Post-cystectomy bone regeneration: the challenge of residual defects

Surgical enucleation of maxillary or mandibular cystic lesions frequently leaves medium to large-sized bone defects. These substance losses can compromise the structural integrity of the jaws, delay functional rehabilitation, and complicate future implant placement. While autografting remains the "gold standard", its drawbacks — donor site morbidity and limited availability — prompt practitioners to seek biostimulating therapies capable of amplifying endogenous regenerative processes.

Objective and hypotheses of the translational study

Photobiomodulation (PBM) is proposed as a non-invasive intraoperative adjuvant to modulate osteogenic activity. However, the majority of current evidence is based on animal models or immortalized cell lines, which do not reflect human biological complexity. This study therefore evaluates the effect of a 980 nm PBM protocol (20 J; 40 J/cm²) on human cortical bone explants harvested from 40 patients during cystectomies.

The precise objective was to measure the impact of irradiation on the abundance of osteoblast-like cells, morphometric results, and cell viability. The authors test the hypothesis that a 980 nm laser can stimulate early osteogenic activity and the differentiation of resident progenitors directly within the native tissue microenvironment, without altering cell survival.

Methodology: an ex vivo translational model

This comparative ex vivo translational study was conducted on cortical bone explants harvested from 40 patients undergoing enucleation of medium to large-sized maxillary or mandibular cysts. Ultimately, viable primary cultures were established for 34 patients (experimental yield of 85%).

The experimental design was based on a split-sample comparison for each patient:

• PBM Group: immediate exposure after curettage to a 980 nm pulsed laser (total energy: 20 J; fluence: 40 J/cm²).
• Control Group: matched native explant, non-irradiated.

The explants were cultured using a primary outgrowth technique with osteogenic induction over a 14-day period. To evaluate the biological response of human bone to the laser, the authors used:

• Morphometric analysis and imaging: immunofluorescence labeling of alkaline phosphatase (ALPL) and osteocalcin (OCN), analyzed by confocal microscopy.
• Cellular evaluation: count of osteoblastic cells and measurement of viability by live/dead fluorescence test.
• Statistical analysis: data were processed using the Wilcoxon test for paired series.

A marked acceleration of ex vivo osteogenic activity

Of the 40 patients initially included, viable cultures were successfully established for 34 of them, representing an experimental yield of 85%. Quantitative morphometric analysis reveals a clear and statistically significant superiority of the group treated with 980 nm photobiomodulation (PBM) compared to the control group after 14 days of induction.

The increase in cell count (nearly double compared to the control) highlights the biostimulating effect of the laser protocol on the recruitment or proliferation of progenitors derived from the cortical explant.

Qualitative observations and differentiation markers

Confocal microscopy immunofluorescence analysis allowed for the evaluation of the maturity of the produced cells. The results show:

• Enzymatic expression: A qualitatively stronger intensity of alkaline phosphatase (ALPL) in PBM-treated cultures, a sign of increased early osteoblastic activity.
• Mineralization: A more marked expression of osteocalcin (OCN), confirming a more advanced terminal differentiation of cells towards a mineralized matrix-secreting phenotype.

Cell viability: a safe protocol

A critical point of the study concerned the safety of 980 nm pulsed irradiation (20 J total). The live/dead fluorescence test revealed no significant difference in cell viability between irradiated explants and controls (Wilcoxon test, p = 0.18). The thermal or photonic energy input therefore induced no detectable cytotoxicity, validating the biological safety of this setting (40 J/cm²) on fresh human bone tissue.

Analysis of results and clinical relevance

The data from this ex vivo study reveal that the intraoperative application of a 980 nm laser (40 J/cm²) acts as a catalyst for primary osteogenesis. The nearly doubled increase in the number of osteoblastic cells (median of 2820 compared to 1525 in the control group) and osteoblastic surface occupancy (19.00% vs 11.75%) suggests an immediate metabolic activation of resident progenitor cells. Clinically, this biostimulation could reduce the latency phase observed after the enucleation of large cysts, thereby facilitating faster stabilization of the bone defect.

Strengths and limitations of the study

The major strength lies in the use of fresh human cortical bone explants, bypassing the usual biases of immortalized cell lines (such as MG-63) or animal models. This translational approach provides a more accurate picture of the tissue response in the dental office. However, the model presents inherent limitations due to its ex vivo design: the absence of a functional vascular network, systemic immune response, and mechanical loading limits the direct extrapolation of long-term healing kinetics. Furthermore, although the yield is high (85%), the influence of individual patient variations on the response to PBM warrants further investigation.

Comparison and perspectives

While the literature often relies on wavelengths in the visible red, this study confirms the interest of near-infrared (980 nm) for its penetration capacity into mineralized tissues. The safety of the protocol is confirmed by the absence of difference in cell viability between the groups (p = 0.18), validating a non-thermal setting (20 J in total).

Summary of results

The intraoperative application of a 980 nm laser (40 J/cm²) on human alveolar bone explants significantly increases early osteogenic activity. The study reports a near-doubling of the number of osteoblastic cells (median: 2820 versus 1525; p < 0.001) and increased expression of ALPL and OCN markers, all without compromising cell viability.

In concrete terms, for the practitioner:

• Optimize socket healing: Integrate photobiomodulation (PBM) immediately after cystic enucleation to stimulate resident bone progenitors of the cortical wall.
• Clinical settings: A 980 nm pulsed protocol delivering 20 J in total (fluence of 40 J/cm²) increases osteoblast surface occupancy from 11.75% to 19%.
• Biological safety: Use these parameters with confidence to promote regeneration; fluorescence tests confirm that the treatment induces no local cell mortality.

Technical lexicon of the study

Photobiomodulation (PBM): Use of non-thermal light energy (here a 980 nm laser) to modulate cellular metabolism and biological signaling pathways, influencing tissue proliferation and differentiation.

Maxillary bone explants: Human cortical tissue samples collected during surgery, allowing the ex vivo study of osteogenic responses while preserving native interactions between cells and the extracellular matrix.

Alkaline phosphatase (ALPL): Membrane enzyme used in this study as an immunofluorescence marker to evaluate early osteogenic activity and the differentiation of osteoblast-like cells.

Osteocalcin (OCN): Non-collagenous protein secreted by osteoblasts, serving as a specific marker to identify mature bone formation and mineralization within cultures.

Fluence: Energy dose delivered per unit area, expressed here in J/cm² (40 J/cm²), a critical parameter determining the efficacy of the laser biostimulation protocol.

Outgrowth technique: Primary culture method consisting of inducing the migration and proliferation of resident cells (osteoprogenitors) from a tissue fragment (the explant) into the culture medium.

Cystectomy: Surgical procedure consisting of the excision of a cystic lesion of the jaws, creating a bone defect whose regeneration can be stimulated by adjuvant agents.

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