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INTRODUCTION
Osteoradionecrosis (ORN) is one of the redundant complications of radiotherapy
characterized by necrosis of irradiated bone. It develops due to progressive hypoxia, hypo-
vascularization, and hypo-cellularity of the affected bone. Radiation causes inflammation of
small blood vessels (endarteritis) resulting in the development of thrombi and occlusion of
the vascular lumen. It also causes altered collagen synthesis. Compromised tissue perfusion
and impaired repair and remodeling capacity make the bone vulnerable to necrosis, even
with mild provocation.[1] The mandible is the most commonly affected site following head
and neck radiation therapy. Trauma, dental extraction or other surgical manipulations, poor
oral hygiene, irritation from ill-fitting denture, usage of tobacco and alcohol are considered
to be the precipitating factors.
Clinically, ORN may manifest as mild discomfort when the lesion is small and localized, as
the lesion progresses, patient may experience pain, swelling, trismus, sequestrum
formation, and pathological fracture. Various treatment modalities are available and are
practiced according to the individuality of the lesion. Small and asymptomatic lesions are
managed conservatively while reserving more invasive surgical management for
progressive and symptomatic lesions.[2] The aim of this article is to present two cases of
ORN of mandible that developed following irradiation for squamous cell carcinoma for
which adult stem cell therapy alone with surgery was tried following failure of
conventional treatment methods. The first case was treated by autologous bone marrow
concentrate, and the second case was treated with allogeneic dental pulp stem cells (DPSC).
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CASE REPORTS
Case 1
A 48-year-old male reported to our Dental Clinic in March 2010 with the complaint of
severe pain and unhealed extraction socket. Past medical history revealed that he had
undergone radiotherapy for the management of carcinoma of the soft palate 3 years back. A
year after radiotherapy, the tooth on the lower right side was extracted, and the socket had
not healed for more than 6 months.
Clinical examination revealed unhealed socket in lower right second molar area with
exposure of underlying bone. The extracted socket had apparently developed ORN. The
patient was treated by us for nearly 1 year through conventional methods such as wound
debridement, warm saline irrigation, socket dressing with zinc oxide eugenol, and antibiotic
dressing. Since the complications recurred between periods of conservative treatment and
there was no sign of clinical improvement, it was decided to treat the case using stem cell
therapy. Detailed and specific informed consent was obtained from the patient and
institutional ethical committee approval obtained. Panoramic radiograph taken before
current therapy showed an area of bone destruction in right 2nd molar region with irregular
margins. Both radiolucency and radio-opacities were observed within the lesion suggestive
of chronic osteomyelitis. There was a suspicion of a hairline pathologic fracture (arrow) in
the radiograph [Figure 1].
Figure 1
Figure 2
Clinical outcome
The patient responded well with a gradual reduction in pain, and there was no discharge
from intraoral lesion after 2 months. The radiograph showed signs of early bone formation
at 2nd month [Figure 3] and evidence of consolidated bone formation after 6 months with
resolution of suspected fracture line [Figure 4]. The patient remained asymptomatic and
complete bone remodeling was noticed after 1 year. The patient was followed for more than
2 years and was symptom-free. There were no untoward effects noted related to this
treatment.
Figure 3
Figure 4
Case 2
A 47-year-old male reported to our department with the complaints of pus discharge on the
left side cheek for 1 year [Figure 5].
Figure 5
Extraoral sinus
The history revealed post-surgical radiotherapy and chemotherapy for squamous cell
carcinoma in left tonsillar region. Clinical examination showed nonhealing wound in the
36, 37 region and multiple grossly decayed teeth in the left mandibular quadrant with pus
discharge communicating extraorally through a sinus. Orthopantomogram revealed mixed
radiolucency and multiple dental caries in left side body of the mandible [Figure 6].
Eventually, the condition was diagnosed as ORN of mandible.
Figure 6
Preoperative OPG
Initially, the patient was treated with a broad spectrum antibiotics and clindamycin. Patient
was also prescribed pentoxyphylline (trentol) 500 mg and Vitamin E (evion) twice daily for
6 weeks to improve circulation. It was then decided to complete the treatment with stem
cell therapy.
Figure 7
Figure 8
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DISCUSSION
Mesenchymal stem cells derived from dental pulp differentiate into osteoblasts capable of
producing bone. Evidences exist showing that mesenchymal stem cells can be seeded on
scaffolds and used to repair human mandibular defects.[4,5,6] According to Ito et al.[7] a
gel made with DPSC and PRP showed excellent osteogenic characteristics and significant
new bone formation. The DPSC used in this case were cultured in a GMP lab and obtained
from the 2nd passage.
The therapeutic application of bone marrow-derived cells for human bone lesions is not
new. Adult stem cells have been the subject of many in vitro and animal experiments,
demonstrating significant potential in the management of bone lesions. Stimulation with
granulocyte colony-stimulating factor, blood aphaeresis, and expanded bone marrow in
autologous and homologous procedures have been attempted.[8] There is substantial
evidence that human bone marrow supplies the patient with not only hematopoietic cells
but also a significant number of mesenchymal stem cells.[9] Bone Marrow harvested stem
cells and progenitor cells (BMSC) may be capable of solid organ repair and it has been
demonstrated that adult human mesenchymal stem cells from bone marrow can represent a
promising source of skeletal regeneration.[10]
The authors use of bone marrow aspirate concentrate (BMAC) for the treatment of ORN of
mandible is first of its kind and the authors are not aware of any earlier reports published on
the above said procedure for ORN of mandible. There are significant data supporting the
clinical efficacy of BMAC stem cells. An immediate autologous transplantation of BMAC
can prevent complications of transplanted cells such as pre-aging (telomere shortening),
reduced viability, or dedifferentiation/reprogramming that is associated with in-
vitro cultivation.[11]
Recently, images of neo-angiogenesis following stem cell therapy in ORN of mandible
have been demonstrated by gadolinium-enhanced magnetic resonance scan. Vascular
growth is the basis for regeneration in all tissues, delivering oxygen, nutrients, chemical
signaling, migrating cells, and immunity. Good blood supply with sufficient viable cells are
required for osteogenesis.[8]
Earlier Ficoll-hypaque centrifugation procedures were used for isolation and cellular
expansion in-vitro.[10] The cellular composition of concentrate prepared by BMAC system
differs from Ficoll method with respect to the number of colony forming unit cells
(mesenchymal cells).[11]
The volume reduction protocol of the closed centrifuge allows for the highest concentrate
of the mesenchymal stem cells and therefore is a promising candidate for instant stem cell
therapy.[12] Sauerbier et al. have shown hard tissue regeneration in vitro by using both
Ficoll method and BMAC method.[11] Another major concern in stem cell therapy is
safety. To our knowledge, there have been no reports of adverse reactions or complications.
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CONCLUSION
Authors have successfully treated two cases of ORN with BMAC and DPSC and PRP,
respectively. More experience is required to arrive at a definitive conclusion regarding the
benefits of the stem cell therapy for mandibular ORN of the bone due to various etiological
factors.
Stem cell-based reconstruction may be attempted in unresponsive ORN cases before other
major deformative procedures are planned.
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Footnotes
Source of Support: Nil
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REFERENCES
1. Silvestre-Rangil J, Silvestre FJ. Clinico-therapeutic management of osteoradionecrosis: A
literature review and update. Med Oral Patol Oral Cir Bucal. 2011;16:e900–4. [PubMed]
3. Turan RG, Bozdag-Turan I, Ortak J, Akin I, Kische S, Schneider H, et al. Improvement of cardiac
function by intracoronary freshly isolated bone marrow cells transplantation in patients with acute
myocardial infarction. Circ J. 2011;75:683–91. [PubMed]
4. Giuliani A, Manescu A, Langer M, Rustichelli F, Desiderio V, Paino F, et al. Three years after
transplants in human mandibles, histological and in-line holotomography revealed that stem cells
regenerated a compact rather than a spongy bone: Biological and clinical implications. Stem Cells
Transl Med. 2013;2:316–24.[PMC free article] [PubMed]
5. Wolff J, Sándor GK, Miettinen A, Tuovinen VJ, Mannerström B, Patrikoski M, et al. GMP-level
adipose stem cells combined with computer-aided manufacturing to reconstruct mandibular
ameloblastoma resection defects: Experience with three cases. Ann Maxillofac Surg. 2013;3:114–
25. [PMC free article] [PubMed]
6. Sándor GK, Numminen J, Wolff J, Thesleff T, Miettinen A, Tuovinen VJ, et al. Adipose stem cells
used to reconstruct 13 cases with cranio-maxillofacial hard-tissue defects. Stem Cells Transl
Med. 2014;3:530–40.[PMC free article] [PubMed]
7. Ito K, Yamada Y, Nakamura S, Ueda M. Osteogenic potential of effective bone engineering using
dental pulp stem cells, bone marrow stem cells, and periosteal cells for osseointegration of dental
implants. Int J Oral Maxillofac Implants. 2011;26:947–54. [PubMed]
8. Mendonça JJ, Juiz-Lopez P. Regenerative facial reconstruction of terminal stage
osteoradionecrosis and other advanced craniofacial diseases with adult cultured stem and
progenitor cells. Plast Reconstr Surg.2010;126:1699–709. [PubMed]
9. Smiler D, Soltan M, Albitar M. Toward the identification of mesenchymal stem cells in bone
marrow and peripheral blood for bone regeneration. Implant Dent. 2008;17:236–47. [PubMed]
10. Cella L, Oppici A, Arbasi M, Moretto M, Piepoli M, Vallisa D, et al. Autologous bone marrow
stem cell intralesional transplantation repairing bisphosphonate related osteonecrosis of the
jaw. Head Face Med.2011;7:16. [PMC free article] [PubMed]
11. Sauerbier S, Stricker A, Kuschnierz J, Bühler F, Oshima T, Xavier SP, et al. In vivo comparison of
hard tissue regeneration with human mesenchymal stem cells processed with either the FICOLL
method or the BMAC method. Tissue Eng Part C Methods. 2010;16:215–23. [PubMed]
12. Kasten P, Beyen I, Egermann M, Suda AJ, Moghaddam AA, Zimmermann G, et al. Instant stem
cell therapy: Characterization and concentration of human mesenchymal stem cells in vitro. Eur
Cell Mater.2008;16:47–55. [PubMed]
Regeneration of mandibular osteoradionecrosis defect
with platelet rich plasma gel.
1. M. SCALA1,
2. M. GIPPONI2,
3. P. MEREU1,
4. P. STRADA3,
5. R. CORVÒ4,
6. A. MURAGLIA5,
7. M. MASSA6,
8. S. BERTOGLIO1,5,
9. P. SANTI7 and
10. F. CAFIERO1
+ Author Affiliations
1. 1Department of Surgical Oncology, National Institute for Cancer Research
IST, Genoa, Italy
2. 2General Surgery, Colo-Rectal Unit, St. Martino Hospital, Genoa, Italy
3. 3Blood Transfusion Centre, St. Martino Hospital, Genoa, Italy
4. 4Therapeutic Oncology Centre, Genoa, Italy
5. 5Biorigen SRL., Genoa, Italy
6. 6Plastic Surgery Unit, National Institute for Cancer Research IST, Genoa, Italy
7. 7Plastic Surgery Unit, University of Genoa, School of Medicine, Genoa, Italy
1. Correspondence to: Marco Gipponi, MD, A.O.U. “San Martino” Genova, L.go Rossana
Benzi 10, Genova 16132, Italy. e-mail: marco.gipponi@unige.it
Next Section
Abstract
Osteoradionecrosis
mandible
regeneration
Radiation therapy is a treatment modality used in a wide variety of maxillofacial cancer, either
as a primary approach or in conjunction with chemotherapy and surgery. Despite this modality
of cancer treatment, it causes changes in the skeletal system by decreased bone vascularity
and repair capacity, nonetheless it is still preferred as the treatment of choice for the sake of
eliminating the malignant neoplasm.
In this case report, we investigated the effect of autologous PRP for regeneration of the
mandibular necrotic defects in a cancer patients who previously underwent radiation therapy.
We speculated that the concentrated mitogenic and vascular enhancing GF within the PRP
would improve bone regeneration in the necrotic defects by recruiting vessels and enhancing
cell migration from the healthy surrounding bone tissue.
Case Report
A white Caucasian male age of 44 was diagnosed for oral squamous cell carcinoma (SCC) of
the left half of the tongue. The procedures of diagnosis, surgical intervention and follow up
were carried out in the Institute of Cancer Research IST-Genova and were approved by the
Institutional Ethics Committee.
A partial left glossectomy was performed with conservative neck dissection (CND) and
bilateral suprahyoid lymph node dissection. Pathological staging of the tumor was PT1pN0.
Following surgery, the patient received adjuvant radiotherapy (RT). The schedule consisted
of 33 visits, 5 visits per week; each consisted of a dose of 200 cGy with a total dose of 6600
cGy. Lonidamine - an indazole carboxylic acid that has been shown to be synergistic with
radiotherapy- was added to the radiotherapeutic protocol (23). After four years, the patient
showed up edentulous, with stomatitis, purulent abscesses and exposed alveolar processes
of the right mandible. He reported xerostomia and teeth exfoliation during the previous
years. The panoramic X-ray showed diffuse alveolar resorption together with mandibular
radiolusencies thus a diagnosis for ORN was subsequently made (Figure 1A). Pus bacterial
culture evidenced the presence of Prevotella melaninogenica and Prevotella
buccae (isolated from anaerobic culture) andStreptococcus anginosus. The patient was
treated with Moxifloxacin Hydrochloride 600 mg daily dose for 20 days, subjected to regular
oral antisepsis and eventually scheduled for regenerative surgery with autologous PRP.
During surgery, the necrotic bone was removed and the PRP gel was introduced into the
defect area. A panoramic X-ray was performed two years later (Figure 1B).
Platelets rich plasma gel preparation. Patients were hosted at the Immunohematology
Centre – St. Martino Hospital, Genoa, Italy two days before surgery. A quantity of 450 ml of
whole blood was collected and immediately centrifuged at 200g for 30 minutes to separate
packed red blood cells and PRP. The red blood cells were reinfused to the patient while the
PRP was re-centrifuged at 2000g for 5 minutes to precipitate the platelets and separate the
platelets poor plasma (PPP) from the platelets concentrate (PC). PPP was immediately
frozen at −80°C in a mechanical refrigerator then at 4°C for 18 hours for spontaneous
thawing while the PC was preserved at 22°C in continuous agitation.
With regards to the quality control of the product, PC had a platelet count equal to 60×10 9,
residual leucocytes equal to 0.2×109, and maximum volume of 30 ml. The cryoprecipitate
had factor VIII equal to 70 μl/100 ml, fibrinogen equal to 140 mg/unit and maximum volume
of 30 ml. Autologous thrombin was prepared from 27 ml of blood collected into three sterile
tubes containing 1ml of acid-citrate-dextrose (ACD) anticoagulant solution. Tubes were
centrifuged at 900g for 10 minutes and then plasma was transferred into a second sterile
tube. One ml of sterile calcium chloride was added to each 5ml of plasma. The tubes were
incubated for 30 minutes at 37°C. The plasma clot was then re-centrifuged for 10 minutes
at 900g. The supernatant thrombin was stored at −30°C until the time of use.
At the time of surgery, equal volumes of PC and cryoprecipitate were mixed in a sterile
Petri's dish and 1ml of thrombin and 1 ml of calcium gluconate were added to each 10 ml of
the PC-cryoprecipitate mixture. The gel resulted ready for application after 10-15 minutes of
adding thrombin and calcium ions.
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Figure 1.
The regenerative treatment with PRP did not show any complications; the patient was
discharged the day after the surgical procedure. There was no evidence of postoperative
infection or any oro-mandibular fistulae. The mandibular bone repaired completely after
being covered by mucosa with evidence of surgical wound healing within 8 postoperative
days.
After the reconstructive surgery, the 2-year follow up panoramic radiograph showed
complete regain of the alveolar bone mass and mandibular bone regeneration in the place
of the large irregular radiolucency (Figure 1 A and B).
Previous SectionNext Section
Discussion
In this case report, a successful regeneration of the mandibular integrity was obtained by
introducing the platelets GF into the necrotic defect mimicking the natural healing process
otherwise compromised by inadequate vascularization. To our knowledge, this is the first
study that reports beneficial effects of PRP on ORN defect healing with a two-year follow up
period. In this case, we did not test if the ORN was resistant to HBO (Marx stage III disease)
thus we cannot assume that PRP is effective in such case. We should eventually remark that
the patient had edentulous mandible after the regenerative procedure, which might have
also reduced complications that usually occur in the presence of periodontal pathologies or
septic foci.
In conclusion, we believe that the use of PRP associated to conservative strategies for ORN
treatment may reduce or eliminate the need for invasive procedures such as the resection
and reconstruction of the mandible with vascular flaps.
References
1. ↵
1. Mitchell MJ,
2. Logan PM
: Radiation-induced changes in bone. Radiographics18: 1125-1136, 1998.
MedlineGoogle Scholar
2. ↵
1. Gal TJ,
2. Yueh B,
3. Futran ND
: Influence of prior hyperbaric oxygen therapy in complications following
microvascular reconstruction for advanced osteoradionecrosis. Arch Otolaryngol Head
Neck Surg 129(1): 72-76, 2003.
CrossRefMedlineGoogle Scholar
3. ↵
1. Bonan PR,
2. Lopes MA,
3. Pires FR,
4. Almeida OP
: Dental management of low socioeconomic level patients before radiotherapy of the
head and neck with special emphasis on the prevention of osteoradionecrosis. Braz
Dent J 17(4):336-342, 2006.
MedlineGoogle Scholar
4. ↵
1. Melo MD,
2. Obeid G
: Osteonecrosis of the jaws in patients with a history of receiving bisphosphonate
therapy: strategies for prevention and early recognition. J Am Dent
Assoc 136(12): 1675-1681, 2005.
Abstract/FREE Full Text
5. ↵
1. Cetinkaya BO,
2. Keles GC,
3. Ayas B,
4. Sakallioglu EE,
5. Acikgoz G
: The expression of vascular endothelial growth factor in a rat model at destruction
and healing stages of periodontal disease. J Periodontol 78(6): 1129-1135, 2007.
MedlineGoogle Scholar
6.
1. Rai B,
2. Oest ME,
3. Dupont KM,
4. Ho KH,
5. Teoh SH,
6. Guldberg RE
: Combination of platelet-rich plasma with polycaprolactone-tricalcium phosphate
scaffolds for segmental bone defect repair. J Biomed Mater Res 81(4): 888-899,2007.
Google Scholar
7.
1. Del Papa N,
2. Quirici N,
3. Soligo D,
4. et al.
: Bone marrow endothelial progenitors are defective in systemic sclerosis. Arthritis
Rheum 54(8): 2605-2615, 2006.
CrossRefMedlineGoogle Scholar
8. ↵
1. Lienau J,
2. Schell H,
3. Duda GN,
4. Seebeck P,
5. Muchow S,
6. Bail HJ
: Initial vascularization and tissue differentiation are influenced by fixation stability. J
Orthop Res23(3): 639-645, 2005.
CrossRefMedlineGoogle Scholar
9. ↵
1. Marx RE
: Osteoradionecrosis: a new concept of its pathophysiology. J Oral Maxillofac
Surg 41(5): 283-8, 1983.
CrossRefMedlineGoogle Scholar
10. ↵
1. Curi MM,
2. Oliveira dos Santos M,
3. Feher O,
4. Faria JC,
5. Rodrigues ML,
6. Kowalski LP
:Management of extensive osteoradionecrosis of the mandible with radical resection
and immediate microvascular reconstruction. J Oral Maxillofac Surg65(3): 434-
438, 2007.
CrossRefMedlineGoogle Scholar
11.
1. Hao S CC,
2. Wei F,
3. Chen C,
4. Yeh AR,
5. Su J
: Systematic management of Osteoradionecrosis in the head and
neck. Laryngoscope 109: 1324-1328,1999.
CrossRefMedlineGoogle Scholar
12.
1. Shaha AR CP,
2. Cordeiro PG,
3. Hidalgo DA,
4. et al.
: Resection and immediate microvascular reconstruction in the management of
osteoradionecrosis of the mandible. Head Neck 19: 406-411, 1997.
MedlineGoogle Scholar
13. ↵
1. Chang DW OH-K,
2. Robb GL,
3. Miller MJ
: Management of advanced mandibular Osteoradionecrosis with free flap
reconstruction. Head Neck 23: 830-835,2001.
CrossRefMedlineGoogle Scholar
14. ↵
1. Balogh JM,
2. Sutherland SE
: Osteoradionecrosis of the mandible: a review. J Otolaryngol 18(5): 245-50, 1989.
MedlineGoogle Scholar
15. ↵
1. Mannai C
: Early implant loading in severely resorbed maxilla using xenograft, autograft, and
platelet-rich plasma in 97 patients. J Oral Maxillofac Surg 64(9): 1420-1426, 2006.
CrossRefMedlineGoogle Scholar
16.
1. Rutkowski JL,
2. Fennell JW,
3. Kern JC,
4. Madison DE,
5. Johnson DA
: Inhibition of alveolar osteitis in mandibular tooth extraction sites using platelet-rich
plasma. J Oral Implantol 33(3): 116-121, 2007.
MedlineGoogle Scholar
17.
1. Boyapati L,
2. Wang HL
: The role of platelet-rich plasma in sinus augmentation: a critical review. Implant
Dent 15(2): 160-170, 2006.
MedlineGoogle Scholar
18.
1. Roukis TS,
2. Zgonis T,
3. Tiernan B
: Autologous platelet-rich plasma for wound and osseous healing: a review of the
literature and commercially available products. Adv Ther 23(2): 218-237, 2006.
MedlineGoogle Scholar
19.
1. Tözüm TF,
2. Demiralp B
: Platelet-rich plasma: a promising innovation in dentistry. J Can Dent
Assoc 69(10): 664-673, 2003.
MedlineGoogle Scholar
20. ↵
1. Scala M,
2. Gipponi M,
3. Pasetti S,
4. et al.
: Clinical applications of autologous cryoplatelet gel for the reconstruction of the
maxillary sinus. A new approach for the treatment of chronic oro-sinusal fistula. In
Vivo 21(3):541-547, 2007.
Abstract/FREE Full Text
21. ↵
1. Kassolis JD,
2. Rosen PS,
3. Reynolds MA
: Alveolar ridge and sinus augmentation utilizing platelet-rich plasma in combination
with freeze-dried bone allograft: case series. J Periodontol 71(10): 1654-1661, 2000.
CrossRefMedlineGoogle Scholar
22. ↵
1. Van den Dolder J,
2. Mooren R,
3. Vloon AP,
4. Stoelinga PJ,
5. Jansen JA
: Platelet-rich plasma: quantification of growth factor levels and the effect on growth
and differentiation of rat bone marrow cells. Tissue Eng 12(11): 3067-3073,2006.
CrossRefMedlineGoogle Scholar
23. ↵
1. Stewart DJ,
2. Eapen L,
3. Girard A,
4. Verma S,
5. Genest P,
6. Evans WK
: Phase II study of lonidamine plus radiotherapy in the treatment of brain
metastases. J Neurooncol 15(1): 19-22, 1993.
MedlineGoogle Scholar
24. ↵
1. D'Souza J,
2. Goru J,
3. Goru S,
4. Brown J,
5. Vaughan ED,
6. Rogers SN
: The influence of hyperbaric oxygen on the outcome of patients treated for
osteoradionecrosis: 8 year study. Int J Oral Maxillofac Surg 36(9): 783-787,2007.
MedlineGoogle Scholar
25.
1. Schoen PJ,
2. Raghoebar GM,
3. Bouma J,
4. et al.
: Rehabilitation of oral function in head and neck cancer patients after radiotherapy
with implant-retained dentures: effects of hyperbaric oxygen therapy. Oral
Oncol 43(4): 379-388, 2007.
CrossRefMedlineGoogle Scholar
26. ↵
1. Maier A,
2. Gaggl A,
3. Klemen H,
4. et al.
: Review of severe osteoradionecrosis treated by surgery alone or surgery with
postoperative hyperbaric oxygenation. Br J Oral Maxillofac Surg 38(3): 173-
176, 2000.
CrossRefMedlineGoogle Scholar
27. ↵
1. Siebrecht MA,
2. De Rooij PP,
3. Arm DM,
4. Olsson ML,
5. Aspenberg P
: Platelet concentrate increases bone ingrowth into porous
hydroxyapatite.Orthopedics 25(2): 169-172, 2002.
MedlineGoogle Scholar
28.
1. Kanno T,
2. Takahashi T,
3. Tsujisawa T,
4. Ariyoshi W,
5. Nishihara T
: Platelet-rich plasma enhances human osteoblast-like cell proliferation and
differentiation. J Oral Maxillofac Surg 63(3): 362-369, 2005.
CrossRefMedlineGoogle Scholar
29.
1. Intini G,
2. Andreana S,
3. Intini FE,
4. Buhite RJ,
5. Bobek LA
: Calcium sulfate and platelet-rich plasma make a novel osteoinductive biomaterial
for bone regeneration. J Transl Med 5: 13, 2007.
CrossRefMedlineGoogle Scholar
30.
1. Ito K,
2. Yamada Y,
3. Naiki T,
4. Ueda M
: Simultaneous implant placement and bone regeneration around dental implants
using tissue-engineered bone with fibrin glue, mesenchymal stem cells and platelet-
rich plasma. Clin Oral Implants Res 17(5): 579-586, 2006.
MedlineGoogle Scholar
31. ↵
1. Hokugo A,
2. Sawada Y,
3. Hokugo R,
4. et al.
: Controlled release of platelet growth factors enhances bone regeneration at rabbit
calvaria. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 104(1): 44-48, 2007.
CrossRefMedlineGoogle Scholar
32. ↵
1. Schwartz HC,
2. Kagan AR
: Osteoradionecrosis of the mandible: scientific basis for clinical staging. Am J Clin
Oncol 25(2): 168-177, 2002.
CrossRefMedlineGoogle Scholar
33. ↵
1. Grageda E
: Platelet-rich plasma and bone graft materials: a review and a standardized research
protocol. Implant Dent 13(4): 301-309, 2004.
MedlineGoogle Scholar
34.
1. Eppley BL,
2. Woodell JE,
3. Higgins J
: Platelet quantification and growth factor analysis from platelet-rich plasma:
implications for wound healing. Plast Reconstr Surg 114(6): 1502-1508, 2004.
MedlineGoogle Scholar
35.
1. Sanchez AR,
2. Sheridan PJ,
3. Kupp LI
: Is platelet-rich plasma the perfect enhancement factor? A current review. Int J Oral
Maxillofac Implants 18(1):93-103, 2003.
MedlineGoogle Scholar
36.
1. Slater M,
2. Patava J,
3. Kingham K,
4. Mason RS
: Involvement of platelets in stimulating osteogenic activity. J Orthop Res 13(5): 655-
663, 1995.
CrossRefMedlineGoogle Scholar
37.
1. Tsukamoto T,
2. Matsui T,
3. Fukase M,
4. Fujita T
: Platelet-derived growth factor B chain homodimer enhances chemotaxis and DNA
synthesis in normal osteoblast-like cells (MC3T3-E1). Biochem Biophys Res
Commun 175(3): 745-751,1991.
CrossRefMedlineGoogle Scholar
38. ↵
1. Kilian O,
2. Flesch I,
3. Wenisch S,
4. et al.
: Effects of platelet growth factors on human mesenchymal stem cells and human
endothelial cells in vitro. Eur J Med Res 9(7): 337-344, 2004.
MedlineGoogle Scholar
39. ↵
1. Kassolis JD,
2. Rosen PS,
3. Reynolds MA
: Alveolar ridge and sinus augmentation utilizing platelet-rich plasma in combination
with freeze-dried bone allograft: case series. J Periodontol 71(10): 1654-1661, 2000.
CrossRefMedlineGoogle Scholar