The regenerative capacity of well-preserved blood clots may be enhanced by biologics like enamel matrix derivative (EMD). This retrospective analysis compares outcomes reported by three centers using different heterografts. Center 1 (C1) treated intrabony defects combining cross-linked high-molecular-weight hyaluronic acid (xHyA) with a xenograft; center 2 (C2) used EMD with an allograft combination to graft a residual pocket. Center 3 (C3) combined xHyA with the placement of a resorbable polymer membrane for defect cover. Clinical parameters, BoP reduction, and radiographically observed defect fill at 12-month examination are reported. The 12-month evaluation yielded significant improvements in PPD and CAL at each center (p < 0.001, respectively). Analyses of Covariance revealed significant improvements in all parameters, and a significantly greater CAL gain was revealed for C2 vs. C1 (p = 0.006). Radiographic defect fill presented significantly higher scores for C2 and C3 vs. C1 (p = 0.003 and = 0.014; C2 vs. C3 p = 1.00). Gingival recession increased in C1 and C3 (p = 1.00), while C2 reported no GR after 12 months (C2:C1 p = 0.002; C2:C3 p = 0.005). BoP tendency and pocket closure rate shared similar rates. Within the limitations of the study, a data comparison indicated that xHyA showed a similar capacity to enhance the regenerative response, as known for EMD. Radiographic follow-up underlined xHyA’s unique role in new attachment formation.

Hyaluronic acid (HA) is a biologically active glycosaminoglycan with recognized roles in wound healing and inflammation modulation, and its adjunctive use in dental and periodontal therapy has gained interest, particularly in medically compromised patients. This narrative review critically evaluated preclinical and clinical evidence on locally applied HA in periodontal, oral surgical, peri-implant, and oral medicine treatments in patients with systemic conditions. A literature search of PubMed/MEDLINE, Scopus, and Web of Science (January 2015–December 2025) identified in vivo translational studies, randomized and controlled clinical trials, and selected systematic reviews involving medically compromised populations. Qualitative synthesis focused on biological plausibility, clinical outcomes, and safety. Nine core studies were included, comprising two preclinical in vivo investigations and seven clinical trials. In diabetic models, cross-linked high-molecular-weight HA reduced macrophage infiltration and delayed collagen membrane degradation without impairing angiogenesis. Clinically, adjunctive HA use in patients with type 2 diabetes mellitus was associated with modest but statistically significant short-term improvements in clinical attachment level (CAL) and enhanced early soft tissue healing following tooth extraction. In peri-implantitis therapy and oncology-related oral complications, HA application was linked to reduced inflammatory markers, decreased lesion severity, and improved patient-reported symptoms. No systemic adverse effects were reported. Overall, HA appears to be a locally safe adjunct that may support early healing and inflammation control in medically compromised patients, although its effects are primarily short-term and do not indicate disease-modifying potential.

Regenerative capacity of well-preserved blood clot may be enhanced by biologics like enamel matrix derivative (EMD). This retrospective analysis compares outcomes reported by three centers using different heterografts. Center 1 (C1) treated intrabony defects combining cross-linked heavy weight hyaluronic acid (xHyA) with a xenograft, Center 2 (C2) used EMD with an allograft combination to graft residual pocket. Center 3 (C3) combined xHyA with placement of resorbable polymer membrane for defect cover. Clinical parameters, BoP reduction and radiographically observed defect fill at 12-months examination are reported. The 12-months evaluation yielded significant improvement in PPD and CAL at each center (p<0.001, respectively). Analyses of Covariance revealed significant improvement of all parameters, significantly greater CAL gain disclosed C2 vs. C1 (p=0.006). Radiographic defect fill presented with significantly higher scores for C2 and C3 vs. C1 (P=.003 and =.014; C2 vs. C3 P=1.00). Gingival recession increased in C1 and C3 (P=1.00), while C2 reported no GR after 12-months (C2:C1 P=.002; C2:C3 P=.005). BoP tendency and pocket closure rate shared similar rates. Within limitations of the study, data comparison indicated that xHyA showed similar capacity to enhance regenerative response, as known for EMD. Radiographic follow-up underlined xHyA staying alone role in new attachment formation.