Platelet concentrates for
surgical use are innovative tools of regenerative medicine, and were widely
tested in oral and maxillofacial surgery. Unfortunately, the literature on the
topic is contradictory and the published data are difficult to sort and
interpret. In periodontology and dentoalveolar surgery, the literature is
particularly dense about the use of the various forms of Platelet-Rich Plasma
(PRP) – Pure Platelet-Rich Plasma (P-PRP) or Leukocyte- and Platelet-Rich Plasma
(L-PRP) – but still limited about Platelet-Rich Fibrin (PRF) subfamilies. In
this first article, we describe and discuss the current published knowledge
about the use of PRP and PRF during tooth avulsion or extraction, mucogingival
surgery, Guided Tissue Regeneration (GTR) or bone filling of periodontal
intrabony defects, and regeneration of alveolar ridges using Guided Bone
Regeneration (GBR), in a comprehensive way and in order to avoid the traps of a
confusing literature and to highlight the underlying universal mechanisms of
these products. Finally, we particularly insist on the perspectives in this
field, through the description and illustration of the systematic use of L-PRF
(Leukocyte- and Platelet-Rich Fibrin) clots and membranes during tooth avulsion,
cyst exeresis or the treatment of gingival recessions by root coverage.
The use of L-PRF also allowed to define new therapeutic principles: NTR (Natural
Tissue Regeneration) for the treatment of periodontal intrabony lesions and
Natural Bone Regeneration (NBR) for the reconstruction of the alveolar ridges.
In periodontology, this field of research will soon find his golden age by the
development of user-friendly platelet concentrate procedures, and the definition
of new efficient concepts and clinical protocols.
 

Fig. (1). Regeneration with L-PRF membranes of 2 maxillary avulsion sockets and cyst cavities. A. The first and second left maxillary molars were compromised because of the destruction of their supporting alveolar bone and a large cystic lesion. B. The 2 molars were avulsed and the cyst was removed carefully. The remaining bone walls were very thin and the bone defects were deep and large, thus presenting a significant risk of incomplete bone healing and fibrous invagination. C. The cyst cavities and alveolar sockets were filled with 4 L-PRF membranes for bone regeneration, and protected with 2 L-PRF membranes for the induction of soft tissue healing and remodelling. D. Tight sutures were performed in order to avoid membrane exposure and the contamination of the large regenerative chamber.	Fig. (2). Regeneration with L-PRF membranes of 2 maxillary avulsion sockets and cyst cavities. A. Six months after the filling with LPRF, the bone defect was completely healed, with no trace of fibrous invagination. B. The regenerated bone volume allowed to place 2 long implants for the replacement of the 2 molars. C. L-PRF membranes were added in order to improve soft tissue healing and remodelling around the implants (multi-induction). D. Sutures were performed. The gingival maturation was already very strong after the first induction 6 months before. E. On the panoramic radiograph, the regenerated bone had the same density and aspect than the natural bone.	Fig. (3). Soft tissue regeneration of a filled avulsion socket protected with L-PRF membranes. A and B. Radiograph and clinical view of a damaged right second premolar. C. Atraumatic avulsion of the premolar and careful curettage of the bone socket. D. The alveolar socket was filled with a mix of L-PRF and xenogeneic collagenated bone (Gen-Os, OsteoBiol, Tecnoss, Italy) in a 50/50 volumic ratio. E. A L-PRF membrane was folded in 3 layers, tailored and placed above the filled avulsion socket. F. Multiple sutures were performed in order to block tight the L-PRF membrane on the grafted area, and to stabilize the folded membrane edge to edge with the wound borders. The external LPRF layer remained in contact with the oral cavity. G. After 24 hours, the gingival tissue was proliferative, the superficial re-epithelialization on the L-PRF membrane and the wound closure were on progress, triggered by the initial induction. H. After 4 weeks, the filled avulsion socket was completely closed. The induction and merging phases were over, and the tissue started the slow and long remodelling phase that lasted until the complete regeneration of a thick gingival tissue. The avulsion socket was regenerated without the use of GBR membranes, complex incisions, flaps and sutures, and their associated risks of negative outcomes.	Fig. (4). Natural Tissue Regeneration (NTR) around a mandibular first molar. A. The first molar was compromised by a distal deep intrabony lesion, with a probing depth around 16mm. B. The retroalveolar radiograph confirmed that the intrabony lesion almost reached the apex of the distal root. C and D. The intrabony defect was carefully cleaned, and filled with a mix of L-PRF and xenogeneic collagenated bone (Gen-Os, OsteoBiol, Tecnoss, Italy) in a 50/50 volumic ratio, in association with a 0.5% metronidazole solution. E. A L-PRF membrane was tailored in order to cover the filled bone defect and to fit to the narrow interdental space. Another membrane was placed around the tooth in order to increase the gingival healing and remodelling on the mesial area of the flap. F. Deep sutures were performed in order to stabilize tightly the flap. G. The first postsurgical radiograph confirmed the complete filling of the intrabony defect.
Fig. (5). Natural Tissue Regeneration (NTR) around a mandibular first molar. A. Seven days after surgery, the gingival flap presented a typical whitish proliferative aspect: this is the induction phase. B and B?. Two months after surgery, the probing depth was stabilized above 2mm. The gingival tissue showed a typical thick and inhomogeneous surface due to active remodeling. The retroalveolar radiograph confirmed the stability of the intrabony filling. C, D and E. The remodelling of the gingival tissue around the molar was followed and carefully evaluated respectively 4, 5 and 7 months after surgery. The mesial (black circles) and distal (black arrows) interdental gingival tissues continued their slow remodelling and growth triggered by the induction. E?. The retroalveolar radiograph confirmed the stability of the intrabony filling after seven months. F and G. The final prosthetic crown was placed on the molar, with open interdental spaces respecting the remodelling and growth of the interdental gingiva. The periodontal remodelling was then followed during 8 months and 2 years after the surgery, and the gingiva slowly continued its slow evolution and reached a very stable final aspect.	Fig. (6). Natural Tissue Regeneration (NTR) around a maxillary first molar. A. The molar presented a deep intrabony defect, with a probing depth around 10mm. B and C. This lesion was very difficult to treat because the defect was all along the vestibular face of the tooth and extended on the mesial and distal faces of the root. D. The fibrous tissues within the intrabony defect was carefully curetted. The clean intrabony extended cavity was then filled with a mix of L-PRF and xenogeneic collagenated bone (Gen-Os, OsteoBiol, Tecnoss, Italy) in a 50/50 volumic ratio, in association with a 0.5% metronidazole solution. E. Three L-PRF membranes were used to cover the surgical site. Care was taken to envelop also the mesial and distal faces. The leukocyte-rich areas of the 3 membranes were shared between the 3 areas of the lesion: one distal, one mesial and one covering the vestibular face (white arrow). F, G and H. This tooth was carefully controlled at 7, 14 and 21 months respectively, and this follow-up showed a strong remodelling of the gingival tissue, with a thick attached gingiva and a final stable probing depth inferior to 2 mm around this tooth.	Fig. (7). Gingival root covering surgery using L-PRF membranes as grafted tissue around a canine. A. This mandibular canine presented a significant vestibular dehiscence. The classical treatment could be the coronal repositioning of the flap, often associated with a connective tissue graft in order to obtain an adequate height of attached gingiva: on the contrary, it was decided to use L-PRF membranes as sole grafted tissue. B. The partial thickness flap uncovered the deep gingival recession. C. The root surface was decontaminated and treated with a tetracycline solution (yellow). D. Three L-PRF layers were placed on the root, above the cemento-enamel junction, and the flap was then sutured coronally. The flap seemed swollen due to the volume of the 3 L-PRF membranes. E and F. Six months after the surgery, the clinical root covering was stable, high and very natural. The gingival induction and remodelling led to a thick attached gingiva.	Fig. (8). Gingival root covering surgery using L-PRF membranes as grafted tissue around a molar and premolar. A and A?. Limited gingival dehiscences were observed, respetively on a mandibular first molar and 2 mandibular premolars. B and B?. In these simple cases, 2 L-PRF membranes were used as tissue graft per case, and placed on the roots above the cemento-enamel junction before the coronal repositioning of the flap. C and C?. The clinical root covering, respectively after 6 and 9 months, was complete in both cases, with a very natural and thick attached gingiva.
Fig. (9). Natural Bone Regeneration (NBR) in a damaged alveolar ridge. A. On the panoramic radiograph, the second left mandibular molar was compromised due to repetitive infections and critical intrabony lesions. This tooth was supporting a bridge that had to be removed during the avulsion of the molar. B. Clinical view of the alveolar ridge before tooth avulsion. The bridge was cut carefully. Note that the gingival tissue around the molar was weak, with a very limited height of attached gingiva. C. After tooth avulsion, the bone defect was full of fibrous tissues that had to be eliminated. D. The cleaned avulsion sockets were large and their regeneration was very important for the placement of implants in good conditions. Moreover, the alveolar ridge ahead of the alveolar socket was quite resorbed, with a residual bone thickness inferior to 3mm (black arrows): the horizontal regeneration of the ridge was also required for an adequate implant placement.	Fig. (10). Natural Bone Regeneration (NBR) in a damaged alveolar ridge. A. The avulsion sockets were filled with a mix of L-PRF and xenogeneic collagenated bone (Gen-Os, OsteoBiol, Tecnoss, Italy) in a 50/50 volumic ratio, in association with a 0.5% metronidazole solution. B. The same bone/L-PRF mix was then grafted all over the resorbed residual alveolar ridge ahead of the avulsion socket. C. Four L-PRF membranes were then used to cover the whole bone regenerative compartment. D. Deep sutures were performed. Because of the grafted volume, an excessive traction of the flap would have been required for a complete closure of the surgical site: in order to keep the gingival flap in an apical natural position, the vestibular and lingual flaps were not sutured edge to edge. The external L-PRF layer remained partially in contact with the oral cavity. E. Eight days after the surgery, the induction phase was almost finished, the gingival tissue was still highly proliferative and starting the merging phase between the gingival connective tissue and the L-PRF layers. The swollen aspect due to the bone graft and the thick layer of L-PRF had considerably diminished. Note that postsurgical pain and edema were minimal. F. Six months after the surgery, the alveolar ridge seemed correctly healed. The gingiva was thick and homogeneous. G. A retroalveolar radiograph confirmed the complete filling of the bone defects. The radiologic bone density seemed homogeneous on the whole area, the previous bone defects were no more detectable after 6 months. H. During the implant placement, the regenerated alveolar ridge was reopened and checked. The attached gingival tissue was very thick (white arrow) and the narrow alveolar crest became a thick bone ridge with more than 5mm in thickness (black arrows). The regenerated area was perfect for esthetic and functional implant placement.
	Fig. (11). Combination of Natural Bone Regeneration (NBR) and Natural Tissue Regeneration (NTR) in a damaged alveolar ridge. A and B. The right mandibular first and second molars were compromised by deep intrabony lesions associated with the osteonecrosis of the bone interdental septum (black circle). C. The second molar was avulsed and the necrosed bone was carefully curetted, leading to a criticalsized bone defect, extended on the whole distal face (and also partially on the vestibular and lingual faces) of the root of the first molar. This molar was not avulsed but was compromised, since the osteonecrosis had destroyed the periodontal bone support down to the apex. D. The extended bone defect was filled with a mix of L-PRF and xenogeneic collagenated bone (Gen-Os, OsteoBiol, Tecnoss, Italy) in a 50/50 volumic ratio, in association with a 0.5% metronidazole solution. E. Bone compartment was covered with 4 L-PRF membranes. Care was taken to envelop with the membranes the grafted area around the distal root of the first molar. F. Tight sutures were performed. G. Three months later, during the implant placement, the regenerated alveolar ridge was reopened and checked. The regeneration of the bone necrosed area (by NBR) and of the periodontal tissues supporting the compromised first molar (by NTR) seemed optimal. H. A retroalveolar radiograph confirmed the complete bone and periodontal regeneration up to an almost natural level (yellow line). Note that after 3 months, the bone compartment was clinically regenerated, but still not completely mineralized since the bone density on the radiograph was still lower in the regenerated area than in the normal bone around.

AUTHORS

Alain Simonpieri,
Marco Del Corso, Alain Vervelle1, Ryo Jimbo, Francesco Inchingolo, Gilberto
Sammartino and David M. Dohan Ehrenfest