in any species after processing, evidence that the circumferential collagen architecture retained its ability to carry tension along the meniscus’s primary load-bearing axis. The researchers attribute this resilience to two factors: the preserved network of circumferential and radial fibers that confines the tissue laterally under compression, and the camel meniscus’s inherently dense native collagen, which the protocol preserved across all groups.

The decisive test came in living tissue. The team implanted small squares of each scaffold under the skin of rats and tracked the immune response over four weeks. In the first week, all three xenogeneic materials provoked comparable acute inflammation, an expected reaction to foreign tissue. By week four, however, the paths diverged sharply. Camel scaffolds showed attenuated inflammation, vigorous migration of fibroblasts deep into the scaffold interior, and signs of active remodeling. Human scaffolds, paradoxically, retained persistent inflammatory infiltrates at their periphery with little fibroblast penetration, while sheep scaffolds showed reduced inflammation but less cellular integration than camel tissue. Quantitative histomorphometry confirmed that camel scaffolds also retained significantly more of their original area, indicating slower degradation and superior structural stability during the critical early remodeling window.

Laboratory assays reinforced the in vivo picture. NIH 3T3 fibroblasts adhered and spread on all three scaffolds, and MTT viability tests showed no cytotoxicity and no meaningful differences among the materials. Co-culture with Jurkat T-lymphocytes revealed that all xenogeneic scaffolds stimulated more T-cell proliferation than flat 2D culture, an honest reminder that animal-derived matrices are not immunologically invisible; camel scaffolds trended toward the lowest proliferation, but the differences did not reach statistical significance. Raman spectroscopy added a molecular fingerprint, detecting preserved collagen-associated peaks including amide I at 1658 and amide III at 1237 inverse centimeters, which could serve as batch-verification markers in future manufacturing. Enzymatic degradation assays told the same durability story: after 14 days in trypsin, camel scaffolds retained 84.31 percent of their mass versus 64.88 percent for human and just 45.23 percent for sheep.

The authors are careful about what these results do and do not mean. In the rat model, all three scaffolds were xenografts; in a human patient, human tissue would behave as an allograft with matched immune recognition, so camel material should be seen as a pragmatic regional alternative rather than an immunological upgrade over human transplants. The subcutaneous implantation site also cannot reproduce the biomechanical complexity of the knee, and the study lacked cyclic fatigue testing under physiological loading. Still, the work establishes the first quantitative anatomical dataset for dromedary camel menisci, showing outer circumferences of 105 to 115 millimeters that even exceed human dimensions, and demonstrates for the first time that camel, human, and sheep scaffolds can be systematically benchmarked against one another. The next milestone will be orthotopic implantation in large-animal knees under dynamic load, the true proving ground for any scaffold that hopes to keep people moving after meniscus loss.

Subject of Research: Decellularized xenogeneic meniscus scaffolds from camel and sheep as alternatives to human meniscus grafts

Article Title: Efficacy of decellularized meniscus xenogeneic substitutes from sheep and camels compared to human menisci

Article References: Khakzad, M. R., Vafaei‐Nezhad, S., Talaei‐Khozani, T., Hassanzadeh‐Taheri, M. M., Rezaeipour, M., Hashemi, H., Shadi, M., & Afshar, M. (2026). Efficacy of decellularized meniscus xenogeneic substitutes from sheep and camels compared to human menisci. Bioengineering & Translational Medicine, Article e70161. https://doi.org/10.1002/btm2.70161

Image Credits: AI Generated

DOI: 10.1002/btm2.70161

Keywords: meniscus, decellularization, tissue engineering, extracellular matrix, xenograft, camel, sheep, biocompatibility, collagen scaffold, knee injury, regenerative medicine, biomechanics