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Review Article • Acta Bras Cir 40 • 2025 • https://doi.org/10.1590/acb401825 linkcopy

Performance of blood concentrates in controlling inflammatory signs and symptoms after lower third molar extractions: an overview

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Purpose: To summarize the available evidence and answer the following question: What is the current knowledge on the performance of blood concentrates in handling sequelae after lower third molar extractions with the evidence available in systematic reviews?

Methods: An electronic search was conducted across nine databases. The study included systematic reviews with or without meta-analyses investigating the performance of blood concentrates in managing sequelae after lower third molar extractions. The four outcomes analyzed were pain, edema, mouth opening, and alveolar osteitis. The AMSTAR-2 tool assessed the methodological quality of the included systematic reviews, while ROBIS evaluated the risk of bias.

Results: The electronic search revealed 690 records, of which 15 were eligible systematic reviews for the present study. Overall, these reviews evaluated 75 primary studies published from 2007 to 2023. According to AMSTAR-2, only one systematic review presented high methodological quality. The ROBIS tool showed two systematic reviews with a low risk, and the others had a high risk of bias.

Conclusion: The current evidence is based on only one systematic review with high methodological quality and a low risk of bias, while the others exhibited a high risk of bias and low methodological quality. Therefore, the evidence regarding the efficacy of blood concentrates in controlling sequelae following lower third molar extractions is inconclusive.

Key words
Systematic Review; Inflammation; Platelet-Rich Fibrin; Platelet-Rich Plasma

Databases	Search strategies (June 2022) and Update (May 2024)
Primary databases
Cochrane Library https://www.cochranelibrary.com/	#1 «Molar, Third» OR «Wisdom Tooth» OR «Wisdom Teeth» OR «Third Molar» in All Text #2 «Pain, Postoperative» OR «Pain» OR «Edema» OR «Swelling» OR «Trismus» OR «Dry Socket» OR «Alveolar Osteitis» OR «Wound Healing» OR «Wound» OR «Healing» OR «Recovery» OR «Morbidity» OR «Outcomes» OR «Efficacy» OR «Comparison» in All Text #3 «Platelet-Rich Fibrin» OR «PRF» OR «Platelet-Rich» in All Text
Cochrane Library https://www.cochranelibrary.com/	#1 AND #2 AND #3
Embase https://www.embase.com	(‹molar, third›/exp OR ‹molar, third› OR ‹wisdom tooth›/exp OR ‹wisdom tooth› OR ‹wisdom teeth›/exp OR ‹wisdom teeth› OR ‹third molar›/exp OR ‹third molar›) AND (‹pain, postoperative›/exp OR ‹pain, postoperative› OR ‹pain›/exp OR ‹pain› OR ‹edema›/exp OR ‹edema› OR ‹swelling›/exp OR ‹swelling› OR ‹trismus›/exp OR ‹trismus› OR ‹dry socket›/exp OR ‹dry socket› OR ‹alveolar osteitis›/exp OR ‹alveolar osteitis› OR ‹wound healing›/exp OR ‹wound healing› OR ‹wound›/exp OR ‹wound› OR ‹healing›/exp OR ‹healing› OR ‹recovery›/exp OR ‹recovery› OR ‹morbidity›/exp OR ‹morbidity› OR ‹outcomes›/exp OR ‹outcomes› OR ‹efficacy›/exp OR ‹efficacy› OR ‹comparison›/exp OR ‹comparison›) AND (‹platelet-rich fibrin›/exp OR ‹platelet-rich fibrin› OR ‹prf› OR ‹platelet-rich›)
LILACS http://pesquisa.bvsalud.org/	((“Molar, Third” OR “Wisdom Tooth” OR “Wisdom Teeth” OR “Third Molar”) AND (“Pain, Postoperative” OR “Pain” OR “Edema” OR “Swelling” OR “Trismus” OR “Dry Socket” OR “Alveolar Osteitis” OR “Wound Healing” OR “Wound” OR “Healing” OR “Recovery” OR “Morbidity” OR “Outcomes” OR “Efficacy” OR “Comparison”) AND (“Platelet-Rich Fibrin” OR “PRF” OR “Platelet-Rich”)) AND ( db:(“LILACS”))
MEDLINE (via PubMed) http://www.ncbi.nlm.nih.gov/pubmed	#1 “Molar, Third”[Mesh] OR “Wisdom Tooth”[tw] OR “Wisdom Teeth”[tw] OR “Third Molar”[tw] #2 “Pain, Postoperative”[Mesh] OR “Pain”[Mesh] OR “Edema”[Mesh] OR “Swelling”[tw] OR “Trismus”[Mesh] OR “Dry Socket”[Mesh] OR “Alveolar Osteitis”[tw] OR “Wound Healing”[Mesh] OR “Wound”[tw] OR “Healing”[tw] OR “Recovery”[tw] OR “Morbidity”[Mesh] OR “Outcomes”[tw] OR “Efficacy”[tw] OR “Comparison”[tw] #3 “Platelet-Rich Fibrin”[Mesh] OR “PRF”[tw] OR “Platelet-Rich”[tw]
MEDLINE (via PubMed) http://www.ncbi.nlm.nih.gov/pubmed	#1 AND #2 AND #3
SciELO https://scielo.org/	((“Molar, Third” OR “Wisdom Tooth” OR “Wisdom Teeth” OR “Third Molar”) AND (“Pain, Postoperative” OR “Pain” OR “Edema” OR “Swelling” OR “Trismus” OR “Dry Socket” OR “Alveolar Osteitis” OR “Wound Healing” OR “Wound” OR “Healing” OR “Recovery” OR “Morbidity” OR “Outcomes” OR “Efficacy” OR “Comparison”) AND (“Platelet-Rich Fibrin” OR “PRF” OR “Platelet-Rich”))
Scopus http://www.scopus.com/	((“Molar, Third” OR “Wisdom Tooth” OR “Wisdom Teeth” OR “Third Molar”) AND (“Pain, Postoperative” OR “Pain” OR “Edema” OR “Swelling” OR “Trismus” OR “Dry Socket” OR “Alveolar Osteitis” OR “Wound Healing” OR “Wound” OR “Healing” OR “Recovery” OR “Morbidity” OR “Outcomes” OR “Efficacy” OR “Comparison”) AND (“Platelet-Rich Fibrin” OR “PRF” OR “Platelet-Rich”)
Web of Science http://apps.webofknowledge.com/	#1 TS=(“Molar, Third” OR “Wisdom Tooth” OR “Wisdom Teeth” OR “Third Molar”) #2 TS=(“Pain, Postoperative” OR “Pain” OR “Edema” OR “Swelling” OR “Trismus” OR “Dry Socket” OR “Alveolar Osteitis” OR “Wound Healing” OR “Wound” OR “Healing” OR “Recovery” OR “Morbidity” OR “Outcomes” OR “Efficacy” OR “Comparison”) #3 TS=(“Platelet-Rich Fibrin” OR “PRF” OR “Platelet-Rich”)
Web of Science http://apps.webofknowledge.com/	#1 AND #2 AND #3
Grey literature
EASY https://easy.dans.knaw.nl/	(«Third molar» OR «Platelet-Rich Fibrin» OR «PRF» OR «Platelet-Rich»)
MedRxiv https://www.medrxiv.org/	((«Molar, Third» OR «Wisdom Tooth» OR «Wisdom Teeth» OR «Third Molar») AND («Platelet-Rich Fibrin» OR «PRF» OR «Platelet-Rich»))

Authors, year journal	Objectives	Blood concentrate	Databases (Electronic search date)	Number of included primary studies		Risk of bias tool
Authors, year journal	Objectives	Blood concentrate	Databases (Electronic search date)	Qualitative synthesis	Quantitative synthesis	Risk of bias tool
Al-Hamed et al. (2017)²³ J Oral Maxillofac Surg	To assess the effect of PRF on socket healing after the surgical extraction of lower third molars.	PRF	Main databases: Cochrane Central Register of Controlled Trials; PubMed; Scopus. (August/November 2015)	6	- AO (n = 1) - BR (n = 2) - Trismus (n = 2)	Cochrane Collaboration tool
Bao et al. (2021)²⁷ J Oral Maxillofac Surg	To investigate the use of L-PRF and A-PRF for relieving signs and symptoms after lower third molar extraction.	A-PRF L-PRF	Main databases: Embase; PubMed; SinoMed; Web of Science. (October 2020)	10	- AO (n = 2) - Pain (n = 6) - WH (n = 4)	Cochrane Collaboration tool
Bao et al. (2021)²⁸ West China J Stomatol	To assess the efficacy of PRF in relieving complications after lower third molar extraction.	PRF	Main databases: Embase; PubMed; SinoMed; Web of Science. (February 2020)	21	- AC (n = 2) - AO (n = 3) - BR (n = 2) - Edema (n = 5) - Pain (n = 6) - Trismus (n = 2) - WH (n = 3)	Cochrane Collaboration tool
Barona-Dorado et al. (2014)¹⁵ Med Oral Patol Oral Cir Bucal	To assess the scientific evidence supporting PRP application in post-extraction sockets of retained lower third molars.	PRP	Main databases: Cochrane Central Register of Controlled Trials; Embase via Ovid; MEDLINE via PubMed; NIH. (June 2013)	3	Meta-analysis was not performed.	Jadad scale
Canellas et al. (2017)¹⁶ Int J Oral Maxillofac Surg	To assess potential differences in postoperative complications when using PRF in mandibular third molar surgeries.	PRF	Main databases: Cochrane Library; LILACS; MEDLINE via PubMed; ScienceDirect. Secondary databases: Theses and Dissertations Base (CAPES); Current Controlled Trials; ClinicalTrials.gov; EU Clinical Trials Register. (August 2016)	7	- AO (n = 2)	Cochrane Collaboration tool
Canellas et al. (2019)²⁵ Int J Oral Maxillofac Surg	To assess to which indications PRF has been effective in oral surgical procedures.	PRF	Main databases: Cochrane Library; LILACS; MEDLINE via PubMed; Scopus; Web of Science. Secondary databases: ClinicalTrials.gov; EU Clinical Trials Register. (September 2017)	30	- AO (n = 3) - BR (n = 2) - BRMSL (n = 2) - DIS (n = 2) - Edema (n = 3) - Pain (n = 6)	Cochrane Collaboration tool
Costa et al. (2023)³² Clin Oral Investig	To evaluate the effectiveness of different blood concentrates in controlling inflammatory signs and symptoms after lower third molars extractions.	PRP A-PRF L-PRF CGF	Main databases: Cochrane Library; Web of Science; Embase; MEDLINE via PubMed; Scopus; Lilacs; SciELO. Secondary databases: OpenGrey; MedRxiv. (March 2022 / May 2023)	36	- Pain (n = 18) - Trismus (n = 5)	Cochrane Collaboration tool
Fujioka-Kobayashi et al. (2021)¹⁷ J Oral Maxillofac Surg Med Pathol	To investigate the efficacy of PRF in handling lower third molar extractions from randomized clinical trials.	PRF	Main databases: Cochrane Central Register of Controlled Trials; Embase; LILACS; MEDLINE via PubMed; Scopus. Secondary databases: Grey Literature Report; OpenGrey. (June 2020)	18	- AO (n = 5)	RoB 2
He et al. (2017)²⁴ J Oral Maxillofac Surg	To analyze the local PRF application to control postoperative signs and symptoms after extracting an impacted lower third molar.	PRF	Main databases: Cochrane Library; Embase; PubMed; Web of Science. (October 2016)	10	- AO (n = 4) - BR (n = 2) - Edema (n = 3) - Pain (n = 6) - Trismus (n = 3)	Cochrane Collaboration tool
Ramos et al. (2022)³⁰ J Oral Maxillofac Surg	To determine whether different platelet aggregation protocols (PRF/L-PRF and A-PRF) have similar effects on pain, edema, and trismus control.	PRF A-PRF L-PRF	Main databases: Cochrane; Embase; MEDLINE; PubMed; BVS; Web of Science. (April/July 2021)	17	- Edema (n = 5) - Pain (n = 7) - Trismus (n = 5) - WH (n = 5)	Cochrane Collaboration tool
Ribeiro et al. (2024)³³ Clin Oral Investig	L-PRF		Main databases: Cochrane Library; Web of Science; Embase; MEDLINE via PubMed; Scopus. (December 2023)	5	Meta-analysis was not performed.	Cochrane Collaboration tool
Snopek et al. (2022)³¹ Oral Surg	PRF		Main databases: Cochrane Library; Embase; MEDLINE via PubMed; Scopus; Web of Science. Secondary databases: ClinicalTrials.gov; Grey Literature Report; OpenGrey. (June 2020)	6	- Pain (n = 3)	Cochrane Collaboration tool
Vitenson et al. (2022)¹⁸ Int J Oral Maxillofac Surg	A-PRF L-PRF		Main databases: Cochrane Library; Embase; MEDLINE via PubMed; Scopus. Secondary databases: OpenGrey; OpenThesis. (December 2020)	4	- Edema (n = 3) - Pain (n = 3) - Trismus (n = 3)	Cochrane Collaboration tool
Xiang et al. (2019)²⁶ BMC Oral Health	PRF		Main databases: Cochrane Library; Embase; PubMed. (September 2017)	10	- AO (n = 3) - BR (n = 2) - Edema (n = 4) - Pain (n = 6) - Trismus (n = 4) - WH (n = 2)	Cochrane Collaboration tool
Zhu et al. (2021)²⁹ Int J Oral Maxillofac Surg	PRF		Main databases: Cochrane Library; Embase; PubMed; Web of Science. (May 2019)	19	- AO (n = 6) - Pain (n = 13) - Trismus (n = 3) - WH (n = 4)	Cochrane Collaboration tool

Authors, year	Main results	Main conclusions
Al-Hamed et al. (2017)²³	PRF showed overall positive results for pain, trismus, edema, periodontal pocket depth, soft tissue healing, and localized osteitis incidence. The meta-analysis could not be performed for all variables. The meta-analyses did not show significant benefits for PRF compared to natural healing sockets.	Considering the limitations of the available evidence, PRF does not seem beneficial for bone consolidation after lower third molar extractions. Further controlled and standardized randomized clinical trials are required to estimate the effect of PRF on socket regeneration.
Bao et al. (2021)²⁷	A-PRF showed a better effect among the three groups for the improvement of postoperative pain on the third and seventh days. L-PRF promoted soft tissue healing on the seventh day compared to the control. However, other comparisons did not show significant differences.	Limited results showed that applying A-PRF after third molar extraction reduced postoperative pain, and L-PRF promoted soft tissue healing on the seventh postoperative day. However, the positive impact on other postoperative sequelae was not confirmed. Further large-scale randomized controlled trials with uniformly standardized measuring methods are required to improve the analyses.
Bao et al. (2021)²⁸	PRF showed significant positive effects on pain, edema, soft tissue healing, trismus, and alveolar osteitis. There was no statistically significant effect on bone healing.	Limited clinical evidence indicates that applying PRF after lower third molar extraction may reduce pain, edema, trismus, and dry socket alveolitis and promote soft tissue healing. However, the effect of PRF on bone healing requires further large-scale randomized controlled trials with uniform measuring criteria.
Barona-Dorado et al., (2014)¹⁵	Gürbüzer et al., 2008: No statistically significant differences. Rutkowski et al., 2010: PRP showed significantly smaller facial edema and higher bone density. Haraji et al., 2012: PRP showed significantly lower post operative pain, improved healing, and lower postoperative alveolar osteitis incidence.	The scientific evidence for using PRP in third-molar surgeries is scarce. Hence, randomized clinical trials are required before recommending the clinical application of PRP.
Canellas et al. (2017)¹⁶	PRF seemed to accelerate healing in mandibular third molar surgeries, reducing postoperative pain and edema. PRF significantly decreased alveolar osteitis prevalence.	Although further well-designed clinical trials with larger samples are required to allow definitive conclusions, PRF is a potentially suitable biomaterial.
Canellas et al. (2019)²⁵	PRF showed significantly better bone regeneration for alveolar cleft reconstruction, decreased alveolar osteitis prevalence, and increased implant stability one week and one month after surgery.	PRF may present improved wound healing when used in oral surgical procedures. The most consistent indications of this systematic review are to preserve alveolar dimensions after extraction and to reduce alveolitis incidence after lower third molar surgery.
Costa et al. (2023)³²	A-PRF and L-PRF resulted in lower pain levels on the first and third postoperative days compared to the blood clot. On the seventh postoperative day, pain was significantly lower for A-PRF, L-PRF, and PRP compared to the blood clot. There was a statistically smaller difference in the reduction of interincisal opening for A-PRF compared to L-PRF and the blood clot during the acute inflammatory period. A-PRF, L-PRF, PRP, and CGF demonstrated favorable outcomes in reducing edema in at least one evaluated period.	Given the low quality of evidence, A-PRF following lower third molar extractions demonstrated superior performance among the analyzed blood concentrates and appeared effective in reducing postoperative pain at all evaluated time points. Trismus decreased with the use of A-PRF during the peak inflammatory period.
Fujioka-Kobayashi et al. (2021)¹⁷	PRF significantly reduced the alveolar osteitis rate from 15.9% in the control group to 5.8% in the PRF group, representing an approximated three-fold reduction. PRF showed better results for soft tissue healing.	PRF decreases postoperative pain/morbidity, favors soft tissue healing, and presents lower complication rates of alveolar osteitis. Therefore, PRF represents a feasible auxiliary treatment after lower third molar removal.
He et al. (2017)²⁷	PRF significantly relieved pain, reduced edema on the third postoperative day, and decreased alveolar osteitis incidence. There were no significant differences in swelling on the first postoperative and bone consolidation day.	The local application of PRF after lower third molar extraction is a valid method to relieve pain and edema at three postoperative days and reduce alveolar osteitis incidence. For patients subjected to complicated surgical extractions, PRF may be recommended for local socket applications.
Ramos et al. (2022)³⁰	L-PRF showed better pocket depth, insertion level, and pain control (first and third days), but it was not associated with improved soft tissue healing on the seventh day. A-PRF presented lower analgesics intake. L-PRF and A-PRF controlled edema better but not trismus.	Using L-PRF and A-PRF allows better pain and edema c ontrol than standard PRF protocols, but none affected trismus. PRF and L-PRF protocols improved soft tissue healing but not to a statistically significant degree. However, they improved probe depth in the third month after the third molar surgery.
Ribeiro et al. (2024)³⁶	Using L-PRF contributed to reduce postoperative pain and discomfort.	The L-PRF considerably reduced postoperative pain, edema, alveolar osteitis incidence, and infections following third molar removal surgery compared to patients not subjected to L-PRF application.
Snopek et al. (2022)³¹	PRF favored the reduction of alveolar osteitis frequency and had an uncertain effect on the level of postoperative pain, edema, and wound healing. Pain levels did not show statistical differences.	Considering the low number of included studies, the effect of PRF after lower third molar surgery could not be evaluated. Further studies should focus on a higher methodological quality to produce reliable and comparable study results.
Vitenson et al. (2022)¹⁸	A-PRF caused significantly lower pain scores than L-PRF and natural wound healing after two, three, and seven days. A-PRF had a significant effect on facial edema and trismus and some positive effects on soft tissue healing.	The included studies were characterized by considerable heterogeneity and confounding variables. Thus, the level of evidence seems inadequate for clinical recommendations according to the focus question.
Xiang et al. (2019)²⁶	PRF relieved pain and edema and reduced alveolar osteitis incidence. There was no statistical difference for trismus and bone and soft tissue healing.	PRF reduces only some postoperative complications, but it does not prevent all of them. PRF significantly relieved pain and edema and reduced alveolar osteitis incidence after extracting an impacted lower third molar.
Zhu et al. (2021)²⁹	PRF significantly reduced alveolar osteitis incidence and postoperative pain (first, third, and seventh days) compared to the controls.	Besides reducing alveolar osteitis incidence and postoperative pain after third molar surgery, it may also improve postoperative healing of soft tissues.

Authors, year	Questions																Methodological quality
Authors, year	1	2^ critical domain.	3	4^ critical domain.	5	6	7^ critical domain.	8	9^ critical domain.	10	11	12	13^ critical domain.	14	15^ critical domain.	16	Methodological quality
Al-Hamed et al. (2017)²³	N	N	N	PY	N	Y	Y	Y	Y	N	N	N	N	Y	N	Y	Critically low
Bao et al. (2021)²⁷	Y	N	N	PY	Y	Y	N	PY	Y	N	Y	N	N	Y	N	Y	Critically low
Bao et al. (2021)²⁸	Y	N	N	PY	N	Y	N	Y	Y	N	Y	N	N	Y	N	Y	Critically low
Barona-Dorado et al., (2014)¹⁵	Y	N	N	PY	N	N	Y	PY	PY	N	NM	NM	Y	Y	NM	N	Low
Canellas et al. (2017)¹⁶	Y	Y	N	Y	Y	N	Y	Y	Y	N	N	N	Y	Y	N	Y	Low
Canellas et al. (2019)²⁵	Y	Y	N	Y	Y	N	Y	Y	Y	N	N	N	Y	Y	N	Y	Low
Costa et al. (2023)³²	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	High
Fujioka-Kobayashi et al. (2021)¹⁷	Y	PY	N	Y	Y	Y	Y	Y	Y	N	Y	N	N	Y	N	Y	Critically low
He et al. (2017)²⁷	N	N	N	PY	N	Y	N	Y	Y	N	Y	N	N	Y	Y	Y	Critically low
Ramos et al. (2022)³⁰	Y	Y	N	PY	Y	Y	Y	Y	Y	N	Y	N	N	Y	N	Y	Critically low
Ribeiro et al. (2024)³⁶	Y	Y	Y	Y	Y	N	N	Y	Y	Y	NM	NM	Y	N	NM	N	Low
Snopek et al. (2022)³¹	Y	Y	N	Y	Y	Y	Y	Y	Y	N	Y	Y	Y	Y	N	Y	Low
Vitenson et al. (2022)¹⁸	Y	Y	N	Y	Y	N	Y	Y	Y	N	Y	Y	Y	Y	N	Y	Low
Xiang et al. (2019)²⁶	Y	N	N	PY	Y	Y	N	PY	Y	N	Y	N	N	Y	N	Y	Critically low
Zhu et al. (2021)²⁹	Y	N	N	PY	Y	Y	N	Y	Y	N	Y	N	N	Y	N	Y	Critically low

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