Introduction

Peri-implant tissues and periodontal counterparts have several similarities. However, there are also fundamental differences between these structures in relation to interface biology and etiopathogenesis. This review defines well established peri-implant wound healing concepts and explores site and patient specific factors that may differentially affect early phases of healing and longterm maintenance of regenerated interface between dental implant device and host tissues. It describes variables such as surgical techniques, biomaterials and, implant surface characteristics and fixture design and their possible effect on newly formed interface. Finally, mechanical loading and its differential effect on peri-implant wound healing is discussed.

Peri-Implant Wound Healing

Different Phases of Peri-Implant Wound Healing at Soft and Hard Tissue Levels

Soft and hard tissue healing following surgical placement of dental implants requires a complex cascade of inflammatory and immune responses that take place between implant, alveolar bone and gingival tissue interface. Osseointegration concept was originally described by Branemark et al., 1977 [1] as ‘a direct contact between living bone and dental implant at microscopic level’ and later was demonstrated by Schroeder et al., 1981 [2] as ‘functional ankylosis’. Osseointegration is a dynamic healing process, initiated by primary stability (mechanical) and followed by secondary stability (biological). Primary stability is dependent on mechanical fixation of dental implant, which is promoted by surface macro and micro morphology, roughness, vertical placement in relation to alveolar crest and alveolar bone quality of the site [3]. Whereas secondary stability refers to biological bonding of new alveolar bone to dental implant surface [4]. From a clinical standpoint, the primary stability at time of implant placement is critical since relative micromovement during early healing can lead to early implant failure. Transition from primary stability provided by implant design to secondary stability supported by new bone formation takes place early during wound healing. During this time (approximately from 2 to 4 weeks following implant fixture insertion), implant is most vulnerable to micromovements due to reduced mechanical stability by osteoclastic activity, bone resorption and early phases of bone regeneration as part of bone remodeling/callus formation [5].

Peri-implant osteogenesis can be defined by contact and distant osteogenesis: Contact osteogenesis and de novo bone formation is frequently observed directly on implant fixture surface while in distant osteogenesis, the gap at the interface between implant and alveolar bone is closed by bone healing and bone growth extension from the alveolar bone towards implant fixture surface [6]. The sequence of events at molecular and cellular levels is similar to normal wound healing processes in bone and involves formation of coagulum and granulation tissue, development of provisional matrix, formation of woven and lamellar bone, and remodeling [6,7,8]. A layer of extracellular fluid surrounds implant surface immediately after it is placed in alveolar bone followed by accumulation of intercellular matrix proteins derived from blood. This protein layer is characterized by the implant surface properties and assists cell adhesion, migration and differentiation to implant surface [9]. The void between implant surface and freshly cut alveolar bone is filled with erythrocytes, neutrophils and monocyte/macrophages in a fibrin network. A provisional connective tissue matrix that contains mesenchymal cells, matrix components and newly formed vascular structures replaces fibrin network within the first week. The following healing events can be summarized by accumulation of pronounced woven bone formation by week 2, formation of new mineralized bone extending from prepared bone surface to implant surface by week 4 and bone remodeling process, which take place between weeks 6–12 [10].

At the soft tissue level, wound healing occurs in 3 phases: the inflammatory, proliferative and remodeling phases [11]. While several innate and cell-mediated immune response mediators are activated during inflammatory phase, granulation and epithelial tissue formation are characteristics of the proliferative phase. This later phase is followed by the remodeling of the connective tissue matrix [12]. Development of soft tissue seal around dental implant has been examined in animal studies. The evidence indicates that transmucosal seal around dental implant has similarity to supracrestal attachment of the natural tooth and it stays stable over time [13]. Soft tissue seal around dental implant is impacted by one- vs. two-stage implant surgery [14, 15] by the presence of abutment connection [16] and where the implant-abutment interface is placed in relation to alveolar crest (crestal or subcrestal levels) [17]. In addition, the proximity of an implant to a natural tooth or another implant affects the position of peri-implant hard and soft tissue attachment as well as papilla height [18, 19]. It is well known that epithelial attachment on a titanium surface is less resistant to inflammatory stimuli [20], and presents a higher level of peri-implant soft tissue inflammatory response compared to gingival tissues surrounding adjacent teeth [21]. Matured peri-implant soft tissue is characterized by oral epithelium at the outer surface, sulcular epithelium at the inner surface. The collagen fibers of the peri-implant tissue mostly extend from periosteum of the alveolar bone crest to the gingival margin and, are arranged parallel to the implant surface [22]. Similarly, the vascular structure of the peri-implant tissue solely comes from supraperiosteal vessels [23]. In summary, peri-implant soft tissue characteristics mimics more of a scar tissue following wound healing. Thus, understanding dental implant soft tissue healing concepts and potential limitations allow clinicians to evaluate each case carefully for better clinical outcomes [11]. The number of publications on osseointegration, peri-implant wound healing and the impact of clinical concepts such as surgical techniques, implant surface characteristics, and mechanical loading protocols on various databases is extensive (Fig. 1). Thus, there is a continuous interest on exploring these topics in dental research.

Fig. 1
figure 1

Robust dental implant literature by number of publications, 2000–2023. The figure is created on Feb 12, 2024, by pubmed search tool using Medical Search Heading (MeSH) keywords: Dental Implants, Peri implant endooseous healing, surgical procedure, dental implant loading

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Site and Patient Specific Factors Affecting Peri-Implant Wound Healing

Site Specific Factors

Successful bone healing and osseointegration depends on several factors such as implant design and surface topography, bone quality at implant site, local and systemic health during healing phase and implant loading conditions. Wound healing differential response due to biomaterial characteristics is covered later in this manuscript. Bone quality is as critical as bone quantity when it comes to regeneration and stability of peri-implant interface. Quality of the alveolar bone has been described through several well-established classification systems. Leckholm and Zarb’s bone typing [24, 25], groups quality of alveolar bone from 1 to 4 based on the amount of trabecular and cortical bone observed on panoramic/peri-apical radiographs as well as surgeon’s tactile experience of bone density. Type 1 is described as rich in cortical bone while Type 4 defines soft bone, which is mainly cancellous origin. While cortical bone plays major role in obtaining higher primary stability, it is poor in blood supply, which may negatively affect angiogenesis and tissue regeneration rate at the interface [24, 25]. In addition, higher initial torque forces and related mechanical stress have been discussed as possible causes of peri-implant bone loss during early phases of healing in relation to Type 1 type bone quality [26]. Thus, anatomical location (maxilla vs. mandible and anterior vs. posterior) differentially affects healing outcomes not only due to the amount of the bone and proximity to important anatomical landmarks but also due to the quality of existing bone [27] (Fig. 2). In addition, there is sufficient evidence supporting the higher risk of healing complications at sites with a history of chronic apical infection and/or a tooth with a long-term root canal treatment [28]. Similarly, sites with a history of implant failure represent higher risk of healing complications around implants that replace the original one [29]. There is also growing body of literature on impact of healthy but thin tissue phenotype on long-term peri-implant interface stability [30,31,32]. Thin periodontal phenotype is described as less than 2 mm gingival tissue thickness [31]. While this amount of gingival tissue may be sufficient to protect underlying bone and root surface, recent evidence reports that thicker attached/keratinized gingival unit is necessary for the long-term stability of peri-implant tissues [32].

Fig. 2
figure 2

An early wound healing complication and its management- Implant fixture was surgically placed with two-stage (submerged) approach at an edentulous healed site with no bone grafting history. Wound healing during osseointegration phase was uneventful. 2AB: Immediately before implant uncovery with minor discharge only detected with periodontal probe and no evidence of radiographic bone loss. Patient was asymptomatic. 2CD: Following incision and flap elevation for uncovery. Significant granulation tissue covering the color aspect of the implant. 3 threads exposure and a bony defect with no intact walls discovered following degranulation and decontamination. 2E: radiographic presentation at 2 months post-uncovery. Clinical findings revealed shallow probing depths, absence of BoP, suppuration, and minimal thread exposure with no plaque accumulation. 2F: 1 year in function

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Patient-Specific Factors

Any behavioral, local and systemic conditions could pose a relative risk to implant success by effecting wound healing and host response, which would negatively influence short and long-term peri-implant tissue stability. Active smoking and history of periodontitis are well-accepted risk factors for peri-implant healing complications and peri-implant diseases [33,34,35]. Diabetes Mellitus (DM), osteoporosis and antiresorptive medication usage, radiation therapy are among the most commonly explored patient related risk factors [35,36,37,38]. Studies and systematic reviews indicate that although osseointegration of implants is similar between DM and non-DM patients, the long-term success rates tends to decrease due to higher incidence of peri-implantitis and alveolar bone loss observed in patients with DM [39, 40]. Osteoporosis appears to have the similar impact as DM in which patients present increased rate of peri-implant bone loss in long-term [41, 42]. Literature also highlights the synergistic effect of various health related factors, as each patient may present with more than one co-morbidity. Therefore, comprehensive review of systemic health status and update of the medications should be a routine part of the risk assessment protocol during initial treatment planning phase and at each therapy appointment for any dental implant related procedure. In addition, an in-depth discussion for possible delayed healing and short/long-term complications based on risk assessment tools should be shared with the patient [35, 43, 44].

Healing Outcomes of Non-Surgical and Surgical Peri-Implant Treatments

Periodontal treatment concepts are routinely applied for any non-surgical or surgical intervention following osseointegration period to maintain and/or treat peri-implant tissues. Nevertheless, the presence of an implant device at both hard and soft tissue interfaces creates additional challenges that may negatively affect healing outcomes following these treatment modalities [45,46,47,48,49,50]. The possible effect of mechanical and chemical oral home care on titanium has been recently questioned through in vitro and in vivo studies [45, 46]. Similarly, the effect of dental instruments used in professional dental cleaning procedures has been investigated [47,48,49,50]. Lately, there is a trend to introduce more chemicals, local drugs and/or LASER based non-surgical treatment options to control peri-implant tissue inflammatory responses [50]. Any soft tissue deficiency at implant site can be treated by conventional soft tissue grafting procedures. Free gingival graft is generally preferred to increase vestibular depth together with the amount of attached/keratinized gingiva. However, these grafts heal with more scaring compared to subepithelial connective tissue grafts [48]. Decontamination of the surface through mechanical and/or chemical techniques has been questioned not only in relation to its success in eliminating bacterial challenge but also whether it would negatively affect the integrity of the titanium alloy fixture [50]. Although osseous resective surgeries have more predictable outcomes in eliminating peri-implant pockets, long-term maintenance of treated sites has been controversial due to exposed titanium surface [51, 52]. Radiographic bone fill within the peri-implant infrabony defect rather than re-osseointegration of the grafted material on the decontaminated titanium surface following regenerative approaches is expected and considered as a successful outcome [52, 53]. In summary, there are many unknowns when it comes to peri-implant wound healing following non-surgical and surgical treatment modalities indicated to maintain healthy tissue contours and control the stability of the regenerated tissue-material interface.

Peri-Implant Wound Healing-Differential Response Based on Surgical Techniques

Immediate, Early, Late Implant Placement and Wound Healing Outcomes

Various surgical protocols for implant fixture placement have been developed to shorten the treatment time and improve healing outcomes. Namely, conventional or late protocol is defined as implant placement surgery following post-extraction complete healing of soft tissue and alveolar bone, which would take a minimum of 4–6 months [54]. Early placement protocol requires a minimum of 6 to 8 weeks after tooth extraction which only allows soft tissue healing [55]. This later approach is preferred for those cases who would require alveolar ridge augmentation together with implant placement [55, 56]. On the other hand, immediate implant placement is designed to place the implant fixture at the time of tooth extraction [57]. The basic peri-implant wound healing phases described earlier in this manuscript may be differentially affected based on the chosen surgical technique to place implant fixture. For instance, in early or immediate implant placement surgical protocols, hard and/or soft tissue grafting may be necessary to seal the jumping distance (the space between titanium surface and alveolar bone wall) and/or to compensate the buccal bone resorption due to post-extraction lack of bundle bone [55,56,57,58]. Differential peri-implant wound healing response in the presence of hard or soft tissue grafting materials will be described later, in Section "Peri-Implant Wound Healing- Differential Response Based on Biomaterials".

Two- and One-Stage (Submerged and Non-Submerged) Implant Placement and Wound Healing Outcomes

There is sufficient evidence reporting a differential peri-implant soft and hard tissue healing response between one- (non-submerged) and two-stage (submerged) implant placement protocols [59, 60]. Conventionally, two-piece bone level implant fixtures have been placed by using two-stage approach meaning that the initial phase of osseointegration would occur without exposure to oral cavity [61]. The supporters of this approach have been advocating it especially for sites that have soft bone characteristics, less than ideal primary implant stability and for patients with higher risk of healing complications such as smokers [62]. Recently, placement of two-piece bone level implants by using one-stage protocol received significant support not only to eliminate the need of a second surgery for implant uncovery but also to provide immediate provisionalization [63]. Most importantly, better soft tissue seal has been reported following one-stage approach with permanent abutment placed immediately after implant fixture placement instead of repeated replacement of healing abutments prior to final restoration [64, 65].

Peri-Implant Wound Healing- Differential Response Based on Biomaterials

Grafted/Non-Grafted Sites and Peri-Implant Wound Healing

As previously discussed, bone remodeling following implant placement is based on a complex interplay between host bone and immune system (a phenomenon described as Osteoimmunology) [66]. Depending on the etiology of the tooth loss, post-extraction tissue deficiencies are often treated with bone grafting procedures either prior to or simultaneously at implant fixture placement. This surgical requirement adds a second layer of complexity to peri-implant wound healing [67].

Allograft and xenograft bone graft materials that are used to augment alveolar ridge or alveolar socket prior to implant placement are known to have osteoconductive and some osteoinductive characteristics [68]. Thus, they are generally mixed with each other or with autogenous bone graft to compensate their lack of osteogenesis [69]. New bone forms on the surface of an allograft or xenograft particle while it goes through resorption. However, resorption rate is known to be slow especially for xenograft. Histomorphometry studies performed on obtained bone cores from bone augmented sites report significant residual xenograft material embedded into the newly regenerated bone at the time of implant placement [70]. These materials may be in direct contact to implant fixture surface at the implant/bone interface [71]. The stability of this type of interface has been questioned since it is well known that bone remodeling around mechanically loaded dental implant is a continuous phenomenon for the lifetime of the restoration [4]. Based on recent in vivo studies, a continuous remodeling can be observed with intact osteogenic cells together with the presence of empty lacunae and/or, a continuous balance with active differentiation occurs between osteoblastic and osteoclastic cell lineages [4, 72]. Thus, hypothetically, these residual materials may continue resorbing while subsequent new bone forms around them. But, it is also possible that a space may develop between the implant fixture and resorbing bone particle which may initiate uncontrolled inflammatory response. In general, reports on the effect of bone augmentation in long-term clinical performance of dental implants indicate similar results to non-grafted sites in terms of implant survival and clinical peri-implant parameters [73]. However, occurrence of peri-implant dehiscence type defects following bone augmentation and healing is shown to increase the risk of future peri-implant disease and mucosal recession [74].

In terms of soft tissue response to surgical implant placement, differences in flap blood perfusion rate are detected at previously grafted sites compared to pristine bone ridges [75, 76]. This, in turn, may affect the quality of the soft tissue surrounding the implant-supported restoration and may be an important factor to consider for the long-term maintenance of peri-implant gingival health especially when dealing with thin tissue phenotype [77, 78].

Implant Fixture Surface Characteristics and Peri-Implant Wound Healing

Peri-implant wound healing can be differentially affected by the type of the metal, the design, surface tomography, surface roughness and the titanium oxide content of dental implant fixture. Titanium and titanium alloys (Ti-6Al-V) have been the material of choice for dental implants due to their biocompatibility properties and bioinert characteristics [79]. By definition, biocompatibility means that biomaterial is well accepted by the host without inducing any adverse effect while bioinert means that biomaterial itself will not induce any host response [80]. Presence of a titanium oxide layer on implant fixture more than titanium alloy itself has been introduced as a main player in well tolerance and lack of immune response [81]. This layer is formed as soon as implant is exposed to air and, becomes thicker with time [82]. Osseointegration concept has been revisited with the increase prevalence of peri-implant tissue breakdown [83]. Based on recent studies, titanium implant devices should not be considered as bioinert since the material itself is inducing host response (e.g. Foreign Body Reaction) following its delivery to alveolar bone [84, 85]. Through bone formation to encapsulate the implant, host reaches to an equilibrium, which provides the stability of the interface as well as continuous remodeling at the regenerated bone [66].

Wound healing around dental implant fixtures has been differentially affected by the introduction of various surfaces with different characteristics. Initial machine surface implants have been replaced with surfaces that have higher roughness and porosity with the goal of increasing bone-implant contact surface and, allowing faster and stronger osseointegration [86]. These surfaces are prepared through sand, grit or titanium oxide blasting followed by acid etching and neutralizing or by using discrete crystalline deposition, laser ablation to obtain nanotomography [87]. Recently anodic oxidation technique has been introduced not only to adjust the color of the metal but also to increase both the thickness of titanium oxide layer and surface roughness [88]. This, in turn, has been shown to induce better soft tissue attachment [89].

In summary, a treaded implant geometry enhances primary stability, limits the microenvironment between implant and alveolar bone wall and, provides a greater surface area for osteointegration [90, 91]. While the moderate surface roughness created through sandblasting, acid etching or oxidation provides enhanced osteoblast adhesion, proliferation and differentiation on the implant surfaces [92,93,94]. Animal and in-vivo studies present a strong support for surface modification methods especially during early healing phases of osseointegration, even though rough titanium surface may jeopardize the long-term stability when exposed to pathogenic biofilm. In addition, rough surfaces designed to induce bone regeneration but a possible chronic irritant for gingiva, may not be as beneficial for soft tissue/titanium interface which is critical for long-term stability of peri-implant tissues [95]. Additional research on the development of dental implant biomaterials for better and more predictable clinical outcomes is necessary.

Bone Level and Tissue Level Implants and Peri-Implant Wound Healing

Bone level implants were designed to replace tissue level implant fixtures due to concerns in time dependent deterioration of esthetics with the later [96]. However, bone level implants present their own challenges both during healing and later on, for long-term stability of peri-implant tissues. Specifically, rough/porous surface of titanium alloy extends throughout the implant fixture length in bone level implants and, abutment connection is localized at where this surface ends. Similarly, entire implant fixture is embedded into bone to cover rough/porous surface. Thus, any gap between abutment and fixture connection would be located at alveolar crest level [97]. Such gaps, although less common with better connection designs, would cause extracellular fluid collection and would create perfect niche for biofilm to form [98, 99]. In addition, minor soft tissue inflammation due to plaque accumulation and/or mechanical trauma can induce bone resorption and exposure of rough/porous surface. There is a significant interest in improving abutment designs to induce a better hard and soft tissue seal at implant-abutment connection. One of such innovative approaches is the concept of platforming switching instead of matching [100, 101]. This approach intends to move any possible microgap away from the alveolar crest although reported outcomes of such treatment modality has been controversial [101]. Similarly, submerging bone level implants into bone is a well-established contraindication since this approach would cause an ‘infrabony’ microgap location [16]. However, a recently published work reports prevention of bone loss by combining platform switching concept (narrow abutment) with submerged implant placement (bone level implant fixture placed apical to alveolar crest level) specifically at sites with thin soft tissue phenotype [102].

Nevertheless, the distance between the low-level biofilm induced inflammatory response to alveolar crest is generally shorter with bone level implants. Thus, minimal surface exposure at the crest initiates a chain of reaction causing progression of bone loss along the fixture and increases the risk of biocorrosion [103]. Lately, new implant fixture designs with nanosurface characteristics at the collar region have been developed to induce stronger hard and soft tissue attachment to prevent such problems [104]. Similarly, there is an interest in developing hybrid designs with anionization technique used at the most coronal aspect of the implant fixture to mask metal color showing through gingiva but also to induce soft tissue attachment at this region [104].

Peri-Implant Wound Healing- Differential Response Based on Mechanical Loading

The importance of wound stability for regenerative surgery protocols during healing has been well documented [105]. However, controlled mechanical loading is beneficial for bone healing [106]. Several loading protocols have been developed for dental implant supported restorations (i.e. immediate, early/progressing and late mechanical loading). Higher implant primary stability with intact peri-implant bone support at the time of placement is a prerequisite to consider immediate and/or early/progressing mechanical loading [57]. It is also well documented that implant fixtures would not tolerate forces in lateral directions [107]. Such forces would cause mechanical stress and bone resorption especially at the alveolar crest level even if osseointegration process may not be negatively affected. To control such traumatic occlusion, removable temporary restorations should be avoided during early healing. Similarly, short implant fixtures supporting long crowns are still controversial for long-term success of the implant due to difficulty in controlling lateral forces as well as maintaining oral hygiene around these restorations [108, 109]. When considering the effect of occlusal forces on peri-implant tissues, it is important to anticipate that the occlusal interferences are continuously changing especially in partially edentulous patients since the magnitude of forces in function are different between teeth and implant supported restorations (110, 111). Thus, routine and repeated occlusal analysis/limited occlusal adjustment may be indicated more often in partial edentulous patients restored with implant supported restorations.

Conclusions and Future Directions

Peri-implant wound healing has complex dynamics intense and acute initiation of the host response to surgical trauma which continues with a low dose inflammation induced by various local factors including tissue and biomaterial characteristics. Establishment and long-term maintenance of a stable interface depend on controlling related host response in addition to protecting the continuous bone remodeling phenomena that is observed as a response to functional loading. Thus, the determinants of the clinical outcomes following such complex peri-implant wound healing patterns are multifactorial.