SPARCling Matrix

The essential role of the matricellular protein SPARC in tendon disease and healing

Tendons connect muscles to bones and are composed primarily of resilient collagen fibers. They enable movement of our body and withstand considerable mechanical demands. At the same time, they are only sparsely supplied with blood and contain relatively few cells, which is one of the underlying causes of slow and often incomplete healing after injury. Many people develop chronic tendon disorders, known as tendinopathies, at some point in their lives. Previous research from our group has shown that the protein SPARC plays a crucial role in maintaining tendon structure and load-bearing capacity. Its levels decline significantly with age, a change that leads to impaired tendon health. Therefore, the “SPARCling Matrix” project aimed to understand the consequences of SPARC loss in tendon tissue and to explore whether the local delivery of SPARC could improve the healing of injured tendons. In parallel, students together with experts from FH Salzburg, developed a digital tool that objectively and automatically evaluates tissue alterations in histological sections.

In the project, comprehensive analyses of tendons from mice genetically engineered to express little or no SPARC in their tendon tissue were conducted. The findings reveal pronounced alterations in essential metabolic pathways. Lipid metabolism, which provides a major energy source for tendon cells, is particularly affected, and mitochondrial function - the cellular “power plant” -is also compromised. These disruptions suggest that tendons lacking SPARC have reduced resilience and a diminished ability to cope with stress or injury. Overall, the observations point to weakened regenerative potential and greater susceptibility to structural damage.

To investigate whether SPARC could enhance repair, a standardized injury model in the rat knee was employed. Interestingly, a single local administration of SPARC resulted in measurable benefits. Biological processes that promote tissue repair were strengthened, while reactions that typically lead to the formation of stiff, fibrotic scar tissue were reduced. Improvements in tissue organization and mechanical properties were most evident during the initial phase of healing. These results indicate that SPARC may represent a promising biological approach to support tendon repair.

One central objective of the project was to develop an objective, reproducible, and largely automated method for evaluating tendon tissue sections. Together with teachers, experts and citizen scientists, students developed digital analysis tools. These tools can e.g. automatically quantify cell numbers and detect characteristic pathological changes, such as increased deposition of proteoglycans, often occurring in degenerated tendons. Validation studies showed strong agreement between th digital analyses and traditional manual assessments, underscoring the potential of these tools for future use in research.

The insights gained by the project offer a deeper understanding of how tendon disorders arise and progress. They underscore the pivotal role of SPARC in maintaining tendon function and health and demonstrate that targeted SPARC administration can support the healing process. At the same time, the project highlights how digital technologies can help make tissue evaluation more precise, objective, and scalable. These results are now being further explored as part of an ongoing doctoral thesis at Paracelsus Medical University, where they contribute significantly to advancing our understanding of tendon pathophysiology.

This project is already completed.