Table 3 Intervention and outcomes of included studies

Cvek et al. [23]

C: extraction; extra-alveolar storage; replantation;

E: additional systemic application of doxycycline

Doxycycline, 4 mg/kg intravenously at the time of anesthesia, approximately 20 min before extraction and, 2 mg/kg intramuscularly for 5 consecutive days after replantation

Hematoxylin–eosin stain, modified Gram stain, modified Mallory stain;

the presence and amount of vital tissue, occurrence of inflammatory changes and presence of bacteria in the pulpal lumen

The prophylactic, systemic treatment with doxycycline had no effect on the frequency of pulp revascularization nor on the occurrence of inflammatory changes

Sae-Lim et al. [25]

C: pulp infection; hemisected; extraction; 5 mm fissure of the buccal or lingual mid-roots were shaved; replantation

E: additional systemic application of tetracycline hydrochloride

Tetracycline hydrochloride, 20 mg/kg orally, on the day of extraction/replantation and for the following 6 days, three times a day

Hematoxylin–eosin stain;

the appearance of the root surface was evaluated and classified as healed or showing the presence of inflammatory root resorption

Significantly more complete healing and less inflammatory root resorption in tetracycline group than the control

group

Sae-Lim et al. [26]

C: extraction; extra-alveolar storage; replantation;

E: additional systemic application of tetracycline hydrochloride

Tetracycline hydrochloride, 20 mg/kg, orally, immediately after replantation and for the following 6 days, three times a day

Hematoxylin–eosin stain;

the appearance of the root surface was evaluated and classified as healed or showing the presence of replacement or inflammatory root resorption

Complete healing for the tetracycline was much higher than the control group, but it was not statistically different

Cvek et al. [24]

C: extraction; extra-alveolar storage; replantation;

E: immersion in doxycycline for 5 min before replantation

1 mg doxycycline in 20 ml sterile physiologic saline

Hematoxylin–eosin stain, modified Gram stain;

the presence and amount of vital tissue, occurrence of inflammatory changes and presence of bacteria in the pulpal lumen

Increased frequency of complete pulp revascularization and decreased frequency of micro-organisms in the pulpal lumen, ankylosis and inflammatory root resorption was observed in the doxycycline group

Yanpiset et al. [29]

C: extraction; extra-alveolar storage; replantation;

E: immersion in doxycycline for 5 min before replantation

1 mg doxycycline in 20 ml saline

Radiographic evaluation and hematoxylin–eosin stain;

assessment of the presence/absence

of vital pulp tissue above the cervical margin of the tooth

Soaking for 5 min in doxycycline significantly increased the revascularization rate

Ma et al. [27]

C: endodontically treated; extraction; extra-alveolar storage; replantation;

E: rinse with 5 ml saline and soaked in 1 ml 50 mg/ml minocycline for 5 min before replantation

Minocycline, 50 mg/ml

Hematoxylin–eosin stain;

evaluation of the periodontal healing as healing, inflammatory resorption, or replacement resorption

Topical application of minocycline increased occurrence of complete healing slightly, but the difference was not statistically signifiant

Ritter et al. [28]

C: extraction; extra-alveolar storage; immersion in saline for 5 min; replantation;

E: covered with minocycline hydrochloride microspheres for 5 min or soaked in doxycycline solution for 5 min before replantation

Covered with minocycline hydrochloride microsphere or soaked in doxycycline solution

Post-replantation radiographs 6 days after replantation, laser Doppler 7, 15, 25, 35, 45, 60 days after replantation, and H&E evaluation after sacrifice;

Pulp revascularization

Minocycline-treated specimens presented a significantly higher number of vital teeth than saline-treated specimens. The number of vital teeth in doxycycline-treated specimens was higher than saline-treated specimens, but no statistical significance was observed

Bryson et al. [34]

C: instrumented; filled with gutta percha; hemisected; extracted; dried; replanted without minocycline

E: coated with minocycline and then replanted

Coated with minocycline, no mention about the concentration

Hematoxylin–eosin stain;

extent of root resorption and type of interface between the root and surrounding tissue (Favorable Healing, or Unfavorable Healing)

Teeth treated with minocycline exhibited no significant difference in the amount of favorable healing and the average remaining root structure when compared to those treated without minocycline

Chen et al. [21]

C: hemisected; extracted; filled with Gutta–Percha and sealer (AH plus); 60 min dry time; replanted;

E: filled 3% Demeclocycline before 60 min dry time

3% Demeclocycline

Hematoxylin–eosin stain;

the extent of root resorption and the type of interface between the root and surrounding tissue (Favorable Healing, or Unfavorable Healing)

the groups treated with Tetracycline had statistically significantly more favorable healing and more remaining root structure than the group filled with Gutta–Percha replanted after 60 min dry time

Gomes et al. [32]

C: extracted; dried for 60 min; removed the dental papilla; extirpated the pulp tissue through the apical foramen; removed the root surface-adhered PDL; filled the root canals with a calcium hydroxide–saline paste; sealed; replanted;

E: additional systemic application of tetracycline

Tetracycline, 2.5 mg/kg, oral gavage, at 12-h intervals, for 7 days after tooth replantation

Hematoxylin–eosin stain; site of epithelial reattachment, PDL organization, intensity and extent of the acute and chronic inflammatory process at the site of epithelial reattachment and PDL, root resorption (active or inactive, extent, depth and repair), bone tissue, and ankylosis

Systemic antibiotic therapy has a positive influence on the repair process in delayed tooth replantation, but it was not statistically different

Melo et al. [33]

C: extracted; immersed in saline for 5 min and replanted

E: additional systemic application of tetracycline

Intragastric administration of tetracycline, 2.5 mg/kg, 12/12 h, for 7 days after tooth replantation

Hematoxylin–eosin stain; site of epithelial reattachment, PDL organization, intensity and extent of the acute and chronic inflammatory process at the site of epithelial reattachment and PDL, root resorption (active or inactive, extent, depth and repair), bone tissue, and ankyloses

Systemic antibiotic therapy presented a positive effect in the immediate tooth replantation repair process, contributing to a better pulpal and PDL repair, but it was not statistically different

Bjorvatn et al. [36]

C: extracted; dry for 45 min and replanted

E: immersed in doxycycline for 5 min, rinsed with saline before replantation

1% solution of doxycycline

Hematoxylin–eosin stain; the presence of uncomplicated healing, surface resorption, inflammatory resorption, replacement resorption (ankylosis), and inflammatory reaction in the absence of resorption

The application of doxycycline to the root surface had results similar with the control group

Selvig et al. [35]

C: extracted; root-planted; dry for 45 min and replanted

E: immersed in tetracycline HCl for 5 min before replantation

1% solution of tetracycline HCl

Hematoxylin–eosin stain; the presence of surface resorption, inflammatory resorption, ankylosis, or inflammatory reaction in the absence of resorption

In control group, periodontal healing was characterized by massive ankylosis and inflammatory resorption. Experimental group showed great variation in healing response. Four teeth showed normal healing, whereas the remaining four teeth showed various amounts of inflammatory resorption, ankylosis, and persisting inflammation in the absence of resorption or ankylosis

Liu et al. [50]

C: immersed in saline for 5 min before replantation

E: immersed in doxycycline for 5 min before replantation

0.05 mg/mL doxycycline

Clinical observation of the avulsed teeth

Compared with treatment with normal saline, avulsed permanent teeth treated with doxycycline did not show a better clinical outcome

Nam et al. [51]

C: extraction; dry for 5 min or preserved in HBSS for 60 min; saline irrigation for 10 s; replantation

E: extraction; dry for 5 min or preserved in HBSS for 60 min; saline irrigation for 10 s; 5 min soaking in doxycycline before replantation; replantation

1 mg doxycycline in 20 ml saline

Micro-CT and hematoxylin–eosin stain; the presence of periapical radiolucency feature, the severity of root resorption

Pulpal healing in the doxycycline group was comparable with the control group. And the doxycycline group showed no improvement in periodontal healing after 5 min of dry storage, but exhibited a lower a lower grade of surface root resorption and inflammatory resorption in the teeth stored for 60 min in HBSS