Topical oxygen therapy as a novel strategy to promote wound healing and control the bacteria in implantology, oral surgery and periodontology: A review

Abstract

Globally, oral infections and inflammatory lesions persist as substantial public health concerns, necessitating the introduction of novel oral treatment protocols. Oral diseases are linked to various causative factors, with dental plaque/biofilm resulting from inadequate hygiene practices playing a predominant role. The strategic implementation of novel topical therapies holds promise for effectively controlling the biofilms, addressing oral infections and promoting enhanced oral wound healing. This review aims to providing a comprehensive overview of the available evidence pertaining to the potential efficacy of topical oxygen and lactoferrin-releasing biomaterials, exemplified by the blue®m formula, as novel oral care interventions within the scope of contemporary implantology, oral surgery and periodontology.

Keywords: Biomaterials; Oral biofilm; Oral care; Oxygen therapy; Peri-implantitis; Periodontitis.

Fig. 1

History of > 100 years to understand the ‘etiologic factors’ of periodontal diseases.

Fig. 2

Image of large CHX molecule structure compare to small oxygen (O2) molecule.

Fig. 3

Scheme of the TOOTh directive for oral healthcare.

Fig. 4

Illustration of microbial homeostasis in oral biofilm (Symbiosis vs Dysbiosis).

Fig. 5

Aggressive periodontitis in a 36-year-old female patient. In the initial panoramic x-ray, notable bone loss is evident, particularly around the areas of teeth 26, 27, and 28.

Fig. 6

In the provided clinical images: (A) illustrates the initial clinical situation, revealing bleeding on probing, probing depths exceeding 5 mm, and clinical attachment loss surpassing 40 %. A diagnosis of generalized aggressive periodontitis was made. The treatment protocol consisted of extraction of 26, 27, and 28 due to the severity of the bone loss, and non-surgical periodontal therapy combined with blue®m oxygen therapy for the rest of the dentition. (B) depicts supra and subgingival scaling and root planing, followed by the application of blue®m gel. The gel was meticulously introduced into the periodontal pockets and around the teeth. (C) shows the immediate effect of the gel application, with observable bubbles indicating the topical release of oxygen. (D) provides a closer view of the bubbles, confirming the oxygen release. Subsequent images include (E) one day post-therapy using blue®m gel and (F) the second application of blue®m gel.

Fig. 7

In the provided clinical images: (A) illustrates the status two days post-therapy using blue®m gel. (B) illustrates the third application of blue®m gel. (C) displays the condition three days post-therapy. Subsequent follow-up assessments are represented by (D) after fifteen days, (E) after thirty days, and (F) after sixty days. The periodontal tissues exhibited a healthy status throughout these follow-up periods, characterized by the absence of bleeding on probing, reduced probing depths ranging from 1 to 4 mm, and excellent plaque control.

Fig. 8

Five-year recall. Clinical views (A, B) and panoramic x-ray (C) reveal significant progress. The patient had undergone orthodontic treatment and lower arch rehabilitation with two implants. Notably, periodontal tissues exhibited a healthy status, characterized by the absence of bleeding on probing, reduced probing depths, and excellent plaque control.

Fig. 9

Peri-implant mucositis. In the provided clinical images: (A) illustrates the initial clinical appearance of peri-implant tissues following the removal of the prosthesis, revealing signs of gingival inflammation and bleeding on probing. Probing depths measured between 2 to 4 mm, prompting a diagnosis of peri-implant mucositis. (B) showcases the application of blue®m gel, carefully spread across the inflamed region. Notably, the images capture the release of oxygen bubbles upon gel application. (C) presents the follow-up evaluation conducted after 48 h, tracking the progress of treatment. (D) exhibits the follow-up assessment after 7 days, revealing a notable improvement with a healthy appearance of the peri-implant tissues, indicating successful management of peri-implant mucositis.

Fig. 10

Application of blue®m gel whenever fitting healing abutments (stock or customised) and implant restorations.

Fig. 11

Early implant placement in a 43-year-old healthy female patient. Clinical view four weeks after the “atraumatic” extraction of the lower right second premolar (A). A customized anatomical healing abutment (Cervico, VP Innovato Holdings Ltd, Cyprus) was fabricated. Blue®m gel was placed on the prosthetic screw and the subgingival part of the abutment (B). The customized abutment was immediately fitted onto the implant at implant placement appointment, and the flap was sutured tension-free around the healing abutment using 5–0 monofilament sutures (C). Application of blue®m gel immediately post-op and twice a day during the healing period (D). Clinical picture 3 months post-op (E). The unique anatomy of the anatomical healing abutment facilitated proper oral hygiene measures by the patient during the healing phase. This, in synergy with the daily local application of the oxygen and lactoferrin-releasing blue®m gel, allowed the patient to maintain the abutment free of plaque, and enhanced the healing process of the peri-implant tissues (F, G). Application of blue®m gel onto the implant platform and the peri-implant soft-tissues prior fitting the final restoration (H). Clinical view immediately after the instalment of the implant crown (I).

Fig. 12

Peri-implantitis in a 58-year-old male patient with non-contributory medical history. In the provided clinical images: (A, B) illustrate the initial clinical situation, revealing pus discharge on palpation, bleeding on probing, probing depths exceeding 8 mm, and bone loss affecting the implant #12. A diagnosis of localized peri-implantitis was made. The treatment protocol consisted of initial conservative therapy combined with application of blue®m gel with an interdental brush twice a day for six months (C), followed by surgical therapy.

Fig. 13

Surgical approach six months after the conservative treatment. A site-specific full-thickness flap was raised and all inflammatory soft-tissues were thoroughly removed using sharp curettes and degranulation burrs (A). The exposed implant surfaces were cleaned with titanium brushes (B) and then polished (C). Subsequently, blue®m gel was topically applied for 5 mins to hydrate the bone and release oxygen and lactoferrin in the area, in an attempt to decontaminate the implant surfaces and the surrounding tissues, and to enhance the healing (D). After removing the gel and rinsing with sterile saline, guided bone regeneration was performed using a synthetic bone substitute (E) and the flap was repositioned and sutured using 5–0 PTFE sutures (F). Blue®m gel was applied immediately post-operatively and provided to the patient to use twice a day during the healing period (G).

Fig. 14

Follow-up assessment after 3 months, revealing significant improvement with healthy peri-implant soft tissues without swelling, nor bleeding on probing (A), and reduced probing depths ranging from 3 to 4 mm (B). Periapical x-ray showing notable bone gain at the crestal level of the implant #12 (C).

Fig. 15

Clinical pictures illustrating a fresh extraction socket (A). The removal of all soft tissues (B) is essential for successful healing. (C) Topical application for 5 mins of blue®m gel, followed by rising with sterile saline, can assist the decontamination of the site. (D) Clinical view 2 weeks post-operatively revealing the healthy granulation tissue inside the socket and newly-formed connective tissue and epithelium at the periphery of the wound.

Fig. 16

Oxygen and lactoferrin can be also used (A) in the forms of foam (B) or solution (C, D) for the treatment of fresh extraction sockets.

Fig. 17

Clinical images showing the uneventful open healing of grafted sockets (A). Six days post-operatively the graft is embedded in a fibrin matrix (B) and the topical application of oxygen and lactoferrin (C) twice a day during the healing period may enhance the production of new collagen and epithelium to promote the healing by secondary intention, and at the same time to control the bacteria, minimizing the risk for post-operative infection. (D) Three months post-operatively the alveolar ridge preservation procedure preserved the volume of the ridge and the grafted area is covered by newly-formed keratinized soft tissues. (E) The bone grafting resulted in the regeneration of adequate amount of hard tissues to facilitate the correct placement of dental implants.

Fig. 18

(A) Wound dehiscence one week after implant placement of two implants and simultaneous guided bone regeneration in the upper anterior area. Incomplete closure of the wound with no signs of infection. The surgical site was treated with blue®m gel to address the wound dehiscence and promote the secondary intention healing of the area (B). To facilitate the application of the blue®m gel, the patient was instructed to apply it twice a day on the inner surface of the provisional partial denture, ensuring that the gel will stay for adequate time in contact with the healing tissues. The denture was inspected to ensure that no pressure was applied on the alveolar ridge (C, D). Three months later, excellent healing of the area is observed. The ridge is completely covered by healthy keratinised soft tissues (E).

Fig. 19

Controlling the bacteria that accumulate on the sutures and promoting the healing of the incision lines is essential for uneventful healing and for limiting the risk for infection, wound dehiscence and scar formation. A semilunar flap was sutured using 5–0 PTFE sutures (A). Application of blue®m gel immediately post-op and twice a day during the healing period (B, C). Clinical result after six days at suture removal (D), seven months post-operatively (E) and four years post-operatively (F).

Fig. 20

Management of an impacted mandibular third molar with associated cystic lesion in a healthy 27-year-old male patient. Initial clinical view (A). The CBCT is showing the #48 in direct contact to the distal aspect of the distal root of the adjacent second molar, and the cystic lesion buccally to the roots of the impacted third molar (B, C). A full-thickness flap was raised (D) and subsequently bone was removed to expose the impacted #48, which was sectioned and removed in pieces. The cystic lesion (E) was enucleated in toto (F). The histopathological findings were consistent with a dentigerous cyst.

Fig. 21

The site was thoroughly debrided of all soft tissues (A), and blue®m gel was applied for 5 mins and then rinsed with sterile saline (B). Subsequently, the bone defect was grafted using an injectable fully-resorbable synthetic bone substitute (C) and the flap was repositioned and sutured using 5–0 monofilament sutures (D). Blue®m gel was applied immediately post-operatively and provided to the patient to use twice a day during the healing period (E). (F, G) illustrate the clinical result eight months post-op. Adequate reconstruction of the soft and hard tissue topography and no residual periodontal pockets distally to the second molar.

Fig. 22

Comparative CBCT images of the patient before (A, B) and eight months post-operatively (C, D). The treatment resulted in the regeneration of new bone and the reconstruction of the anatomy and architecture of the ridge.