Laminin-1 Peptide Conjugated Fibrin Hydrogels Restores Salivary Gland Function

Objectives: Salivary gland damage caused by blunt injury, chemotherapy and radiotherapy leads to hyposalivation. Hyposalivation can lead to severe consequences in the patient’s health, and affects their quality of life. However, current treatments for hyposalivation are limited to medications or artificial saliva, which provide only temporary relief. Therefore, alternative therapies (safe and effective) are highly needed to restore salivary gland function. A promising option for the treatment of salivary gland regeneration is bioengineered scaffolds. Previous studies demonstrated that the laminin-111 protein is critical for intact salivary gland cell cluster formation and organization. However, a complete laminin-111 protein is not suitable for clinical applications as each protein domain may contribute to adverse side effects including degradation, tumorigenesis and immune responses. Conversely, the use of synthetic peptides can minimize the immune reactivity or pathogen transfer. Moreover, it is relatively simple, inexpensive and safe as compared to animal-derived proteins. Therefore, the goal of this study was to demonstrate whether treatment with laminin-111-derived peptide conjugated fibrin hydrogel (L_1p-FH) promotes tissue regeneration in submandibular glands (SMG) of a wound healing mouse model.
Methods: Surgical wounds were made in the mSMG, followed by application of L_1p-FH. After 8 or 20 days, glands were removed, sectioned and stained for histopathological analysis. Furthermore, quality of saliva, body weight changes and cellular atypia were determined.
Results: L_1p-FH applied to wounded SMG produced the following effects: a) formed well-differentiated acinar and ductal structures, b) formed capillaries and neurons, c) improved quality of salivary protein patterns (especially mucins and proline rich proteins) and d) enhanced body weight to levels comparable to sham controls. Moreover, L_1p-FH treated mSMG wounds showed no differences in proliferation rates and lack of evidence for cellular atypia.
Conclusions: In summary, L_1p-FH facilitated salivary gland tissue healing. The regenerated gland tissues displayed structural and functional restoration with an absence of cellular atypia.