Osseointegration is vital to success in orthopedic and dental reconstructions with implanted materials. The bone matrix or cells—particularly osteoblasts—are required to achieve functional contact on the implant surface. Osteoblast induction is therefore essential for osteogenesis to occur. Enhancement of osteoblast adhesion, proliferation, and differentiation, particularly by implant surface modifications, have been found challenging to develop. Secretory Leukocyte Protease Inhibitor (SLPI), a cation ionic protein with anti-inflammatory and anti-bacterial activities, showed activation in osteoblast proliferation and differentiation. However, the effects of coating recombinant human (rh) SLPI on a titanium alloy surface on human osteoblast adhesion, proliferation, and differentiation has never been investigated. In this study, titanium alloys (Ti–6Al–4V) were coated with rhSLPI, while human osteoblast adhesion, proliferation, differentiation, actin cytoskeletal organization, and gene expressions involved in cell adhesion and differentiation were investigated. The results indicate that coating titanium with 10–100 µg/ml rhSLPI enhanced the physical properties of the Ti surface and enhanced human osteoblast (hFOB 1.19) cell adhesion, activated actin dynamic, enhanced adhesive forces, upregulated integrins α1, α2, and α5, enhanced cell proliferation, mineralization, alkaline phosphatase activity, and upregulated ALP, OCN, and Runx2. This is the first study to demonstrate that coating SLPI on titanium surfaces enhances osseointegration and could be a candidate molecule for surface modification in medical implants.

Inflammation is a crucial defence mechanism against infections and harmful stimuli. However, uncontrolled inflammation can lead to low-grade inflammatory conditions that disrupt tissues and systemic function. Anti-inflammatories relieve symptoms. However, it can cause side effects and lack targeted control. These limitations are addressed by “peptide-based therapeutics.” The secretory leukocyte protease inhibitor (SLPI) has anti-inflammatory effects. However, SLPI has a short half-life and low cellular uptake. Using short peptides is a promising therapeutic strategy due to their small size, high effectiveness, and low immunogenicity. This research investigates the anti-inflammatory effect of SLPI-derived short peptides (SDSPs). SLPI was enzymatically digested in silico to produce SDSPs. The physiological properties of SDSPs and their anti-inflammatory activities in an LPS-induced RAW 264.7 cell inflammatory model were examined. Digested fragments, including 11 from pepsin (P1-11) and 9 from trypsin (T1-T9) digestion, plus the N-terminal fragment, were obtained. SDSPs are diverse physiological properties, and some are anti-inflammatory peptides (AIPs). Determination in the LPS-induced macrophage inflammation model found four potential SDSPs, specifically T6, T7, T8, and P7, exhibit anti-inflammatory properties by reducing excessive ROS generation and the activation of the MAPK/NF-κB pathway, similar to SLPI. This study identifies possible candidates for anti-inflammatory medicines warranting further investigation in in vivo and clinical trials for inflammation-related disorders.

The clinical success rate of titanium (Ti) implants is significantly reduced in elderly patients and by implant-associated bacterial infections. Thus, Ti surfaces were modified using sandblasted large-grit alkaline etching (SLA), argon-nonthermal plasma treatment, and recombinant human secretory leukocyte protease inhibitor (rhSLPI) coating. This study evaluated surface characteristics, human fetal osteoblast (hFOB 1.19) activities, and antibacterial efficacy. The modified surfaces exhibited increased roughness and hydrophilicity compared to Ti. The SBPTi-rhSLPI enhanced 7-day protein retention on the surface. While Ti promoted higher cell proliferation, the modified groups demonstrated superior cell adhesion and mineralization. Specifically, SBPTi-rhSLPI showed the highest cytoplasmic spreading, adhesion-related gene expression (Itg$\alpha$1, Itg$\alpha$2, Itg$\alpha$5, and Itg$\beta$1), and mineralization. Additionally, rhSLPI-coated groups effectively reduced the adhesion of both S. aureus and E. coli. In conclusion, combining SLA modification, argon plasma treatment, and rhSLPI coating provides enhanced effects. This combined approach significantly enhances osteoblast adhesion and mineralization while possessing antibacterial potential, which could be a promising strategy to improve implant success rates.

Secretory Leukocyte Protease Inhibitor (SLPI), a protein functions as an anti-inflammatory molecule that maintains the protease-antiprotease balance. Although SLPI is gaining recognition as a potential biomarker, additional research is required to connect its levels with existing indicators and the quick Sepsis-related Organ Failure Assessment (qSOFA) score to determine its therapeutic value. This study included 50 patients with sepsis and 50 healthy controls recruited from Uttaradit Hospital. Plasma SLPI concentrations were assessed utilising a quantitative ELISA, and the results were compared with standard indicators including Procalcitonin (PCT), C-reactive protein (CRP), lactate, and white blood cell (WBC) count. The findings indicated that plasma SLPI concentrations were markedly increased in the sepsis group relative to healthy controls. ROC curve study of diagnostic accuracy revealed that PCT and CRP had the highest discriminative efficacy, while SLPI also proved to be a meaningful indicator. SLPI had a substantial moderate positive connection with the qSOFA score, in addition to CRP, PCT, and WBC count. A significant association was not observed between SLPI and lactate levels, indicating that SLPI is indicative of systemic inflammation and organ failure rather than direct metabolic distress. In conclusion, plasma SLPI could be a sepsis biomarker that corresponds with severity and inflammatory markers. The moderate association between SLPI and qSOFA scores suggests its possible application in monitoring organ dysfunction in septic patients. Traditional markers like PCT and CRP are reliable for initial diagnosis, but SLPI's unique regulatory capabilities may help diagnose and treat sepsis-related organ damage.