Regarding the effect of the type of additional fixation on the process of bone formation, it is known that intermediate tissues, such as fibrous tissue, cartilage, and woven bone, precede final bone formation, with the mechanical loading affecting the regeneration process and different stress distribution supporting or inhibiting differentiation of particular tissue phenotypes. During the repair and regeneration of periodontal bone defects, it is known that intermediate tissues, such as fibrous tissue, cartilage, and woven bone, precede final bone formation. GBR membranes not only need to withstand the forces generated during surgery but also need more time to cope with the stresses generated by tissue growth and physiological activities (Lacroix and Prendergast, 2002; Tejeda-Montes et al., 2014). In addition, it is necessary to cut and shape the membranes according to periodontal defects with different morphology during the placement of the membranes into the bone defect. At this stage, membrane hardness is of great importance (Rowe et al., 2016). Achieving a balance between stiffness and flexibility in membrane formulations developed for GBR is necessary and important for the success of the GBR procedure (Rowe et al., 2016). Appropriate mechanical strength makes GBR membranes not only prevent membranes collapse from maintaining tissue living space, give full play to its barrier role, but also easy to operate in vivo to avoid damage to surrounding tissues (Bottino et al., 2012). In addition, the mechanical stability of GBR membranes also plays an important role. Studies have shown that micromovements between bone and any implanted material prevent bone formation, resulting in the development of fibrous tissue (Ducheyne et al., 1977). Adequate stability and minimal stress are required to allow the early tissue infiltrating through the pores to differentiate into the bone by direct or appositional bone formation (Gutta et al., 2009). It has been observed that bone formation is significantly enhanced when the resorbable membrane is tightly attached and immobilized to the bone surface (Amano et al., 2004). To maximize membrane stability, the use of membrane-fixing pins has been suggested. However, the corresponding mechanical load on the process of bone formation is due to different additional fixation methods and then affects bone regeneration (Amano et al., 2004; Dimitriou et al., 2012). Studies have shown that high shear strain and fluid flow stimulate fibrous tissue formation, whereas lower levels stimulate cartilage formation, and even lower levels favor ossification (Stetzer et al., 2002). It has been demonstrated in vivo that there is more rapid and more organized new bone formation stimulated by appropriate mechanical load imposed by resorbable CM-covered plate bone internal fixation compared to non-rigidly fixed defects (Stetzer et al., 2002). In addition, the formation of the new vascular network necessary for bone regeneration is affected by mechanical loading, and appropriate stress stimulation promotes vascular remodeling (Boerckel et al., 2011). Many studies have shown that the success rate of GBR surgery in repairing periodontal bone defects is closely related to the membranes’ spatial maintenance ability and stability. Sufficient mechanical strength and stability are the key factors for the effective induction of bone regeneration by GBR membranes (Wessing et al., 2018; Shahdad et al., 2020). The evaluation of mechanical properties includes many aspects, and tensile tests are often used as the first method to obtain information about the mechanical properties of membranes (Zhou et al., 2021; Chen et al., 2022). The tensile strength of pure PCL membrane was 1.63 ± 0.67 MPa. The value of pure fish collagen was 6.72 ± 0.44 Mpa. The maximum tensile stress of common commercial membranes was also different: Bio-Gide (4.8 MPa), Collprotect (13.1 MPa)and Jason (13.0 MPa). GBR membranes that induce periodontal bone regeneration have been reported to have ultimate tensile strength values between 1 and 20 MPa (Ortolani et al., 2015; Moonesi Rad et al., 2019). In addition to evaluating the strength of the membrane, the strain capacity, elastic modulus, and elongation rate of the membrane are also commonly used to assist in the evaluation of mechanical properties. However, increasing the strength usually leads to a decrease in elongation. For example, the Elastic modulus of pure PCL membrane is 0.18 ± 0.04 MPa, and the failure strain is 106.14 ± 23.29. A new type of PCL membrane was prepared by adding Silica Gel to the PCL membrane. The results showed that the strength and elastic modulus of the hybrid membrane containing 40% silica Gel were 5 and 8 times higher than those of the pure PCL membrane, respectively. The failure strain was 28.92 ± 8.41 (Lee et al., 2016). In addition, studies have shown that the thickness of common commercial collagen membranes varies from 0.2 to 0.4 mm. The thickness of the membrane is closely related to the cell adhesion and swelling properties of the membrane, and it changes instably during tissue regeneration. The change of the thickness of the membrane will have a certain impact on the mechanical properties of the membrane. Therefore, relevant comparisons should be made as comprehensively as possible in the evaluation and reinforcement of membrane mechanical properties (Lee et al., 2016; Pouroutzidou et al., 2022).

Recent clinical studies have shown that the hybrid CMs prepared by blending multi-component natural substances can effectively strengthen the membrane’s mechanical properties and ensure its spatial maintenance ability (Luo et al., 2021). Luo et al. (2021) reported that a composite membrane with good mechanical properties was prepared by mixing Silk fibroin (SF) and collagen using green papermaking. Silk fibroin (SF) from Bombyx mori, a versatile natural fibrous protein, has been extensively used in bone tissue engineering applications owing to its low immunogenicity, slow degradability, and feasible mechanical properties (Melke et al., 2016). Studies have shown that a hybrid membrane consisting of a large amount of SF(75%) and a small amount of collagen (25%) can maintain long-term mechanical properties after implantation. SF provides a remarkable combination of strength and toughness to maintain enough stability (Wu et al., 2017). In addition, the collagen content blended with SF membranes can be selected depending on the level of mechanical property and biodegradation time required of the regenerating tissue, then GBR membranes with specific mechanical strength and stability are prepared (Luo et al., 2021). The good mechanical properties of the composite membranes can also be attributed to its new preparation method. Traditionally, the main and common methods such as electrospinning, rapid prototyping, particulate leaching, and solvent-casting have been applied to fabricate GBR membranes (Masoudi Rad et al., 2017; Jian et al., 2019). However, the protein conformation (composed mainly of β-sheet) and the parallel-fibrillar structure of SF fibers may be disrupted by directly solvent casting and electrospinning, resulting in the mechanical degradation of SF membranes (Keten et al., 2010). To overcome this limitation, tannic acid (TA), a low-cost natural polyphenolic compound extracted from plants, was used to modify electrospun SF nanofiber membranes. The large polyphenolic groups in TA were combined with SF protein to induce the conformation of SF molecule into a tight β sheet, and the mechanical properties of SF membranes were successfully improved (Luo et al., 2020; Zheng et al., 2020). In addition, recent studies have reported that there will be less damage to SF molecular structure and better mechanical properties of nanofibers if the nanofibers are extracted directly from SF by the physical shearing method (Ang et al., 2020; Li et al., 2021). Chen et al. (2022) also successfully obtained SF membranes with good mechanical properties through this method. However, collagen cross-linking is the most common way to improve the mechanical properties of the most widely used native CM (Khorsand et al., 2019; Liu et al., 2020). Ahn et al. (2020) directly used 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) with low cytotoxicity as a cross-linking agent and successfully obtained GBR membranes with good mechanical properties. Studies have shown that the interaction between collagen molecules and the structural integrity of collagen molecules have been improved, finally strengthening the mechanical properties of the membranes (Speer et al., 1980).

In summary, the success rate of GBR surgery is closely related to the mechanical properties of GBR membranes in repairing periodontal bone defects. Good mechanical strength and stability can prevent the collapse of GBR membranes to maintain the space for bone regeneration and give full play to the barrier function of membranes, effectively promoting bone formation. In current studies, the mechanical properties of GBR membranes can be effectively strengthened by blending multi-component natural materials, and even the customized mechanical strength and stability of GBR membranes can be obtained by adjusting the ratio of different components. In addition to changing the material formulations of GBR membranes, many studies have proved that the mechanical properties of natural resorbable membranes can also be effectively improved by modifying some compounds, such as TA. Many novel preparation methods, such as physical shear or EDC-collagen cross-linking, can enhance the mechanical properties of natural resorbable membranes. However, although several strategies effectively improve membrane mechanical properties, their clinical performance has not been systematically tested and compared, and further research and testing are still needed.

Similar to CM, most natural polymer-resorbable membranes have the advantage of having a small inflammatory response and no cytotoxicity. However, due to the macrophage and polymorpho-nuclear leukocyte-derived enzymatic activities, the degradation of the barrier membrane starts soon after implantation. The rapid degradation of the barrier membrane results in the inability to achieve its desired barrier effect, which ultimately leads to surgical failure (Mir-Mari et al., 2017; Meyer, 2019). Several studies have shown that membranes’ integrity was well maintained during the first 14 days. However, there is a significant reduction in membrane thickness from 14 to 30 days of healing and a significant reduction in the total amount of collagen. Nevertheless, bone formation was occurring incorporating fragments of the degraded collagen fibers at 30 days (Moses et al., 2008; Kozlovsky et al., 2009). It has been suggested that a 1-month barrier function time for each millimeter of bone regeneration is needed (Guarnieri et al., 2015). Depending on the size of the periodontal bone defects and the graft materials, the time required for bone regeneration and healing varies greatly. Generally, bone grafts in the mouth heal after 3–9 months, whereas larger alveolar bone defects require longer to regenerate and heal (Triplett and Schow, 1996; Laurencin et al., 2006). Ideally, the membranes’ biodegradation rate should match the new tissue formation rate with no residual materials left (Sbricoli et al., 2020). The regeneration rate of bone tissue is much slower than that of connective tissue in periodontal bone defects. Hence, the barrier membranes’ degradation rate should match the bone healing rate. In order to provide mechanical support during bone formation, the integrity and stability of membranes should be guaranteed in the range from 4 weeks, when the bone remodeling phase starts, up to several months (Sánchez-Fernández et al., 2021). The degradation time of natural resorbable membranes depends on the tissue origin and manufacture process. For example, Collatape, made of bovine collagen, presents a barrier effect of 1–2 weeks, whereas Botiss Jason, made of the porcine pericardium, and Copios Extend, made of the porcine dermis, present a barrier effect of 8–12 and 24–36 weeks, respectively (Sbricoli et al., 2020). To improve the degradation resistance and prolong the barrier effect of CM and other natural resorbable membranes, researchers have proposed various methods, such as cross-linking or larger and thicker membranes (Jiménez Garcia et al., 2017). Multiple studies have cross-linked existing collagen fibers based on physical (UV irradiation), chemical (glutaraldehyde, hexamethylene diisocyanate, diphenyl phosphoryl azide), and enzymatic (ribose) interactions produce resorbable cross-linked CM effectively improving CM persistence (Petite et al., 1994; Olde Damink et al., 1995; Weadock et al., 1995; Behring et al., 2008; Aprile et al., 2020). Moses et al. (2008) reported that the improvement of the persistence of cross-linked CM may be due to its resistance to enzymatic degradation during bone regeneration, and the persistence of CM is prolonged with the increase of cross-linking ratio. However, the enzyme activity in the tissue may increase under pathological conditions, affecting the regeneration of bonePLA, PCL tissue in the defect area and leading to accelerated CM degradation (Eliezer et al., 2022). Several studies have shown that compared with normal rats, the inflammatory infiltration in CM of diabetic rats is more obvious, and the number of macrophages and endothelial cells is significantly increased (Eliezer et al., 2013; Moses et al., 2016). These cells also can secrete the matrix metalloproteinase. While the activity of these proteinases likely contributes to both the host defence function of macrophages and normal tissue remodeling and repair (Campbell et al., 1991), various reports have shown that it is also the main reason for the accelerated degradation of CM (Moses et al., 2016). Eliezer et al. (2022) showed that compared with non-immersed CM, the degradation of CM could be delayed, which is immersed in cross-linked high molecular weight hyaluronic acid (CLHA) for type 1 diabetic rats. Hyaluronic acid is a natural glycosaminoglycan. It is an essential component of connective tissues and plays an important role during wound healing (Croce et al., 2001). CLHA can reduce the production of inflammatory cytokines such as interleukin (IL)-1β, showing anti-inflammatory effect (Mitsui et al., 2008). The reason for this is likely linked to a phenotypic switch macrophages undergo when they are in contact with Hyaluronic acid. M1 macrophages mainly play a role in pro-inflammatory and immune clearance by secreting pro-inflammatory factors, thereby killing pathogens and tumor cells. M2 macrophages are mainly involved in anti-inflammatory and wound healing by secreting anti-inflammatory and growth factors. Promoting phenotypic polarization of M2 macrophages can effectively promote angiogenesis and bone healing. Macrophage phenotypes depend on the molecular weight of HA. At LMW of HA, macrophages have pro-inflammatory response and at HMW of HA, macrophages have anti-inflammatory and pro-resolving responses. Therefore, the immersion of CM in CLHA before implantation may slow down the degradation of CM by reducing the number of infiltrating macrophages, thus prolonging the maintenance time of CM thickness and collagen density, then better preserving the barrier function of CM (Eliezer et al., 2022). In addition to reducing the release of enzymes directly by reducing the number of inflammatory factors such as macrophages by anti-inflammatory substances, reducing the susceptibility of native membranes to enzymatic degradation by macrophage-released lysozyme can also slow the rate of membrane degradation. Murali et al. (2021) prepared modified electrospun CM including acetic anhydride (AA) and hexanoic anhydride (HA) using electrospun chitosan membranes (ESCM) modified with short-chain fatty acids. Studies have shown that compared with HA membranes, AA membranes are more hydrophilic and able to absorb more fluid, leading to more cell infiltration and faster membrane degradation. HA membranes have a slower degradation rate which will lead to a better barrier effect. HA membranes are more suitable for the regeneration of large periodontal bone defects. This may be due to the increased hydrophobicity of the membranes with increasing length of short-chain fatty acids, which slows the hydrolysis of HA from the polymer chains thereby reducing their susceptibility to enzymatic degradation by macrophage-released lysozyme (Murali et al., 2021).

In summary, GBR membranes must have a degradation rate that matches bone tissue formation to achieve effective regeneration of periodontal bone defects. It is of great significance to select the appropriate material sources and preparation methods for applying GBR membranes to promote bone regeneration because the degradation rate of natural polymer absorbable membranes is affected by the origins and manufacturing process of the tissue. In addition, the material sources of the natural membrane itself, the natural structure and properties, and the properties of the surrounding environment have an important impact on membrane degradation. It is the most common and effective way to improve the degradation rate of natural polymer membranes by using different degrees of collagen cross-linking to enhance CM’s molecular structure and enzymatic degradation resistance. However, the internal environment of the tissue under pathological conditions causes many inflammatory cells to infiltrate into the implanted GBR membranes, leading to rapid membrane degradation. Studies have shown that improving the hydrophobicity of membranes by anti-inflammatory factor infiltration or short-chain fatty acid molecular modification can effectively reduce the release of inflammatory factors or improve their susceptibility to enzymatic degradation, ultimately achieving the improvement of membrane degradation rate. However, the clinical application of these membranes needs to be further evaluated, such as their potential to induce bone healing in the presence of graft materials or periodontal bone defects of different sizes.

In contrast to the enzymatic degradation of native membranes, synthetic membranes are often reabsorbed by non-enzymatic (hydrolytic) cleavage to form pyruvate and lactate (Bottino et al., 2012). Thus, although synthetic polymers are biodegradable and non-cytotoxic, their rapid degradation may release acidic by-products and cause localized foreign body reactions, characterized by presence of macrophages and intracellular remnants of the polymer, which may cause an immune response (Liu and Kerns, 2014). However, too slow degradation of the synthetic polymer resorbable membranes is not conducive to realizing the GBR program due to the high hydrophobicity (Miroshnichenko et al., 2019). For example, PLA is more hydrophobic than PGA, and degradation time is much longer. In vivo degradation of PLA lasts more than 4 years, but copolymerization with PGA or PCL reduces resorption time to less than 1 year, which is better for GBR (Gentile et al., 2011). One should not confound resorption time and persistence of barrier effect, which is always at least 2 times shorter. Most membranes provide an effective barrier during at least 6 weeks and up to 24 weeks (Wang et al., 2016). In addition, the hydrophilicity and hydrophobicity of the membrane molecules and the wettability of the membrane surface affect the adsorption of extracellular matrix proteins, deposition of platelets, formation of blood clots, and adhesion and morphology of progenitor cells with osteogenic differentiation potential (Hunter and Ma, 2013; Wang et al., 2016). Higher hydrophobicity limits the interaction between polymer and cells, reducing the adhesion of the GBR membrane surface to osteoblasts and fibroblasts and hindering bone tissue regeneration (Hunter and Ma, 2013). The synthesized polymer membranes should have appropriate hydrophobicity and degradation rates to achieve membrane degradation that matches tissue healing. PCL is a semicrystalline hydrophobic biodegradable polyester with good mechanical and degradation properties and tunable microstructure. It is a widely used GBR membrane preparation material in clinical practice (Wissing et al., 2017). As with most synthetic polymers, the high hydrophobicity of PCL results in poor cell adhesion and other behaviors compared to native extracellular matrices (Croll et al., 2004). In order to improve the hydrophilicity of pure PCL membranes, Tais et al. (Costa Salles et al., 2020) modified the hydrophobic surface of PCL membranes using plant extracts Pterodon pubescens Benth (P. pubescens) and Arrabidaea chica Verlot (A. chica). Fibrous membranes associated with plant extracts P. Pubescens, and A. chica showed hydrophilic properties, higher wettability, and zero water contact angles compared with controls. Water contact angle measurement has been shown to provide information about hydrophilicity and hydrophobicity of the membrane surface. The lower the contact angle, the higher the surface hydrophilicity. When the contact angle was lower than 80, osteoblasts’ and fibroblast adhesion was maximum (Shah et al., 2019). Studies have shown that there are free hydroxyls (OH) in the A. chica extract, which leads to its being highly hydrophilic (Aro et al., 2013). When PCL was combined with P. Pubescens, the release of A. chica was increased, which positively affected the adhesion and proliferation of fibroblasts, proving the potential application value of these modified membranes in guiding the regeneration of periodontal bone tissue (Costa Salles et al., 2020). Not only by using plant extracts, hydrophilicity can also be improved by adding bioactive inorganic particles such as hydroxyapatite (HAp), tricalcium phosphate, and bioactive glass (BGs) (Jo et al., 2009; Zhang et al., 2009). Another fast degradable component with good biocompatibility and hydrophilicity can improve the biodegradability and hydrophobicity of the PCL matrix. However, Several synthetic bioresorbable polymers, such as PLA, PCL, and PLGA, have been used to balance resistance and stiffness. The addition of bioactive inorganic particles to these polymers leads to a significant increase in stiffness, and the resultant composites present high elastic module values (Castro et al., 2018; Zhang et al., 2020). The elastic modulus of Jason membrane is 178.9MPa, and its maximum tensile strain (%) is 17.9. In contrast, the Bio-Gide film has an elastic modulus of 15.7 MPa and a maximum tensile strain (%) of 46.8 (Zitzmann et al., 1997). High elastic module values may impair the handling, making their adaptation in different surgical site configurations difficult and may lead to clinical drawbacks like soft tissue dehiscence (Rakhmatia et al., 2013). Therefore, when combining with other hydrophilic substances to modify synthetic polymers, it is necessary to pay attention to the selection of materials and whether the modification destroys the original physical structure and chemical properties of synthetic materials. Studies have found that the polybutylene adipate terephthalate (PBAT), a biodegradable aliphatic-aromatic polyester composed of adipic acid, 1,4-butanediol, and terephthalic acid, is highly flexible compared with conventional synthetic polymers. PBAT allows the incorporation of inorganic particles into its structure without compromising its handling (Jones, 2015; Kashani Rahimi et al., 2017; Wang and Yeung, 2017). Gabriela et al. (Balbinot et al., 2021) successfully prepared a PBAT/BAGNb composite GBR membrane with tailored surface properties and osteogenic induction activity by adding niobium-containing bioactive glasses (BAGNb) to PBAT. The addition of BAGNb moderately strengthened the membrane’s stiffness, reduced the membrane’s water contact angle, and promoted higher interaction between the membrane, blood, and surrounding cells (Verné et al., 2009). Compared with traditional surface modification strategies, coating surface modification can significantly improve cells’ hydrophobicity and adhesion properties. The solid hydrophobic substrates allowed the silk proteins to form a coating of various thicknesses. Previous studies have successfully used recombinant spider silk proteins to coat hydrophobic polymers for biomedical applications and improved their wetting capacity (Harris et al., 2016; Tasiopoulos et al., 2020). The PTFE is a hydrophobic material described by low surface energy and high contact angle (>110°) to water-based compounds. The water contact angle further increases due to the porosity of extended PTFE and can reach up to 160°. Harsh as well as milder surfactants have also been used to improve the wetting and make PTFE substrates more favorable to protein-based solutions. In order to achieve a complete wetting of the porous PTFE membrane, a liquid that intrinsically has a low contact angle (<90°) on the material has to be utilized and then gradually being replaced by water, without introducing entrapped air. The lowest contact angle toward PTFE is reported to be possessed by nonpolar aprotic liquids. This result is because membranes modified with coatings such as natural polymers can better mimic the physiological conditions of the specific cell niche. However, it remains a significant challenge to precisely mimic the physiological state of the particular cell niche in clinical applications (Ejeian et al., 2020). Therefore, some studies use metal-organic framework materials (MOF), which have a wide range of physical and mechanical properties of MOF materials and structural flexibility, as a viable platform for multifactorial control of cell-substrate interaction. And they have achieved good application results (Ejeian et al., 2020). Fatemeh et al. (Ejeian et al., 2020) used the zeolitic imidazolate framework-8 (ZIF-8) commonly used in MOF to crystallize in situ on the polydopamine (PDA) modified membranes, which significantly improved the wettability of the substrate and increased the primary attachment of human dental pulp stem cells (hDPSCs). Previous studies demonstrated the physical properties of the ZIF-8 compact layer. The thickness of this compact layer is about 800 nm, and it has a significant adsorption capacity for silver particles. The polypropylene (PP) membranes modified by PDA/ZIF-8 showed a significant increase in surface hydrophilicity, which can effectively support the growth and proliferation of hDPSCs. In the same way, Julia et al. (Higuchi et al., 2019) used hydroxyapatite nanoparticles (HANPs) coating to modify poly (D, Polymer blends of Poly (D, L-lactic acid) (PDLLA)/PLGA electrospun membranes can effectively improve their hydrophilicity. Moreover, nHA may prevent the diffusion of intermediate degradation products out of the polymer, slowing down the pH drop (Cao et al., 2012). As a result, the acidic autocatalytic degradation of the polymer is slowed down, so that possible inflammation reactions could be avoided or be less severely present, and promoting the membranes to exhibit satisfactory mechanical properties. This study also compares the two methods:sonocoating and electrospraying of nHA suspensions. The results showed that sonocoating was more effective in improving osteocyte adhesion, structural stability, harmful pH changes, and wetting properties and may prolong membranes degradation time, which may be used in the treatment of periodontal bone defects (Higuchi et al., 2019).

In summary, the hydrophilicity/hydrophobicity of synthetic polymer resorbable membranes is of great significance in their preparation and application. Too hydrophilic or hydrophobic polymers may adversely affect the successful implementation of the GBR process since synthetic polymers need to be degraded by hydrolysis. Due to the high hydrophobicity of most synthetic polymers, which leads to poor cell adhesion and other behaviours, recent studies have paid increasing attention to reducing the hydrophobicity of the prepared membranes. In current studies, the degradation and hydrophobicity of synthetic polymer matrix can be effectively improved by copolymerizing a variety of polymers or adding other hydrophilic components. However, it is necessary to pay attention to avoid affecting the excellent mechanical properties and other chemical properties of the synthetic membrane itself when applied with other substances. In addition, many studies have shown that compared with other traditional methods, surface coating modification is a better way to improve the hydrophobicity of composite membranes. However, various methods to enhance the hydrophobicity of synthetic polymer membranes are still not widely used in practice. Therefore, further exploration and comparison are needed in the future to obtain more acceptable preparation or modification methods.

Ideally, GBR membranes require good mechanical properties in combination with space retention and handling capacity. In addition, biological activities should be combined in GBR membranes to promote cell activity and bone repair (Sbricoli et al., 2020). One of the critical factors for the success of GBR is that the membranes have good bone conductivity and osteoinductive properties. They can effectively promote bone growth while avoiding the migration of ectopic osteogenic epithelial cells. Studies have shown that although bone graft materials covered with PLA membrane can form mature bone similar to CM produced, the lack of bone conductivity of PLA membrane hinders its ability to promote bone regeneration, which is not conducive to the realization of GBR (Hwang et al., 2020). Studies have proved that most synthetic polymer materials do not show great biological activity to promote bone formation and lack adequate handling capacity. Therefore, these materials cannot meet the requirements of wide application in different clinical situations and need to be combined with granular bone grafts to enhance the bone bioactivity and bone repair of synthetic polymer membranes (Shankar et al., 2018). HAp is the main inorganic component of enamel, dentin, and bone. Synthetic HAp is widely used as a component of bone and tooth fillers due to its good biocompatibility, bioactivity, and bone conductivity. Adding HAp and other bioactive inorganic particles into the polymers can induce bone conduction properties and accelerate the healing process (Tsai et al., 2019). These bioactive materials can form an apatite-like layer at the interface in vivo by undergoing specific surface reactions, which leads to developing a strong adherent bond with the host hard/soft tissues. The apatite layer stimulates osteoblasts (bone-forming cells) and promotes new bone formation in situ (Hench, 2006). Some studies have shown that Strontium (Sr) is a divalent cation that can partially substitute Ca2+ in the crystal lattice of HAp. Zhang et al. (Shankar et al., 2018) reported that strontium-substituted hydroxyapatite (SrHAp) has a higher solubility than pure HAp due to a difference in ionic radius, which contributes to perturbations in the crystal lattice. Tsai et al. (2018) introduced SrHAp fiber fragments into PCL for the first time to prepare GBR composite membranes. The results proved that PCL-SrHANF composite membranes could produce higher bioactivity and osteogenic potential than PCL membranes alone. The above results may be due to the that the Sr2+ ions released from the PCL–SrHANF membranes enhance the expression and activity of osteogenesis-related genes and proteins through the interaction of calcium-sensing receptor (CaR) with cells to activate inositol-1,4,5-triphosphate production and mitogen-activated protein kinase signaling, which regulate osteogenic differentiation (Caverzasio, 2008). In addition to SrHAp, some studies have shown that octacalcium phosphate (OCP) can also produce better bone induction performance than HAp. OCP can serve as a inductive factor for initiating bone deposition and directing osteoblast differentiation by releasing inorganic phosphate (Pi) ions when hydrolysed (Ishiko-Uzuka et al., 2017; Sai et al., 2018). Wang et al. (2020) introduced OCP into poly (3-hydroxybutyrateco-4-hydroxybutyrate) (P (3HB-Co-4Hb) to formed P (3HB-Co-4Hb)/OCP nanofiber membrane through electrospinning for GBR, which significantly increased the osteogenic activity of P (3HB-Co-4Hb) membrane. Therefore, the introduction of OCP is expected to improve the osteogenic and bone conductivity of synthetic polymers for medical applications. However, with the development of MOF nanostructures, many recent approaches have utilized MOF nanoparticles for improving osteoconductivity/osteoinductivity of standard bone substituents, such as titanium, poly-l-lactic acid, and calcium phosphate (Ejeian et al., 2020). MOF is a porous structure whose favorable nanostructural properties can minimize the requirement for bioactive inducible molecules and provide an alternative to chemical-based cellular microenvironments (Min et al., 2019; Ejeian et al., 2020). Fatemeh et al. (Ejeian et al., 2020) prepared a PP membrane modified by PDA/ZIF-8 coating, which showed superior osteogenic biological activity and could effectively support the growth and proliferation of DPSCs. In addition, it has been reported that adding alginate, gelatin, growth factors, and other active factors can also improve the bone-inducing activity of synthetic polymer membranes (Fuji et al., 2009; Kurobane et al., 2019).

In summary, the low bone conductivity and osteogenic induction properties of synthetic polymer materials limit synthetic polymer resorbable membranes’ effective potential for realizing GBR programs. Researchers often introduce HAp, SrHAp, OCP, and other bioactive inorganic particles to improve these defects, showing superior application potential to improve osteogenic induction activity. In addition to osteogenic cations such as Sr2+, newly developed MOF nanoparticles and different bioactive compounds such as growth factors can also modify the membrane surface to improve its bioactivity. However, using bioactive inorganic particles widely may change other physical properties of the membranes. It is necessary further to explore the study of MOF and bioactive compounds.