Effects of Minocycline on Early Wound Healing after Implant Placement: An In Vitro and Randomized Clinical Study

ABSTRACT Objective To determine the in vitro effects of minocycline on human gingival fibroblasts (HGFs), its clinical impact on early wound healing after implant placement, and its potential mechanism of action. Methods First, we evaluated the in vitro proliferation, migration, and collagen production of HGFs treated with different concentrations of minocycline, as well as the underlying mechanism. Subsequently, we conducted a clinical trial and randomly assigned 40 partially edentulous patients to either the test (minocycline hydrochloride treatment) or control (blank control) group immediately after implant surgery. The early wound healing score (EHS), pain index, gingival index (GI), modified sulcus bleeding index (mSBI), and peri‐implant crevicular fluid samples were assessed or collected 3 and/or 7 days after surgery. Results In vitro, 1 μg/mL minocycline promoted the proliferation, migration, and collagen production of HGFs. Minocycline inhibited collagen degradation by downregulating the expression of matrix metalloproteinase‐2 (MMP‐2) and MMP‐14 and upregulating tissue inhibitors of metalloproteinases‐2. However, higher concentrations of minocycline, 10 and 100 μg/mL, exhibited adverse effects. In the randomised clinical trial, the test group showed significantly better clinical outcomes compared to the control group, with higher EHS and lower GI, mSBI, concentrations of IL‐1β, IL‐10, and TNF‐α, and relative abundance of Streptococcus and gram‐negative anaerobic bacteria. Conclusions Small doses of minocycline (1 μg/mL) promoted the proliferation and migration of HGFs and inhibited collagen degradation in vitro. Locally delivered minocycline after implant surgery improves clinical outcomes by promoting early wound healing, relieving the inflammatory response, and decreasing early colonisation of gram‐negative anaerobic bacteria. Trial Registration This clinical trial was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2100044680)