The influence of direct laser metal sintering implants on the early stages of osseointegration in diabetic mini-pigs

Naiwen Tan, Xiangwei Liu, Yanhui Cai, Sijia Zhang, Bo Jian, Yuchao Zhou, Xiaoru Xu, Shuai Ren, Hongbo Wei, Yingliang Song

Full text link : https://pubmed.ncbi.nlm.nih.gov/28814861/

The influence of direct laser metal sintering implants on the early stages of osseointegration in diabetic mini-pigs

1. Scientific Reference

• Study Title: The influence of direct laser metal sintering implants on the early stages of osseointegration in diabetic mini-pigs
• Authors: Naiwen Tan, Xiangwei Liu, Yanhui Cai, Sijia Zhang, Bo Jian, Yuchao Zhou, Xiaoru Xu, Shuai Ren, Hongbo Wei, Yingliang Song
• Journal: International Journal of Nanomedicine
• Year of Publication: 2017
• DOI: 10.2147/IJN.S138615

2. Scientific Background

Achieving predictable osseointegration remains one of the fundamental objectives of dental implant therapy. This challenge becomes particularly relevant in patients with diabetes mellitus, where impaired wound healing, chronic inflammation, and altered bone metabolism may negatively affect implant integration and long-term stability.

Previous research has highlighted the increased risk of implant complications and delayed osseointegration in diabetic individuals. As a result, considerable attention has been directed toward implant surface modifications capable of enhancing biological responses during the early healing phase.

Direct Laser Metal Sintering (DLMS) represents an advanced additive manufacturing technology that enables the creation of highly porous and interconnected titanium implant surfaces. Such architectures may provide a more favorable environment for cell attachment, osteoblast activity, and bone formation. Within the field of implant dentistry and oral rehabilitation, understanding whether these surface characteristics can compensate for biologically compromised conditions is of significant clinical interest.

This study explores the biological performance of DLMS implant surfaces in a diabetic animal model and investigates their potential influence on early osseointegration.

3. Study Objective

The primary objective of this study was to determine whether dental implants manufactured using Direct Laser Metal Sintering technology could improve osseointegration in a diabetic environment.

The investigators also sought to compare cellular behavior, osteogenic gene expression, radiographic bone parameters, and histological bone-to-implant integration between DLMS implants and implants treated with Micro Arc Oxidation (MAO).

4. Methodology

This was a preclinical experimental study combining both in vitro and animal investigations.

Two implant surface technologies were evaluated:

• Direct Laser Metal Sintering (DLMS)
• Micro Arc Oxidation (MAO)

In vitro experiments involved MG63 osteoblast-like cells cultured on both implant surfaces. Cell morphology and the expression of osteogenesis-related genes, including collagen (COL), RUNX2, and alkaline phosphatase (ALP), were assessed.

For the in vivo phase, diabetes was induced in six mini-pigs using streptozotocin. A total of 36 implants were placed in the mandibular premolar regions. Twenty-four implants featured DLMS surfaces, while twelve implants served as MAO controls.

Osseointegration was evaluated after 3 and 6 months using:

• Micro-computed tomography (micro-CT)
• Histological assessment with Van Gieson staining
• Bone-to-implant contact (BIC) measurements

5. Main Findings

Surface characterization demonstrated a substantial difference in roughness between the two implant designs. The average roughness (Ra) measured 27.4 ± 1.1 μm for DLMS implants compared with 2.3 ± 0.3 μm for MAO implants.

Cellular analysis revealed enhanced spreading on the DLMS surface. Cells exhibited more abundant filopodia and lamellipodia, indicating stronger interaction with the porous three-dimensional architecture.

Gene expression analyses showed generally higher osteogenic activity on DLMS surfaces. Among the evaluated markers, collagen expression was significantly greater after ten days of osteogenic induction.

Micro-CT evaluation demonstrated improved peri-implant bone formation around DLMS implants at three months. Significant differences favoring DLMS were observed for bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp).

Histological findings supported these observations. At three months, bone-to-implant contact reached 33.2% ± 11.2% in the DLMS group compared with 18.9% ± 7.3% in the MAO group.

At six months, both implant types showed further bone maturation, and the differences between groups were no longer statistically significant. Bone-to-implant contact values reached 42.8% ± 10.1% for DLMS implants and 38.3% ± 10.8% for MAO implants.

6. Clinical Analysis

Rather than demonstrating a completely different biological outcome, this study suggests that DLMS technology may influence the speed at which osseointegration develops under diabetic conditions.

The highly porous and interconnected surface architecture appears to create a favorable environment for cellular attachment and mechanical anchorage. Enhanced cell spreading observed in vitro may facilitate the early biological events required for successful bone healing around implants.

From a clinical perspective, this observation is particularly relevant because diabetes is known to interfere with the early phases of peri-implant bone formation. Accelerating initial osseointegration could theoretically contribute to improved implant stability during the critical healing period.

However, the study also highlights an important nuance. While DLMS implants demonstrated superior performance during the early healing phase, the differences diminished over time. By six months, both implant types achieved comparable levels of osseointegration.

Consequently, the findings should not be interpreted as evidence that DLMS implants ultimately achieve higher long-term integration than conventional surfaces. Instead, the data suggest a potential advantage in promoting earlier bone response in a biologically compromised environment.

As with all animal studies, caution is required before extrapolating these results directly to clinical implant treatment in human patients.

7. Clinical Applications

The findings may be relevant in several areas of implant dentistry and oral rehabilitation, including:

• Implant treatment in patients with diabetes mellitus.
• Development of implant surfaces designed to enhance early healing.
• Research on additive manufacturing technologies for dental implants.
• Optimization of implant design for medically compromised patients.
• Investigation of strategies aimed at improving early implant stability.

The study may also contribute to future developments in personalized implant manufacturing and advanced implant surface engineering.

8. Level of Evidence, Limitations and Transparency

This publication represents a preclinical study combining laboratory experiments and an animal model.

As such, its level of evidence is lower than that provided by randomized clinical trials, systematic reviews, or meta-analyses. The results offer valuable biological insights but do not establish definitive clinical recommendations.

Several limitations should be considered:

• Use of an animal model rather than human subjects.
• Small sample size involving six mini-pigs.
• Absence of long-term clinical outcomes in humans.
• Follow-up limited to six months.

The authors reported no conflicts of interest related to this work. Funding was provided by the National Natural Science Foundation of China.

9. Key Study Highlights

• Study Type: Preclinical study (in vitro and animal research)
• Level of Evidence: Preclinical evidence
• Study Population: Six diabetic mini-pigs
• Number of Implants: 36 implants
• Follow-up Duration: 3 and 6 months
• Primary Outcome: Osseointegration around dental implants
• Main Finding: DLMS implants demonstrated enhanced early osseointegration compared with MAO implants
• Scientific Conclusion: Highly porous DLMS surfaces may accelerate early bone integration under diabetic conditions
• Potential Limitations: Animal model, limited sample size, lack of human clinical validation

10. Scientific Impact

This study contributes to the growing body of research evaluating additive manufacturing technologies in implant dentistry. Its principal contribution lies in demonstrating that implant surface architecture may influence biological responses during the early stages of healing, even in a metabolically compromised environment.

The findings support the concept that highly porous titanium structures can facilitate cellular attachment and bone formation. This is particularly important in the context of diabetes, where impaired healing mechanisms may jeopardize implant success.

From a research perspective, the study provides experimental evidence supporting further investigation of laser-manufactured implant surfaces. It also reinforces the broader hypothesis that implant surface design is a critical determinant of the bone–implant interface.

Although clinical confirmation remains necessary, these results help establish a biological rationale for future human studies evaluating advanced implant surface technologies in high-risk patient populations.

11. Editorial Conclusion

This preclinical investigation suggests that Direct Laser Metal Sintering may enhance the early phases of osseointegration in a diabetic environment by promoting favorable cellular interactions and faster peri-implant bone formation. While the observed advantages were most evident during the initial healing period and became less pronounced over time, the study provides valuable insights into the role of implant surface architecture in compromised biological conditions. Further clinical research is required before these findings can be translated into routine implant treatment protocols.