Bone grafts can be autogenous, allogeneic, xenogeneic, or alloplastic. Autogenous grafts are taken from a patient’s rib or iliac crest allogeneic grafts are harvested from donors, while xenografts come from different species, typically pigs or bovines. Alloplastic grafts are synthetic and made from minerals similar to bone (Kumar et al., 2013). Calcium Phosphates (CaP) are minerals containing Ca₂₊ cations and inorganic phosphate anions, and are the main minerals in bone and tooth enamel, thus they are favored in regenerative surgery (Terzioğlu et al., 2018; Ma et al., 2023; Eliaz and Metoki, 2017). Commonly used CaP in clinical settings include hydroxyapatite (HA), tricalcium phosphate (TCP), and biphasic calcium phosphate (BCP) (Gao et al., 2017). Among the studies, different PRF and CaPs composites are the most frequently studied.

Multiple in vitro studies show that combining PRF with allogenic, alloplastic, and xenogenic bone substitute materials (BSM) enhances angiogenic, non-cytotoxic, and osteogenic properties (Blatt et al., 2021a; Blatt et al., 2021b; Kumar et al., 2021; Kumar et al., 2019) Table 1. I-PRF with these bone grafts reduces early platelet-derived growth factor (PDGF) release up to two-fold compared to A-PRF (Blatt et al., 2021a). L-PRF improves cell viability, proliferation, migration, and extracellular matrix formation on alloplastic and xenogenic BG, with higher PRF concentrations yielding better effects (Blatt et al., 2021b). L-PRF combined with dentin chips induces higher dentin sialophosphoprotein expression in primary human dental pulp stem cells (DPSCs) compared to L-PRF with nano-hydroxyapatite (nHA), although nHA + L-PRF induces higher DPSCs mineralization L-PRF with dentin chips (Girija and Kavitha, 2020). Kumar et al. found that mixing cut L-PRF membrane with biphasic calcium phosphate (BCP) inhibits the mitogen-activated protein kinase (MAPK) signaling pathway, reducing osteoclastic effects and osteoclast differentiation (Kumar et al., 2021; Kumar et al., 2019). Combining I-PRF with allogenic, alloplastic, and xenogenic BG results in up to a two-fold increase in new blood vessel formation within 24 h compared to native materials, attributed to elevated PDGF levels. This can be attributed to the authors' findings of elevated Platelet-Derived Growth Factor (PDGF) levels in these instances (Blatt et al., 2021a). Higher PDGF-D concentrations (100 ng/mL) enhance endothelial progenitor cell migration, adhesion, and tube formation (Zhang J. et al., 2019). Additionally, mixing nHA or dentin chips with L-PRF increases the radiopacity of the platelet concentrate, making it more visible in X-ray imaging. (Mahendran et al., 2019).

In vivo studies on animal models such as sheep, pigs, rats, rabbits, and dogs have shown that combining PRF with various calcium phosphate (CaP) bone grafts enhances osteoblast activity and accelerates new bone tissue formation, thereby reducing healing time (Abdullah, 2016; Yilmaz et al., 2014; Alkafarani and Baban, 2019; Pascawinata et al., 2023; Şimşek et al., 2016; Nacopoulos et al., 2014; Shevchenko and Rublenko, 2022; Acar et al., 2015; Bölükbaşı et al., 2013). For example, using L-PRF and BCP sticky bone to fill bone defects in sheep resulted in 42% defect coverage by new bone on day 20% and 54.9% on day 40, compared to 29.6% and 49.1% for BCP alone (Bölükbaşı et al., 2013). Similarly, Hwan Jung et al. found that L-PRF mixed with dentin powder improved implant stability and increased regenerated bone area and bone-to-implant contact after 8 weeks (Hwan Jung et al., 2020). Yuan et al. show that PRF in combination with deproteinized bovine bone mineral (DBBM) had higher osteoclast activity than just DBBM in a canine model (Yuan et al., 2021). In rabbits, L-PRF combined with autografts and xenografts promoted faster new bone formation after 8 weeks, though this effect was not observed with β-tricalcium phosphate (β-TCP). (Karayürek et al., 2019). Additionally, some studies show that PRF does not improve healing time when combined with graft materials (Park et al., 2023; Knapen et al., 2015; Lee et al., 2021; Kamal et al., 2017). Knappen et al. observed similar healing patterns in rabbit calvaria between L-PRF, bovine HA, and their combination at early time points of 1, 5, and 12 weeks (Knapen et al., 2015).

Clinical trials testing PRF combined with graft materials for bone defects have been conducted since 2010 (Inchingolo et al., 2010). Multiple studies have since shown that PRF with BSM accelerates dental implant stabilization and tissue healing after sinus lifts, ridge preservation, or bone augmentation have shown positive results in various in vivo studies and case reports (Ramamurthy et al., 2022; van Orten et al., 2022; Tiwari et al., 2020; Pichotano et al., 2018; Amam et al., 2023; hamuda et al., 2023; Simone et al., 2018; Massuda et al., 2023; Caramês et al., 2022; Alberto et al., 2020).

Residual bone grafts also tend to degrade quicker when BG is combined with PRF (Nizam et al., 2018). Pichotano showed that after L-PRF + DBBM usage in maxillary sinus augmentation, the residual bone graft material significantly reduced after 4 months in the test group (3.59% ± 4.22%) compared to the control group (13.75% ± 9.99%) with only DBBM in 8 months (Pichotano et al., 2019).

In clinical human studies and case reports, sticky bone is one of the most studied PRF and bone graft composites. Sticky bone is widely used for severe bone defects in maxillofacial surgery, which are summarized in Figure 2 (Elkholly et al., 2022; Deenadayalan et al., 2015; Hiremath et al., 2014; Lei et al., 2019; Pradeep et al., 2016; Shivashankar et al., 2013; Lorenz et al., 2018) Feng et al. described that using I-PRF with minced PRF clot for sticky bone preparation shortened solidification time, improved tensile resistance, and prolonged degradation time compared to sticky bone made with each PRF type separately. This preparation method provides a more moldable material for filling difficult bone defects (Feng et al., 2022).

Reports on the efficiency of PRF and biomaterial combinations for extraction socket wound healing are often contradictory. PRF improves healing when combined with β-TCP, but not with BCP. Ponte et al. found that sticky bone made with I-PRF and BCP induced slower new bone formation in 8 months compared to PRF clot or BCP alone, although earlier time points were not tested (Ponte et al., 2021). In contrast, β-TCP mixed with PRF clot improved bone density (620.0 ± 31.02) in 6 months compared to PRF (336.6 ± 66.65) or β-TCP (466.0 ± 38.24) alone and helped sustain alveolar ridge bone height and width (Mbarak et al., 2023). Similarly, β-TCP mixed with L-PRF is more efficient in socket wound healing than β-TCP mixed with platelet-rich plasma in parameters like alveolar bone width, height resorption, and bone density (abou shabana et al., 2023).

In 2019, Clark et al. (2018) noted that a combination of A-PRF and freeze-dried bone allograft (FDBA) for ridge preservation resulted in lower bone mineral density compared to FDBA alone. However, histology showed more vital bone volume with A-PRF and FDBA than with FDBA alone. For horizontal ridge defect treatment, better results are suggested when the sticky bone is made from a mineralized plasmatic matrix rather than L-PRF, showing increased bone surface area, osteopontin expression, and reduced collagen amount by bone maturation (Anwar and Hamid, 2022). Additionally, Maia et al. observed that covering a defect with collagen membranes can reduce the healing efficiency of L-PRF and BSM composites (Maia et al., 2019).

Literature on PRF and bone graft composites for intrabony defects have previously been summarized in multiple specific to this disease-focused meta-analyses and systematic reviews and thus will not be reviewed in this article (Pepelassi and Deligianni, 2022; Ye et al., 2023; Theodosaki et al., 2022). Shortly, 2022 systematic review by Theodosaki et al. (2022) noted that PRF added to inorganic bone grafts (BG) offers small improvements in healing size but faster healing time. Pepelassi and Deligianni (2022)Pepelassi et al. (2022) found that using L-PRF with osseous grafts reduces probing pocket depth and radiographic defect depth while improving clinical attachment levels in endosseous and class II furcation defects for non-smoking chronic periodontitis patients. However, a 2023 meta-analysis by Ye et al. (2023) showed insignificant differences in clinical outcomes between PRF + biomaterials and biomaterials alone. Couple of systematic reviews and meta-analyses focusing on PRF and bone graft adjunctive usage in sinus augmentation noted that this method has inconclusive results. Significant drawbacks in clinical studies include unstandardized PRF preparation protocols and short follow-up periods (Alotaibi et al., 2020; Liu et al., 2019).

Another synthetic bone substitute is bioactive glass, which promotes integration with living cells and facilitates the healing process by bonding both to soft and hard tissue by partly converting to hydroxyapatite (Bi et al., 2013; Wilson and Low, 1992). Bioactive glass is composed of minerals like SiO₂, CaO, Na₂O, and P₂O₅ (Hench et al., 2000). Available in various forms—particulate, powder, mesh, and cones—it can be molded to suit different needs and thus is used for bone reconstruction in maxillofacial surgery (Krishnan and Lakshmi, 2013; Han et al., 2020). However, bioactive glass and PRF combinations have been less studied than CaP material composites.

A few studies have tested PRF clots combined with bioactive glass for intrabony defects, showing positive effects (Agrawal et al., 2017; saravanan et al., 2019) (Table 2). Agrawal’s 2017 study mixed L-PRF with calcium phosphosilicate putty for filling intrabony defects, observing significantly better defect bone fill in the L-PRF + bioglass group compared to the bioglass group alone after 6 months. However, L-PRF + bioactive glass treatment had insignificant changes in pocket depth, clinical attachment level, and gingival recession compared to bioglass (Agrawal et al., 2017). Other studies also indicated that L-PRF + bioglass has similar efficiency to bioglass alone for treating intrabony defects or gingival recession (Vibhor et al., 2021). Vibhor et al. (2021) study found no statistical differences in treatment efficiency between bioglass and bioglass with L-PRF after three and 6 months postoperatively.

Polycaprolactone (PCL) is a semicrystalline, biodegradable polymer derived from petrochemical products (Bezwada et al., 1995). PCL is used for drug delivery and for tissue engineering (e.g., bone, blood vessel, cartilage) due to its non-toxicity, biocompatibility, and long degradation time of 2 to 3 years but it lacks hydrophilic functional groups thus inhibiting cellular growth (Engelberg and Kohn, 1991; Malikmammadov et al., 2018; Fu et al., 2012). Therefore, to enhance biocompatibility, PCL materials are often coated with growth factors or synthetic peptides (Zhang et al., 2009; Qin et al., 2022). In maxillofacial surgeries PCL is used for bone reconstructions in maxilla and mandibulae (Hwang et al., 2023; Naik et al., 2020).

Growth factors from PRF can enhance the biocompatibility of PCL biomaterials (Fernandez-Medina et al., 2023; Al-Maawi et al., 2021). Although hydrophobic, PCL scaffolds can physically bind growth factors on their surface, but the protein absorption quantity depends on material surface roughness and hydrophilicity which depends on the manufacturing process (Khampieng et al., 2018; Shen and Hu, 2021). Fernandez-Medina et al. demonstrated that leukocyte platelet-rich plasma (L-PRP) and I-PRF can induce different protein bindings on PCL surfaces. When immersed in I-PRF, PCL surfaces initially bind high molecular weight (>90 kDa) proteins, which gradually desorb and are replaced by middle-low (50–30 kDa) and low (<30 kDa) molecular weight proteins, such as IL-8, eotaxin, IP-10, and RANTES. Conversely, PCL surfaces coated with L-PRP show stable binding of middle-low and low molecular weight proteins like the γ- and β-chains of fibrinogen, which can induce pro-inflammatory processes (Fernandez-Medina et al., 2023; Luyendyk et al., 2019). PCL scaffolds coated with I-PRF have superior protein corona formation compared to those coated with pure platelet-rich plasma, L-PRP, or plasma, indicating better bioactivity. Notably, the presence of a CaP coating on the PCL surface did not affect the protein corona formation when I-PRF was applied (Fernandez-Medina et al., 2023). The method of PRF production plays a crucial role in the effectiveness of PCL-PRF composites. Al-Maawi et al. (2021) found that PCL meshes coated with I-PRF prepared using a low centrifugation method (44 × g) resulted in higher human primary osteoblast adherence after 7 days compared to a high-speed centrifugation method (710 × g). The low-speed PRF composite released twice as many growth factors over 3 and 7-day periods and promoted higher ALP expression from primary osteoblasts seeded on the PCL scaffold (Table 5).

The limited number of extensive in vivo studies on PCL and PRF composites limits the understanding of their overall effect. One study showed that even after the addition of L-PRF the surrounding bone tissue of rat calvaria did not adhere to these scaffolds and used connective tissue to attach to it. The same report stated that the addition of PRF on PCL has the same effect on new bone formation as native PCL. Their PRF preparation method involved a high-speed centrifugation method (1,670 × g), which could explain the reduced biocompatibility (Chen et al., 2021). Verma et al. (2014) showed that PCL with PRF promotes early bone healing in peri-implant defects. However, this study lacked a control group with native PCL or PCL with a different coating, making accurate interpretation of results difficult.

Collagen is the most abundant protein in the human body, providing a scaffold for cells and aiding in the transfer of internal and external forces (Meyer, 2019). There are over 27 types of collagens in vertebrates, with type I collagen being the most common in skin, bone, and tendon (Birk and Bruckner, 2005). Gelatin, a collagen derivative, is a biodegradable and biocompatible protein produced by hydrolyzing collagen’s triple helical structure into random coiled domains, resulting in a molecular structure similar to collagen (Shoulders and Raines, 2009; Davidenko et al., 2016). In maxillofacial surgery, collagen is used as a membrane for creating a barrier between soft and bone tissue, scaffolds for dental pulp regeneration and gelatin sponges are used as a space filler and a hemostatic absorbent (Shabat and Yousif, 2021; Debel et al., 2021; Sheikh et al., 2017).

Commercially available collagen membranes interact differently with I-PRF – for example, membranes with smaller pore sizes restrict the flow of PRF through its layers. This results in lower PRF absorption and shallower cell penetration in the material (Al-Maawi et al., 2019). However, collagen-based matrices with loosely arranged fibrils create a porous structure that allows PRF and its cells to be more easily absorbed (Udeabor et al., 2020). It is worth noting that no studies have described how this PRF absorbability affects cytokine release.

Studies show that when commercially available non-cross-linked equine-derived collagen hemostatic sponge is soaked with I-PRF it prolongs the cytokine release by 6 days, but induces proinflammatory cytokine release from PRF (Herrera-Vizcaíno et al., 2020). Compressing A-PRF+ with a collagen membrane, however, results in the highest growth factor release within 24 h (Blatt et al., 2020). Two studies by Blatt et al. (2020) have shown varying results with PRF and collagen combinations (Sebastian et al., 2022). In 2020, they found that pressed PRF (177 × g for 8 min) combined with three different porcine collagen membranes led to more new blood vessels and branching points than native materials (Blatt et al., 2020). In 2022, they reported that porcine- and bovine-derived membranes combined with PRF (177 × g for 8 min) had the same impact on new blood vessel formation as native membranes after 72 h (Sebastian et al., 2022). Hoda et al. (2021) showed that a three-collagen membrane incubated with A-PRF for 2 h increased gingival fibroblast adherence threefold and human osteosarcoma adhesion twofold. This effect was not seen with cell-free human dermal matrix or porcine-origin collagen matrix. A separate study by Park et al. (2018) showed that the addition of L-PRF to a porcine-derived collagen matrix significantly improves cell activity and mature endothelial cell migration by almost 8-fold.

In vivo studies and case reports show that I-PRF-soaked collagen matrices provide better results for gingival recession, extraction sockets, and sinus floor augmentation (Santamaria et al., 2023; Michels et al., 2023; Gülşen and Dereci, 2019) (Table 6). For gingival recession treatment, collagen membranes soaked with I-PRF achieved higher overall root coverage by 9.3% after 1 month, 15.6% after 3 months, and 13% after 6 months compared to native membranes (Patra et al., 2022). In another instance, Pandikanda et al. successfully treated oro-antral communication using minced L-PRF mixed with a collagen sponge, resulting in no complications and sustained vestibular depth (Pandikanda et al., 2019).

Compared to collagen membranes, there are fewer reports on gelatin in combination with PRF. Gelatin gels can effectively carry growth factors from PRF and prolong the growth factor release in the surrounding environment. (Suzuki et al., 2013; Mu et al., 2020). Gelatin nanoparticles (GNPs) are inherently fragile, with a compressive modulus of 9.2 ± 2.7 kPa and a tensile modulus of 14.1 ± 3.1 kPa. However, adding I-PRF to the hydrogel enhances its resistance to compressive (32.7 ± 4.6 kPa) and tensile forces (Elastic modulus 25.3 ± 4.1 kPa). These composite hydrogels exhibited self-healing and shear-thinning properties, making them suitable for injections before complete solidification. In a rabbit model for sinus augmentation, the GNP I-PRF composite led to significantly more new bone formation, better lamellar bone maturation, and improved new bone height and area compared to GNP gel alone over 8 weeks (Mu et al., 2020). Similarly, Yuan et al. (2021) observed that GNPs + I-PRF could be smoothly injected and maintained their form in water for 72 h even after shaking. The 20 w/v% GNPs in I-PRF hydrogel showed the highest toughness, with a yield stress of 33.2 kPa compared to 15 w/v% and 12 w/v% gels. This combination also resulted in higher bone density and blood vessel percentage area of the alveolar ridge in a canine model compared to DBBM and DBBM with PRF. Additionally, positive results were obtained when gelatin sponge pieces were combined with L-PRF for furcation defect treatment, showing improvements in horizontal and vertical clinical attachment and probing pocket depth. However, the study did not include a control group of only gelatin sponges without PRF, making it difficult to assess the specific impact of PRF (Ahuja et al., 2022).

In nature, silk is produced by certain lepidopteran larvae like silkworms, spiders, scorpions, and flies. Silk fibroin is made of repetitive protein sequences and composed of β-sheet structures (Bini et al., 2004). Silk biomaterials can be improved via amino acid side chain modifications or combining it with different biomaterials, thus allowing for broader applications. These types of materials are biocompatible and useful in wound healing and tissue engineering of bone, cartilage, tendon, and ligament (Vepari and Kaplan, 2007). Although silk is mostly used for sutures, some research groups are using silk proteins to produce scaffolds, hydrogels, and films for tissue repair (Holland et al., 2019).

Since 2013 only one study has investigated PRF combinations with silk biomaterials. This study done on patients showed similar results for implant stability quotients at 3 months between silk fibroin powder + cut PRF clot (type not specified) and PRF alone (57.0 ± 5.29 vs. 58.6 ± 4.95, respectively), but after 6 months the implant stability quotients for silk fibroin + PRF group (76.8 +/−3.65) was significantly higher than PRF (66.80 +/−5.79). Authors observed that bone density after 6 months was significantly higher with Silk fibroin + PRF (418.8 ± 181.3) compared to PRF (345.5 ± 179.5) (Ramy Salah et al., 2021). Although studies show that Silk fibroin with PRF has the potential to help in new bone regeneration studies comparing this composite to native silk fibroin are needed.

Composite materials with inorganic compounds typically consist of polymers like collagen, gelatin, PLGA, and PCL, combined with an inorganic phase such as CaP or metals. This review summarizes 13 studies (Table 7), focusing on the combination of PRF with these materials. The most common method is mixing PRF with CaP to create sticky bone (Peker et al., 2016; Zhang Yue et al., 2023; Bastami et al., 2022), followed by coating synthesized scaffolds via impregnation (Zheng et al., 2015; Espitia-Quiroz et al., 2022) electrically binding to microspheres, or layering in multilayer scaffolds (Zhang L. et al., 2019; Alhasyimi et al., 2017; Alhasyimi et al., 2018; Zhang L. et al., 2023). The impact of PRF on the mechanical properties of these biomaterials is rarely documented. Tarif et al. reported that decellularized PRF coating on strontium-doped porous magnesium phosphate scaffolds did not affect the ultimate compressive strength (Tarif et al., 2023). Beiranvand et al. observed that I-PRF and hydroxyapatite (HA) coating enhanced the hydrophilicity of 3D-printed PCL scaffolds. They also found that platelet concentrate improved preosteoblast viability, doubling cell proliferation after 7 days, and increased RUNX2 gene expression on PCL/HA/PRF scaffolds after 14 days compared to PCL/HA scaffolds (Beiranvand et al., 2022). Similar improvements in cell viability were noted on nHA/PLGA scaffolds impregnated with PRF growth factors, L-PRF-coated HA scaffolds combined with collagen and PLGA copolymer, and L-PRF incorporated into a triple-layer scaffold consisting of an electrospun PCL/gelatin top layer and chitosan/poly (y-glutamic acid)/nHA hydrogel bottom layer (Zhang L. et al., 2019; Zhang L. et al., 2023).

Results from in vivo studies suggest similar results. Only two studies showed that the addition of PRF does not improve new bone formation - Peker et al. studied sticky bone made from collaginated bone graft and L-PRF and deproteinized bone graft with PRF for sinus floor augmentation. The authors saw insignificant differences between groups with and without PRF (Peker et al., 2016). Similarly, Bastami et al. (2022) found only slight, insignificant changes in bone defect healing in sheep using sticky bone made with multi-welled carbon nanotubes, HA, and minced PRF clots. In contrast, Alhasyimi et al. (2017); Alhasyimi et al. (2018) demonstrated that gelatin, carbonated HA, and A-PRF injectable hydrogel retain tooth position longer after orthodontic appliance removal by improving osteoblast activity and inhibiting osteoclast activity. Zhang L. et al. (2019); Zhang L. et al. (2023) triple-layer scaffold, consisting of an electrospun PCL/gelatin top layer and a chitosan/poly (y-glutamic acid)/nHA hydrogel bottom layer, showed enhanced healing in rat and New Zealand white rabbit models, with increased new bone tissue formation, higher OPN protein expression, and improved organization and collagen deposition in histological analyses. Additionally, in vivo studies observed quicker degradation of graft materials when PRF was used (Zhang Yue et al., 2023; Bastami et al., 2022). This could be due to the cell-mediated degradation of CaP materials and the PRF-induced promotion of cell migration, leading to faster biomaterial phagocytosis (Chi et al., 2019; Tajvar et al., 2023). Despite the lack of detailed information on the mechanical properties of these scaffolds, the overall results suggest that PRF serves as a beneficial growth factor source, enhancing the osteogenic effects of composite scaffolds.

For polymer-polymer composites, PRF has been incorporated during the fabrication process, similar to the methods shown in Figure 1. Analysis of the mechanical properties of these composites (Table 7) reveals varied effects. Out of five studies on different polymer-based compositions, three reported that adding PRF to biomaterials reduced mechanical durability (Chi et al., 2019; Noohi et al., 2023; Ansarizadeh et al., 2019). However, a PCL/chitosan core-shell fiber scaffold loaded with L-PRF showed increased tensile strength and elastic modulus (Rastegar et al., 2021). Incorporating PRF during scaffold fabrication often results in significant morphological changes. For example, adding decellularized L-PRF into gelatin and chitosan scaffolds, as well as L-PRF into electrospun nanofibers made from polyvinyl alcohol and sodium alginate, increased pore size (Chi et al., 2019; Nie et al., 2020), but L-PRF incorporation into PCL/chitosan core-shell fibers increased scaffold porosity (Rastegar et al., 2021). In contrast, adding PRF extract to methacrylated collagen (ColMa) and methacrylated gelatin (GelMa) hydrogel reduced both pore size and porosity (Noohi et al., 2023). Chi et al. (2019) observed that PRF improved the chitosan/gelatin scaffold water absorption, Noohi et al. (2023) found that PRF extracts reduced ColMa/GelMa hydrogel shrinkage, but Rastegar et al. (2021) noted that L-PRF decreased scaffold swelling ratio.

In vitro testing of all the polymer composites with PRF demonstrated positive results, boosted bone mesenchymal stem cell (BMSCs) proliferation, adhesion, and osteogenic differentiation were shown with chitosan/gelatin/L-PRF scaffolds and collagen/chitosan/lyophilized A-PRF membranes (Chi et al., 2019; Ansarizadeh et al., 2019). ColMa/GelMa/PRF enhanced odontic differentiation in stem cells from apical papilla (SCAP) (Noohi et al., 2023). Electrospun nanofibers from polyvinyl alcohol/sodium alginate and incorporated lyophilized L-PRF demonstrated better preosteoblast proliferation and osteogenic differentiation compared to nanofibers without L-PRF (Nie et al., 2020).

Although these biomaterials showed positive in vitro results, they lack extensive in vivo testing. Only Chi et al. (2019) tested their material in rat models, where micro-CT analysis showed greater bone volume and formation at 4- and 8 weeks post-implantation. Histological evaluation revealed vascularized bone tissue in groups treated with the chitosan/gelatin/L-PRF scaffold after 8 weeks.

These results show that even though PRF significantly improves biomaterial biocompatibility improving osteogenetic and angiogenetic properties, PRF impairs the mechanical properties of the materials.

3D bioprinting involves layer-by-layer deposition of biological materials to create structures mimicking living tissues or organs. This combines 3D printing with regenerative medicine to construct functional biological structures for medical applications (Mamo et al., 2023) Recently, 3D printing has been applied in bone tissue engineering and dentistry, allowing for precise fabrication of structures with biocompatible materials (Hadad et al., 2023; Haleem et al., 2020) It offers solutions for creating custom-designed scaffolds that mimic natural bone architecture and can improve the mechanical and biological properties of composite biomaterials (Tavoni et al., 2021).

Since 2018, several research groups have integrated PRF into bio-inks for 3D printing, demonstrating promising outcomes for both soft and hard tissue regeneration in animal studies (Table 8) (Sui et al., 2023; Song et al., 2018; Yi et al., 2022; Grandjean et al., 2024). Song et al. and Sui et al. have prepared 3D-printed scaffolds with PRF for mimicking bone tissue (Sui et al., 2023; Song et al., 2018). An alginate-gelatin and I-PRF scaffold designed by Yi et al. (2022) was aimed to help heal oral soft tissue. The enhanced biological properties of these scaffolds likely stem from PRF’s growth factors, which enhance cell adhesion through improved surface hydrophilicity (Bjelić and Finšgar, 2021). Second, Song et al. and Yi et al. noted that the printed scaffolds had rougher surfaces which could be due to the incorporated fibrin (Khampieng et al., 2018). However, incorporating PRF into 3D inks presents challenges. Yi et al. (2022) found that adding fresh I-PRF to alginate/gelatin ink decreased viscosity and reduced scaffold compressive strength, whereas Sui et al. (2023) using lyophilized L-PRF in L-PRF/chitosan/hydroxyapatite bio-ink observed increased viscosity. The viscosity of the bioink is not influenced only by the PRF but also the rest of the components. Crosslinking between PRF and the materials can start even before the printing process, requiring careful optimization through physical-chemical experiments before printing (Yi et al., 2022; Grandjean et al., 2024). The addition of lyophilized L-PRF did not improve the scaffold’s mechanical properties and with the increase of L-PRF concentration in the scaffold compressive modulus reduced (Sui et al., 2023). Song et al. (2018) also observed a similar reduction when incorporating PRF granules into BCP/PVA bio-ink. This means that the improvement of biological properties of 3D printed scaffolds by PRF comes with a cost of the materials’ mechanical properties, which limits the potential uses of the material.