3.1.2. Bioactive Glass and Silicon Dioxide

The form and application of glass have developed along with the development of human civilization for thousands of years [62]. Since the late 1960s, various combinations of bioactive glasses for regenerative medicine have been developed and improved [62]. Due to the bonding ability of bioactive glasses to both hard and soft tissues, and osteoconductive, osteoinductive, and angiogenesis properties, the material is considered a third-generation biomedical material [62–65]. Numerous pieces of research on the bioactive glass coating on dental implants and membranes are ongoing to enhance bone regeneration and induce fast tissue bonding [2,27,66,67]. Furthermore, for improved physical, functional, and chemical properties, the bioactive glasses are incorporated with different ions (e.g., Sr, Cu, Zn, etc.), osteo-induced drugs (bisphosphonate and dexamethasone), and nanoHA [2,15,21,25,26,68].

In 2018, Chen et al. reported a nanometer-sized bioactive glass Ca2ZnSi2O7-coated collagen membrane via a pulsed laser deposition coating technique [2]. This study showed that the expression of osteogenic factors was upregulated and osteogenic differentiation of bone marrow stem cells was enhanced in the coated membrane group, attributable to coated nutrient bioactive glass [2]. In 2020, Dau et al. reported SiO2-enhanced nanoHAcoated collagen membranes via the spin–spray coating method [15]. In this study, SiO2 enhanced nanoHA-coated collagen membranes showed the fastest and most pronounced vascularization properties [15]. In 2019, Terzopoulou et al. reported ibandronate-loaded bioactive glasses-coated poly(ε-caprolactone) (PCL) membrane [25]. In the reported study, two different synthesized mesoporous bioactive glasses (SiO2-CaO-P2O5 and SiO2-SrO-P2O5) were loaded with ibandronate and coated on PCL membranes by the spin coating technique. Both the bioactive glasses demonstrated an increase in hydrophilicity and bioactivity, especially in the ibandronate-loaded and Sr-substituted bioactive glass-coated membranes [25].

#### 3.1.3. Polydopamine and Polydopamine Platform with Other Substances

PDA has been known as one of the most efficient universal surface-coating materials due to its ability to strongly attach to almost all kinds of substrates, since its first report in 2007 [69,70]. PDA has been reported to promote cellular adhesion and mineral deposition of hydroxyapatite [29,71,72]. In addition, PDA is a good platform for surface tethering and releasing small molecules for tailoring the functionality of PDA. The target molecules (polymers, proteins, peptides, and drugs) could be readily immobilized on PDA by ad-layer formation or one-pot coating technique [73–75].

In 2019, Hasani-Sadrabadi et al. developed biomimetic PDA-coated PCL membranes via the membrane immersion technique using dopamine hydrochloride to promote adhesion [29]. In this study, the coated PDA layer was identified to accelerate the osteogenic differentiation of MSCs by promoting hydroxyapatite mineralization [29]. In 2019, Chen et al. reported that the PDA-coated PLLA membrane improved hydrophilicity, cytocompatibility, tensile properties, and osteogenic activity [12], and the membrane was soaked in

1.5 times stimulated body fluid for the biomineralization of HA. In this in vitro study, HA immobilization and PDA coating played a synergistic osteoconductive effect [12]. In 2020, Ejeian et al. reported in situ crystallization of zeolitic imidazolate framework-8 (ZIF-8) on the PDA-modified polypropylene (PP) membrane [33]. The ZIF-8/PDA/PP membrane showed significantly increased osteogenic differentiation of dental pulp stem cells, as well as increased physical properties. In 2022, Lee et al. reported that lactoferrin immobilized the PLLA/PCL membrane by using the polydopamine coating technique [28]. Lactoferrin is known to exhibit biological functional activities such as bone regeneration and antiinflammation [28,76,77]. In this study, the lactoferrin–polydopamine-coated PLLA/PCL membrane showed enhanced osteoinductive and anti-inflammatory activities compared to only the PDL-coated membrane [28].

3.1.4. Drugs for Osteogenesis: Bisphosphonate with or without Testosterone and Dexamethasone

As anti-osteoporotic drugs, the bisphosphonates (e.g., alendronate, ibandronate, and zoledronate, etc.) interfere with the bone turnover process through inactivation of the osteoclast activity, thereby resulting in reduced bone breakdown [1,34]. The bisphosphonates prevent osteoporotic pathologic fractures and improved bone regeneration [34,78]. However, it could also be a causative agent for medication-related osteonecrosis of the jaw [1]. Testosterone is another important osteoanabolic agent in men, that stimulates the proliferation of preosteoblasts and the differentiation of osteoblasts [79]. Currently, bisphosphonate and testosterone combination therapy has been exploited for the synergistic stimulation of bone regeneration [34,35]. As a synthetic glucocorticoid, locally delivered dexamethasone (Dex) showed great osteogenic induction of MSCs [76]. However, the inappropriate systemic delivery of glucocorticoids may cause side effects such as hyperglycemia, immunosuppression, and osteoporosis [76,80].

In 2020, van Oirschot et al., and in 2021, van den Ven et al., reported a testosterone and alendronate ultrasonic spray-coated collagen membrane by using PLGA 5004A as a carrier [34,35]. The drug-coated membranes showed superior bone regeneration to the control group with 124% in the minipig bone defect model and 160% in the rat criticalsize calvarial defect model [34,35]. In 2019, Lian et al. reported dexamethasone-loaded mesoporous silica nanoparticle-coated PLGA and gelatin composite membranes [26]. In this in vitro experiment, the coated membrane showed an enhanced osteoinductive capacity for rat bone marrow stem cells (BMSCs).

#### 3.1.5. Chitosan

Chitosan derived from the deacetylation of chitin derivatives is one of the most important natural polymers and has been reported to induce osteogenesis and enhanced tissue healing [11,81]. It has biocompatible, self-resorbable, antimicrobial, and economical properties [11]. Though it has poor mechanical properties and a low degradation rate, chitosan plays a role in improving the biological, physical, mechanical, and antimicrobial properties of the membranes either alone or in combination with other functional coating materials [36,37,43,49]. Guo et al. reported a chitosan-coated magnesium (Mg) membrane [37]. In this study, chitosan was used to reduce the degradation rate of the Mg membrane and enhance osteogenic activity. The results showed that the chitosan-coated Mg membrane had a suitable degradation rate and a higher osteogenic potential [37]. However, mechanical properties may not be maintained once degradation begins. In 2021, Porrelli et al. reported that silver nanoparticles (nAgs) stabilized a bioactive lactose-modified chitosan-coated PCL membrane [36]. The nAgs lactose-modified chitosan-coated membrane showed enhanced hydrophilic properties, improved osteoblastic adhesion, proliferation, and discouraged biofilm formation without cytotoxicity [36].

#### 3.1.6. Platelet-Rich Fibrin, Enamel Matrix Derivatives, and Amelotin

PRF, as one of the forms of platelet concentrates, is obtained from the autologous venous blood in the glass-coated tube after centrifugation at 400 g. The PRF contains platelets and their byproducts released during platelet activation. These include numerous growth factors, circulating cytokines, glycoproteins, and fibrin-associated glycan chains that are crucial factors for tissue regeneration [82]. In 2020, Kapa et al. reported the clinical study about the treatment with PRF-coated bones and PRF-coated collagen membranes in sixteen patients with gingival recession due to the loss of alveolar bone and soft gingival tissue [38]. In the study, twelve out of the sixteen patients achieved complete healing of gingival recession, and an increase in gingival thickness was observed in all patients [38].

Like PRF, the extract of porcine embryonic enamel matrix termed 'EMD' has been reported to induce mesenchymal cells to mimic the processes of the development of the tooth and has been broadly used for periodontal regenerative treatment [83]. In 2017, Miron et al. reported the EMD in a liquid carrier system coated with a collagen membrane [9]. The EMD-coated collagen membrane showed increased cell adhesion, osteodifferentiation, and mineralization in an in vitro study.

AMTN, an enamel protein expressed by ameloblasts, is known to play an important role in enamel mineralization [84,85]. Furthermore, the AMTN is known to promote HA mineralization [86]. In 2022, Ikeda et al. reported a collagen hydrogel incorporated with rhAMTN (rhAMTN gel)-coated collagen or polyglactin-woven mesh membranes [39]. The AMTN gel-coated membranes showed accelerated mineralization and adhesion.
