Abstract:
Introduction: Lymphedema (LE) is a chronic and progressive disease caused by damage to lymphatic
vessels and/or lymph nodes (LNs). Conservative treatment includes complex decongestive therapy,
physiotherapy, exercise, and skin care, while surgical treatment options include lymphovenous
anastomosis, vascularized LN transfer, and reductive procedures such as liposuction and excisional
techniques. Although these approaches provide symptomatic relief, they do not restore damaged
lymphatic structures. Lymphatic tissue engineering (LTE) represents a promising regenerative
strategy, combining biomaterials, scaffolds, cells, growth factors, and in vitro and in vivo models to
promote the regeneration of lymphatic structures.
Materials and methods: This work is based on a literature review in LTE and presents our experience
in LNs-based TE. The literature review focused on current strategies in LTE, with an emphasis on LNs
decellularization, decellularized scaffold, lymphatic endothelial cell culture, and preclinical animal
models. Articles were selected from PubMed, Google Scholar, and Scopus, without time restrictions.
Our experience at the Laboratory of Tissue Engineering and Cell Culture involves decellularization
method applied to nonvascularized lymph nodes (NLNs) in small animal models, assessing their
potential for regenerative applications.
Results: Anatomical studies of the lymphatic system in small animal models (rats) were performed to
identify suitable models for LN-based TE. Among the LN examined, the axillary LN was found to be
the most practical and accessible for experimental procedures. A low-concentration detergent protocol
was developed for decellularization of NLNs. This protocol allowed effective removal of cellular
components while preserving the extracellular matrix architecture, providing a suitable scaffold for
potential regenerative applications, as demonstrated in our previous experience. The literature review
revealed that similar approaches have been explored in other preclinical models, showing that
decellularization and decellularized scaffold-based strategies can preserve LN microarchitecture and
support regenerative applications.
Conclusion: (i) Axillary LN in small animal models are practical for LN-based TE; (ii) Lowconcentration detergent decellularization preserves extracellular matrix structure, providing scaffolds
for regenerative applications; (iii) Preclinical studies support these strategies, highlighting their
potential to promote lymphatic regeneration and improve treatments for lymphedema.
Funding. This research was supported by grants from Project No. 25.80012.8007.03TC within the
Young Researchers Project Competition 2025–2026, Chisinau, Republic of Moldova.
