Table 2.

Summary of major clinical studies.

Population	Intervention	Study design	Key findings	Limitations	Key references
14 healthy participants	Acupuncture was applied at specific points used in the treatment of spinal cord injury.	interventional study	Acupuncture significantly decreased BDNF and MMP-9 levels in peripheral blood.	small sample size and lack of clinical outcomes related to spinal cord injury.	Moldenhauer et al. (2010)
21 patients with Guillain-Barré syndrome	Plasma MMP-9 levels	observational correlation study	Higher plasma MMP-9 levels were associated with demyelination and peripheral nerve dysfunction in Guillain-Barré syndrome.	small sample size and lack of causal inference.	Sharshar et al. (2002)
86 patients with refractory diabetic dermal ulcers	Patients received either standard wound care or standard care plus topical application of autologous platelet-rich gel (APG).	randomized controlled trial	Topical APG significantly reduced ulcer area and improved proteolytic balance by lowering MMPs and increasing TIMP-1.	lacks long-term follow-up and detailed analysis of systemic effects.	He et al. (2012)
33 patients with chronic diabetic foot lesions (UT stage 2a)	Patients received either standard wound care or standard care plus daily application of ORC/collagen protease-inhibiting matrix.	interventional study	The ORC/collagen matrix reduced the MMP-9/TIMP-2 ratio	small sample size and short follow-up duration limited to 8 days	Lobmann et al. (2006)
12 patients with non-healing diabetic foot ulcers	Participants were randomized to receive non-contact low-frequency ultrasound (NCLF-US) either three times or once per week, or no ultrasound treatment.	prospective randomized clinical trial	Thrice-weekly NCLF-US treatment significantly reduced wound area and was associated with decreased MMP-9, pro-inflammatory cytokines and improved healing.	small sample size, limiting the generalizability of the results	Yao et al. (2014)
24 patients with diabetic foot ulcers	Topical propolis was applied to diabetic foot ulcers	Controlled Clinical Trial	Topical propolis significantly improved ulcer healing rates and reduced bacterial load and MMP-9 activity compared to controls.	small sample size, single-center design, and use of a non-randomized control group.	Henshaw et al. (2014)