The effect of Xenograft and Platelet-Rich Plasma in the surgical management of Intra bony Defects

in periodontitis patients: A Systematic Review

Abstract:
Background: When treating intrabony defects to regenerate periodontal structure, platelet rich plasma
alone or in conjuction with various grafting material, enamel matrix protien, and barrier membrane have
shown promising results.
Aim: This evidence based review aimed to systematically appraise the efficacy of Xenograft in
combination with PRP in the surgical treatment of periodontal intrabony defects in comparison to
Xenograft alone in terms of clinical and radiographic outcomes in adults with periodontitis.
Methods: Electronic and mannual data were searched exhaustively by two reviewers, including PubMed-
Medline, Cochrane Central Register of Controlled Trials, Embase and Scopus from the earliest available
date till 31 January 2023 without restriction on language. Randomized controlled clinical trials (RCTs) of
either parallel or of a split-mouth design and studies where Xenograft and platelet rich plasma (PRP) were
in the intervention group or as a comparator were included.
Results: After screening the articles, three studies were included. The current systematic review reveals
that PRP used as an adjunct with a xenograft resulted in a significant reduction in pocket depth (PD) and
greater clinical attachment level (CAL) gain in comparison to Xenograft alone.
Conclusion: The analysis of present review conclude that PRP in conjuction with xenograft for treatment
of intrabony defects shows promising outcomes. However, owing to the short follow-up time and
heterogenity of included studies, caution should be followed while employing this material clinically.
Keywords: Xenograft, platelet-rich plasma, periodontal disease, periodontitis, intra-bony defects
 1. Introduction

Periodontal disease is exemplified as irreversible damage to the connective tissue and the loss of
attachment of alveolar bone. This disease continues to progress if no intervention is planned, leading to
tooth loss. Contemporary treatment modalities to restore the periodontium have shown the limited
potential to obtain the desired result. [1] Preserving the healthy and functional state of natural dentition is
the goal of periodontal treatment. The key factor to restoring the periodontium is stimulating a cascade of
tissue regeneration by activating the series of healing events. This process will eventually result in the
establishment of integrated tissue formation. [2] The modulators utilized during this process are growth
and attachment factors, extracellular matrix, and morphogenetic proteins. [3] Recent research focuses on
applying polypeptide growth factors (PGFs) in periodontal tissue regeneration [4]. The transforming
growth and platelet-derived growth factors (PDGF) are the most significantly researched concerning
periodontal regeneration among the PGFs. These constituents are known to promote bone regeneration
following bone grafting by stimulating stem cell proliferation, neoangiogenesis, cellular chemotaxis, and
mitosis, as well as increasing osteoconduction through the fibrin network. [5] The current focus of the
periodontal treatment modality is to utilize platelet-rich plasma (PRP) in reducing intrabony defects. The
PRP is an autologous source of TGF-β, and PDGF is platelet-rich plasma (PRP) obtained by isolating and
concentrating platelet via gradient density centrifugation. This technique concentrates the platelet with
33.8% of identified TGF-β and PDGF within the concentrate. Research has confirmed that using PRP as
an agent for a periodontal wound increases the concentration of growth factor locally, thus enhancing the
healing outcome. Apart from using PRP in various medical fields, it has also been used successfully in
guided bone regeneration, as a graft in maxillary sinus to assist in accommodating dental implants, and to
improve the clinical outcome of subepithelial connective tissue graft procedures. [6] Studies on PRP have
analyzed that while preparing PRP for treatment, this material exhibits "sticky consistency," which
eventually improves graft material's clinical properties, thereby enhancing periodontium healing [7-12].

Periodontist utilizes various surgical and non-surgical procedures to regenerate the lost periodontium. The
most common surgical procedure utilized for intrabony defects includes treatment ethier alone with open
flap debridement (OFD) or in conjunction to demineralized freeze-dried bone allograft, autogenous bone,
or freeze-dried bone, and guided tissue regeneration. [7] Another treatment option for periodontal
debridement is bone grafts, including allografts, xenografts, autografts, and alloplasts. Xenograft is a
recently introduced bone graft material and a research subject of interest. These organic bones are
customized by removing all proteinaceous cells and materials, leaving behind a scaffolding of inert
absorbable bone, over which the expected osteoblast migration, revascularization, and woven bone
formation occur. [8]

Recent systematic reviews [13,14] have demonstrated the efficacy of PRP as a treatment modality for
intra-bony defects. However, due to the heterogeneity in results and methodology of included studies, it
was difficult to draw a conclusive remark. Moreover, the first-ever published systematic review
established evidence of the beneficial effect of PRP on treating periodontal defects [15]. Contrasting
results were obtained from the data collected by a convectional review on clinical effect of PRP alone or
in conjunction with various bioactive materials. The authors of this review suggested that systematic
reviews should focus on combining PRP with different graft materials to produce evidence-based results.

To the author's knowledge, no systematic review has focused on the efficacy of PRP and xenograft
material in treating intra bony periodontal defects. As a result, it is not clear whether the addition of PRP
to various bioactive materials, especially Xenograft, could increase PRP's efficacy in treating intrabony
defects compared to Xenograft alone as an agent. Therefore, this systematic review aims to evaluate the
efficacy of PRP in combination with Xenograft compared to Xenograft alone in treating periodontal bony
defects (clinically and radiographically).

2. Materials and Methods

This systematic review was established in accordance to the Preferred Reporting Items for Systematic
Reviews and Meta-Analyses (PRISMA) statement guidelines and the Cochrane Handbook [6,7]. The
protocol for the study was developed and registerd on the International Prospective Register of
Systematic Reviews PROSPERO (Reg. No: CRD42023397860) before the commencement.
Focused Question
How does Xenograft, combined with PRP compared to Xenograft alone, impact the regeneration of
periodontal intrabony defects in terms of clinical and radiographic outcomes in adults with periodontitis?
To address current systematic review objectives, PICOS (Participants, Interventions, Comparisons,
Outcomes) is outlined in Table 1.
Table 1: PICOS (Participants, Interventions, Comparisons, Outcomes)

Participants Adult population (≥18 years) with chronic periodontitis patients

Interventions Patients receiving Xenograft with PRP

 Comparisons Patients receiving Xenograft only

Outcomes Bone regeneration was assessed by probing pocket depth (PPD), clinical attachment level (CAL) and
bone fill radiographically.

Search Strategy
Electronic and mannual data were searched exhaustively by two reviewers, including PubMed-Medline,
Cochrane Central Register of Controlled Trials, Embase and Scopus from the earliest available date till 31
January 2023 without restriction on language. Additional sources were explored like google scholar,
MedIND, conference proceedings, and cross-references. Researchers explored emerging research
registries such Clinical Trial Registry India, Cochrane Oral Health Group Trials Register, and National
Institutes of Health Trials. For any unpublished studies, the authors were contacted. To maintain a
thorough screening procedure, a manual search of periodontology-related journals was carried out,
including the Journal of Dental Research, Journal of Clinical Periodontology, Journal of Periodontology,
and The International Journal of Periodontics & Restorative Dentistry. In attempt to discover research that
matched all inclusion criteria, references in the articles that were eliminated were also checked. A detailed
search strategy was given in Table 2 and tailored to each database when necessary.

Table 2: Search Strategy in PubMed

Domains Keywords
Sr. No. Wildcard
(Periodontal Loss, Periodontal Attachment)
OR (Alveolar Process Atroph*) OR
(Alveolar Resorption*) OR (Resorption*,
Alveolar) OR (Bone Loss*, Periodontal) OR atrophy,
(Periodontal Bone Loss*) OR (Periodontal atrophies,
Resorption) OR (Resorption, Periodontal) resorption,
OR (Alveolar Bone Atroph*) OR (Bone resorptions,
Atroph*, Alveolar) OR (Bone Loss*, loss, losses,
Alveolar) OR (Intra-bony Defects) OR (Bony bone, bony,
defect*) OR (Defect*, bony) OR (Bone defect,
1 Periodontitis defect*) OR (Defect*, bone) defects
(Regeneration, Periodontal Guided Tissue)
OR (Guided Periodontal Tissue
Regeneration) OR (Periodontal Guided
Tissue Regeneration) OR (guided bone
regeneration) OR (GTR) OR (GBR)
2 Regenerative surgery
(Heterograft) OR (Xenografts) OR
(Xenograft) OR (bovine) OR (porcine) OR
(anorganic bovine bone mineral) OR
(ABBM)
3 Xenografts
(Plasma, Platelet-Rich) OR (Platelet Rich
4 PRP Plasma) OR (PRP) OR (prp)
 (Outcome, Treatment) OR (Patient-Relevant
Outcome) OR (Outcome*, Patient-Relevant)
OR (Patient Relevant Outcome*) OR
(Clinical Effectiveness) OR (Effectiveness,
Clinical) OR (Treatment Effectiveness) OR
(Effectiveness, Treatment) OR
(Rehabilitation Outcome) OR (Outcome, outcome,
5 Treatment outcome Rehabilitation) OR (Treatment Efficacy) outcomes
*Indicates wildcard in PubMed

Eligibility criteria
Articles were considered for inclusion if they fulfilled the following criteria:
1. Split mouth or parallel designed randomized control trials.
2. Studies in which PRP and Xenograft were used as the intervention group;
3. studies where Xenograft alone served as a comparative.
4. articles with a follow-up period of at least six months;
5. studies on patients over the age of 18 who had infrabony deformities and were clinically
diagnosed with periodontitis.
The exclusion criteria included the following:
1. Articles where patients' systemic conditions or abnormal platelet counts could have an impact on the
effectiveness of periodontal treatment.
2. studies that employed additional bone grafting materials;
3. have used a biological sample that would not make a significant comparisons; and
4. Reviews, case studies, and animal studies were excluded.
Outcome Variables
The difference in CAL between the initial diagnosis and the completed follow-up was author's main
outcome variable for trials evaluating the impact of Xenograft combined with PRP in treating intrabony
deformities. The secondary outcome variable was the difference in probing pocket depth (PPD) between
the baseline and the last follow-up.
Screening and selection
Researchers digitally scanned all titles and abstracts into the Excel screening spreadsheet after importing
all search results into EndNote 20. The papers were initially read by the title and abstract by two
reviewers independently. The search excluded any reviews, analyses, or clinical trials. If the search terms
appeared in the title and abstract, the papers were chosen for full-text reading. Additionally, papers
lacking abstracts that had titles that suggested to their relevance to the review's goals were chosen for
eligibility screening on the full text. Two reviewers carefully examined the full-text papers. Data
extraction was carried out on the papers that met the criteria for selection. Two reviewers contemplated
all of the included studies' references lists to find any more relevant literature. Evaluators discussed the
findings and if there was a conflict, a third evaluator was contacted and his decision was considered to be
final.
Data extraction
A standardized tabulated form was used to extract the relevant data by two reviewers and was verfied by
third reviewer. Authors discussed and resloved the conflicts. For each included study, the resulting data
were extracted: author and year of publication, sample size, patient characteristics, country, study design,
number of defect sizes, length of follow-up, evaluation indicators, outcome measures, and inference.
Quality assessment
Two reviewers (AM and GM) independently assessed the methedological qualities of included studies.
The third reviewer was contacted in case of uncertainty about the evaluation. The Cochrane Handbook for
Systematic Reviews of Interventions' Risk of Bias tool was utilized to measure the quality of the
identified RCTs (Version 5.1.0) [7]. Sequence generation, allocation concealment, examiner masking,
inadequate outcome data, lack of selective outcome reporting, and other forms of bias were employed to
assess the selected RCTs.

Table 2: Characteristics of the included studies

 Author, year Study Country Patients and Sites Follow-up Outcome Treatment Control Summary
design intervention (PRP+ABBM) (ABBM)

Dori, 2009 [5] RCT Hungary 30 30 1 year CAL was the PD decreased= PD decreased=
(parallel) primary 8.6 – 1.8 mm to 8.5 – 2.0 mm to No effect.
T: PRP + ABBM outcome 3.4 – 1.4 mm 3.2 – 1.3 mm
(n=15) measure. (P<0.001) (P<0.001)
CAL reduced=
C: ABBM Secondary 9.9 – 1.7 to CAL reduced
outcome: 5.3 – 1.8 9.6 – 1.9
(n=15) plaque index GR: To 4.9 – 1.5 In instances managed with PRP + ABBM, CAL gain
(PI), gingival Changed= 1.3 –
index (GI), 1.1 to 1.9 – 1.8 GR changed
bleeding on 1.1 – 0.9 to 1.7
probing (BOP), – 1.5
probing depth
(PD), gingival At the 1-year
recession (GR) postoperative re-
evaluation, there were
no statistically
significant changes
between the two
compared groups in
any of the evaluated
measures.
Xiang et al., 2006 RCT (split- China 10 17 1 year Clinical PL changed from Positive effect.
[8] mouth parameter: 0.67±0.71 PL changed
design) T: PRP+BPBM PL: plaque to from When compared to
(n=9) index. BI: 0.67±0.50 0.75±0.46 to utilizing BPBM alone,
bleeding index. 0.75±0.71 the therapy combining
C: BPBM (n=8) PD: probing BI changed from BI changed PRP + BPBM
depth. RAL: 0.89±1.05 to from improved periodontal
relative 0.89±0.78 0.88±0.64 to intrabony
 attachment 1.00±0.93 abnormalities in more
level. GR: PD changed from PD changed positive clinical
gingival 8.22±1.31 to from parameter.
recession. BP: 3.44±0.47 7.78±1.16 to
bone probing RAL changed 4.30±0.81
level. from RAL changed
Radiographic 16.67±2.19 to from
parameters: 12.16±1.97 16.33±1.57 to
Change in GR (mm) changed 13.48±1.17
alveolar bone from
mass 0.56±1.47 to REC (mm)
0.80±1.62 changed from
BP changed from 0.43±1.12 to
10.94±1.96 to 0.83±1.07
6.39±1.71
DSR analysis of BP changed
baseline and 1 from
year 11.56±1.45 to
postoperatively 8.69±1.25
revealed that the
test group's
alveolar bone
density increased
radiographically
more than the
control group.
Hanna, 2004 RCT (split U.S 13 26 6 months Positive effect.
[2] mouth) PD, CAL, REC The mean variations ()The
at 6mean variationsClinically,
months the
() at 6 months sites
T: PRP + BDX involved in using PRP
(n=13) as the treatment option
appeared less
PD reduction: 3.54; CAL
PD gain:
reduction:
3.15 mm;
.53 mm;
and CAL
GR: 0.38
gain: 2.31 mm; and GR: 0.23 mm,
C: BDX (n=13) inflamed, less swollen,
and denser in
appearance at the end
 of 1 week when
compared with the
contralateral control
sites

Table 2 demonstrates the clinical and radiographic characteristics of the three studies: Dori, 2009; Xiang et al., 2006; and Hanna, 2004.
ABBM: Anorganic bovine bone material; BDX: Bovine derived xenograft; BPBM: Bovine porous bone mineral; CAL: clinical attachment level;
PI: plaque index; GI: gingival index; BOP: bleeding on probing; PD probing depth; GR: gingival recession; RAL: relative attachment level;
DSR: Digital subtraction radiography
 3. Results

Search results
The process of extracting relevant information and including the final three articles is depicted in the
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram (Fig 1).
The process shows that the initial database search yielded 1001 studies. Removal of duplicate studies
resulted in 748 studies. Thus, title and abstract screening of 748 studies was conducted. Out of these, 59
articles were deemed suitable for full-text eligibility. Finally, 56 studies were eliminated as they failed to
implement the inclusion criteria, and three studies were included for qualitative synthesis in the
systematic review.
 Figure 1: Flowchart summarizing the article selection process (n—number of studies)

Records identified through Additional records identified

database searching (PubMed, through Google Scholar and
fica
tio

Cochrane, Embase & Scopus) other sources

n

(n = 935) (n = 66)

Duplicates
(n = 253)

Records after duplicates removed

(n = 748)
nin
g

Records screened for titles and

abstracts
(n = 748)

Papers rejected at title

and abstract stage. (n =
689)
Elig
ibil
ity

Full-text articles assessed for

eligibility
(n = 59)
Full-text articles excluded,
with reasons
(n = 56)
a. Failed to meet the
eligibility criteria.
b. Absence of 6-month
follow-up.
c. Comparison with saline.
d

Studies included in
qualitative synthesis
(n = 3)
Study characteristics
Dori et al. conducted an RCT parallel study, while the other studies, Xiang et al. 2006; and Hanna, 2004
designed an RCT split-mouth study. The study location has also been reported in Dori et al.'s study in
Hungary, Xiang et al.'s study in China, and Hanna's study in the United States of America.
Overall, the sample size for Dori, 2009; Xiang et al., 2006; and Hanna, 2004 was 30, 10, and 13,
respectively. The number of participants was distributed into the treatment and control groups, where the
treatment group referred to the group treated with a combination of PRP and Xenograft, and the control
group included Xenograft alone—in the study by Dori et al. The treatment group included 15 participants
treated with PRP + inorganic bovine bone material (ABBM), while the control group included 15
participants treated with ABBM alone. The study by Xiang et al. included a total of 17 sites where the
treatment group was treated with PRP and bovine porous bone mineral (BPBM) (n=9); the control group
underwent treatment with BPBM (n=8). Hanna et al. included a total of 26 sites where the treatment
group was treated with PRP and BDX (n=13), while the control group was treated with bovine-derived
Xenograft (BDX) alone (n=13). The studies by Dori et al., and Xiang et al., were followed-up for one
year, while Hanna et al. conducted the study for six months.

Clinical and radiographic outcomes

The three studies assessed the clinical parameters: clinical attachment level (CAL), pocket depth (PD),
plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing depth (PD), gingival
recession (GR). However, radiographic parameters regarding the change in alveolar bone mass were only
investigated in the study by Xiang et al. Clinically, the periodontal parameters showed a statistically
significant difference in the two studies (Xiang et al., 2006 and Hanna et al., 2004), whereas no
significant difference between the treatment and control group was identified by Dori et al. (2009).
According to Xiang et al., baseline DSR analysis revealed an improvement in the radiographic
parameters, and one year after surgery, the test group (PRP and BPBM) demonstrated greater
radiographic gains in alveolar bone mass when compared to the control group (BPBM).
Table 3: Method of platelet-rich plasma preparation in the selected studies

Author, PRP preparation Centrifugation Activator (s) of coagulation Platelet count

year steps

Dori, Curasan PRP kit Two steps in 15 100 U/mL sterile bovine not recorded immediately, After
2009 mins interval 1220 thrombin in a sterile saline treatment: 834.3 103 /L 2519.6
[5] r.p.m., & 3600 solution that contains 10% 103 /L
r.p.m. CaCl2
Xiang, Commercial 15 minutes at 1220 Sterile human thrombin (RAAS 1225－1450)×103 /µl
2006 enzyme-linked rpm Blood Products Co., Ltd.
[8] immunosorbent Shanghai, China) was mixed to
assay (ELISA) kit sterile saline solution
containing 10% calcium
chloride to activate it.
Hanna, SmartPReP Two cycles of 10 1 milliliter of 10% CaCl2 Not recorded
2004 mins and 15 mins combined with 1000 US units
[2] 2400 r.p.m. & of topical thrombin
3600 r.p.m.

RPM: rotation per minute; CaCl2: calcium chloride; ELISA: enzyme-linked immunosorbent assay
The PRP preparation kit varied among the three studies. Dori et al. used the Curasan PRP kit, Xiang et al.
used the Commercial enzyme-linked immunosorbent assay (ELISA) kit, and Hanna et al. used the
SmartPReP kit. Similar centrifugation steps (1220 r/min for 15 minutes) were performed in the study
conducted by Dori et al. and Xiang et al., whereas Hanna et al. performed two centrifugation steps
including 2400 r.p.m., 10 min & 3600 r.p.m., 15 min.
The activator in all three studies was a sterile saline solution containing 10 % CaCl2 mixed with 100
U/mL sterile bovine thrombin. Dori et al., and Hanna et al., did not record the platelet count directly,
while the platelet count was recorded as 1225－1450)×103 /µl by Xiang et al.
Table 4 demonstrate the risk of bias for the included papers according to the Cochrane Handbook
guidelines
The included studies (Dori et al., Xiang et al., and Hanna et al.) measured low risk of bias and consisted
of a high-quality, randomized, controlled trial. In all three trials, there was a relatively small sample size
and an unexplained placebo, indicating bias.
Table 4: The risk of bias
Included Random Allocation Blinding of Blinding of Incomplete Selective Other Overall
studies sequence concealment participants and outcome outcome data reporting bias Bias
generation personnel assessment (Attrition (reporting
(selection (Performance (Detection bias) bias)
bias) bias) bias)

Dori et al. Low Low Low Low Low High (No N/A Low
placebo, less
sample size)
Xiang-Ying Low Low Low Low Low High (Less N/A Low
et al., sample size
and no
placebo
group)
Hanna et Low Low Low Low Low High (No N/A Low
al., placebo, less
sample size)
Discussion

The current systematic review aimed to evaluate the efficacy of Xenograft in conjunction with PRP or
alone in treating intra-bony defects based on randomized control trials, resulting in substantial
improvement in CAL gain and PD reduction compared to controls. Methodological quality assessment of
the included studies was per the CONSORT statement and measured a lower risk of bias. The limited
sample size of included studies made it difficult to perform a meta-analysis, which will not produce a
significant power analysis. Previous research has shown a reduction in pocket depth and CAL gain by 60-
65% with the utilization of bone graft and PRP. () Although the positive gain is measured with treatment,
some residual effect remains. This is one of the main reasons that probed researchers to add bioactive
material and bone grafts to PRP in treating intra-bony defects. This eventually helps to resolve intra-bony
defects and maintain the healthy periodontal status of the patient. () In the 2009 study by Dori et al., PRP
with an organic bovine bone material (ABBM) and ABBM alone showed a significant reduction in PD
and gained in CAL in both categories after one year of regenerative surgery; however, no statistically
significant differences were observed when compared to each other in terms of the investigated
parameters at the end of the 1-year follow-up. The observation of a significant clinical gain when PRP
and ABBM are utilized is consistent with previous research. Observing a significant clinical gain when
PRP and ABBM are utilized is consistent with previous research. One of the controlled clinical studies
using a similar study design as the present trial showed significant improvement in the parameter
compared to the baseline at 6-month follow-up. [2] Nevertheless, the group with PRP had significantly
improved outcomes regarding CAL gain and PD reduction compared to the group with graft alone. In the
study mentioned above, the mean CAL gain was 3.15mm in the group of PRP and ABBM when
compared to the group of ABBM alone with a 2.31mm gain. CAL gain obtained with PRP showed 77%
against the group with graft alone (38.8%).[2]

Xiang et al. (2006) executed a study to assess the clinical and radiological characteristics [8]. Digital
subtraction radiography was used to examine each defect-standardized periapical radiograph collected at
the baseline, two weeks, and one year following the surgery (DSR). However, the use of PRP and the
BPBM significantly improved the outcome clinically and radiographically postoperatively after one year.
[8] Results from both treatment modalities, particularly regarding PRP with bovine porous bone mineral
(BPBM) and BPBM alone, showed improvement compared to the baseline. Compared to the control
group, PRP and BPBM groups demonstrated 1.67mm more CAL gain (p=0.01), respectively.[8] When
compared to other traditional radiography, DSR demonstrates excellent bone change detection.
Additionally, since the BPBM utilized was radiopaque, using DSR aids in removing the BPBM impact
and gives better evidence for the efficiency of PRP. To date, DSR has not been employed to evaluate the
PRP effect in the intrabony defect. The reentry procedure is the most accurate clinical method used to
measure the intrabony defect directly. Nevertheless, it may harm the new regenerative tissue and cause
discomfort to the patient. Another reliable and less uncomfortable option for the patient is bone probing
under local anesthesia without re-entering into the site, and no significant difference is observed from the
reentry measurement. [9]

Hanna et al. demonstrated the efficacy of Xenograft in combination with PRP and, alone clinically,
reported a positive outcome with the combination as compared to Xenograft alone in treating intra-bony
defects [2]. Levovic et al. (2002) evaluated the efficacy of PRP with Xenograft (BDX) material with or
without the utilization of biomaterial and demonstrated that CAL gain was 3.8mm and PD reduction was
3.9mm compared to controls [9] This difference could be attributed to the stick consistency of PRP during
preparation which not only aids coagulation but also adheres to the root surface, helping in the
regeneration of connective tissue.

The current systematic review demonstrates that studies using a parallel design and those using a split-
mouth technique differ significantly. This result also implies that different study designs are not equally
efficient in clinically analyzing Xenograft efficacy. The systematic review showed no discernible
difference between the two trial designs using PRP as an adjuvant. The split-mouth and parallel designs in
binary and continuous data showed no statistically significant differences, according to similar findings
from another recent systematic review. Hou et al. (2016) [11] contrasted this by arguing that "varied
research patterns are not equally effective in assessing the PRP efficacy." The Cochrane Oral Health
Group advises that split-mouth and parallel techniques be evaluated separately in subgroup analysis. The
split-mouth design's main benefit is its significantly lower intrasubject variability, which is necessary
when measuring certain factors, including postoperative problems, soft- and hard-tissue healing, and
esthetics. Comparing the control and experimental groups statistically for the outcome variables of PD
reduction and CAL gain using a parallel design, as opposed to a split-mouth design, is simpler and more
appropriate because it is unaffected by patient circumstances. [12]

The three included studies follow different study designs; Hanna et al. (2004) [2] and Xing et al. [8] used
split-mouth, while Dori et al. [5] utilized the parallel mouth technique. Moreover, the evaluation periods
were also different in all three studies varying from 3 to 6 months and a year. However, the results of all
three studies demonstrated an increase in CAL gain and reduction in PD in patients treated with
xenografts in combination with PRP compared to controls. Evidence from previous studies suggests that
the mechanism of PRP on the regeneration of periodontal tissue is still unknown. Studies on xenograft
material reported increasing alveolar bone, periodontal ligament, and the cementum in patients with
chronic periodontitis. Hence, treatment with Xenograft alone for intra-bony defects may improve CAL
and PD clinically.

While evaluating results clinically and radiographically with the combination of PRP and Xenograft, it is
evident that there is a significant difference noted in CAL gain and PD reduction. This could be due to the
property of PRP, which aids in synthesizing growth factors and degranulation of α granules. The PRP also
contains three proteins: fibronectin, fibrinogen, and vitronectin. These proteins act as a matrix for
connective tissue and cell adhesive for osteoconductive. Additionally, PRP acts as a hemostatic agent due
to its sticky characteristic, which helps in blood coagulation and adherence of graft material. [11] Overall,
PRP, in conjunction with any bioactive material, reduces the operating time and is helpful to clinicians
and patients. No conflicts in the findings of included studies have been noted as the designed RCT has
examined the combination of PRP with Xenograft.

Due to the dearth of available data, the current systematic review hypothesis should be again evaluated by
additional RCTs on the use of Xenograft and PRP. Another important speculation would be the
evaluation of RCTs that have acquired PRP in conjunction with different materials simultaneously. This
will eventually help clinicians in quantifying the beneficial properties of PRP. Another valid reason for
differences in the results of studies might be a heterogenous sample with limited sample sizes. Gunsolley
et al. (1998) [12] suggested that sample size must be calculated according to the appropriate assumption
and sufficient statistical power to provide quality evidence. The three studies demonstrated that the
therapeutic use of PRP is safe and postoperative complications are less. Unfortunately, none of the
included RCTs provided information on whether adjunctive use of PRP improves aesthetics, a significant
improvement in hard and soft tissue healing, and clinical handling management of PRP in combination
with Xenograft.

The main strength of the current systematic review was the selection of included studies, as authors
utilized a range of databases (including manual search) and strict inclusion criteria. First, this review has
various limitations, including studies that have not estimated the proper sample size selection criteria.
This eventually limits the autologous efficacy of PRP in conjunction with Xenograft. Heterogeneity was
present among different studies about surgical technique, experimental designs, PRP preparation method,
and follow-up duration. More research is required in this field to consider specific factors, such as
blinding methods, allocation concealment, and sample size calculation. Even though the findings of
included studies suggest a positive effect of PRP and Xenograft, long terms follow-up clinical trails with
larger sample sizes should be planned to evaluate the beneficial effect of PRP in conjunction with
Xenograft. Future studies should focus more on evaluating additional benefits of PRP, such as aesthetics,
wound healing property, and a subjective index as a secondary outcome variable. This will eventually
provide researchers with in-depth knowledge of the efficacy of PRP with Xenograft.

Conclusions
Within the limitations of this comprehensive review, it may be suggested that PRP, in conjunction with
Xenograft, can have a beneficial effect in the treatment of intrabody osseous defects. PD reduction and
CAL gain were observed in two of the three investigated studies. Due to the short follow-up and
substantial heterogeneity of the included studies, caution should be advised while applying the results in
clinical settings.

References
1. Khairat, R., Jan, S.M., & Beh, R. (2019). Treatment of intrabony bone defect with xenograft
material: A case report. Int J Appl Dent Sci, 5(2), 473-475.
https://www.oraljournal.com/pdf/2019/vol5issue2/PartH/5-2-83-361.pdf
2. Hanna, R., Trejo, P. M., & Weltman, R. L. (2004). Treatment of intrabony defects with bovine-
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