## 1 Introduction  
Systemic sclerosis (SSc) is a complex multisystem disease of autoimmune origin defined by excessive collagen deposits by pathologic fibroblasts [1] and consecutive fibrosis of the skin and internal organs and by hyper-reactivity and obliteration of the microvasculature [2], which induce general and oral handicaps [3]. SSc has been associated with impaired oral health, including periodontal problems. SSc patients have increased periodontal indicators (deep periodontal pockets, plaque deposits, and bleeding on probing) when compared to controls [4; 5; 6]. SSc patients can also be at increased risk to develop periodontal pathologies due to xerostomia and impaired oral hygiene consecutive to reduced manual dexterity and mouth opening, the use of immunosuppressive drugs [7], as well as periodontal morphopathological changes associated with the systemic disease [8; 9]. Mesenchymal stromal cells (MSCs) are important players participating in the complex network of exchange involved in tissue and organ regeneration and homeostasis [10]. Bone marrow MSCs from SSc were shown to display differentiation impairments, a loss in angiogenic potential based on the diminished capability to induce endothelial precursors [11], increased expression of senescent markers [11; 12], and a modified microRNAs (miRNAs) expression profile relevant for cell abnormalities [12], while maintaining immunosuppressive and immune-regulatory functions [11]. Other studies reported more consistent functional properties of bone marrow MSCs from SSc in comparison to MSCs from healthy patients [13; 14]. Due to potential yet insufficiently validated abnormalities of oral MSCs in SSc patients that may hamper periodontal regeneration, the use of biomaterials with a stimulating effect on local progenitors as adjuvant of periodontal therapies appears to be of particular interest. To our knowledge, oral MSCs have not been isolated and characterized from SSc, nor has their functionality been evaluated. Moreover, no reports are available concerning their behavior in relation to biomaterials used in periodontal practice. Hyaluronan is a natural low-molecular-weight glycosaminoglycan identified in different fluids of the organism and an essential ingredient of the extracellular matrix of mineralized and non-mineralized tissues such as periodontal components [15]. Hyaluronan is more abundant in the gingiva and in the periodontal ligament than in the alveolar bone and cement [16]. The term hyaluron is used to refer to both forms of this molecule (acid--hyaluronic acid HA or salt--sodium or potassium hyaluronate) [16]. It is also important to acknowledge that hyaluron has bacteriostatic and fungistatic effects [17; 18], as well as anti-inflammatory, anti-oedematous [19], osteoinductive [20; 21], pro-angiogenic [22], and wound-healing-promoting properties [23]. Although no firm recommendations on hyaluron periodontal clinical indications have been developed, the product was used in periodonology as an adjunctive product to nonsurgical and/or surgical therapies to diminish inflammation and induce healing [16; 24]. Based on the above-mentioned properties, HA could be used as an adjunctive biomaterial to stimulate repair and regeneration after periodontal procedures. Complex treatments based on HA associated with adipose tissue-derived MSCs have already been provided to aid the management of complex lesions in SSc patients [14]. Although more clinical studies reporting on the clinical benefices of HA need to be conducted, it is essential to first improve information on the effect of this molecule on the behavior of oral progenitor cells implicated in periodontal healing after periodontal therapies. Further studies are required to isolate and gain insights into the capacities of oral MSCs to sustain periodontal regeneration in SSc. Against this backdrop, the aim of this in vitro study was to provide the first comprehensive characterization of two oral lines of MSCs isolated from SSc and to assess their functionality in comparison to MSCs from a healthy patient.