Table 1.

The summary of periodontal biomaterials.

Biomaterials	Characteristics	Performances		Advantages	Limitations	Refs.
		In Vitro	In Vivo
Bioactive agents	Biological or synthetic agents with both antibacterial and osteogenic effect	Antibacterial effect on Porphyromonas gingivalis (P. gingivalis) and Streptococcus mutans (S. mutans) Promotion of osteogenic differentiation of human periodontal ligament fibroblasts (hPDLFCs) and human periodontal ligament cells (hPDLCs)	Reduction in bone loss in animal model Probing depth (PD) reduction, clinical attachment level (CAL) gain and percentage of radiographic defect depth reduction (DDR%) in a clinical trial	Safety, abundant sources	Unknown active ingredient and mechanism	[8,11,14,15,49]
Guided tissue regeneration/guided bone regeneration (GTR/GBR) membranes	Composite membranes based on natural or synthetic polymers, combined with antibacterial and osteogenic components They act as cell barriers to prevent the invasion of epithelium and connective tissues, facilitating alveolar bone regeneration	Antibacterial effect on P. gingivalis, S. mutans, Fusobacterium nucleatum (F. nucleatum), Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), Streptococcus sanguis, Micrococcus luteus, Salmonella typhimurium, Peptostreptococcus anaerobius (Pa), Actinobacillus actinomycetes (Aa) and Enterococcus faecalis (E. faecalis) Promotion of mineralization, proliferation, osteogenic differentiation of osteoblasts, fibroblasts, hPDLCs, bone marrow mesenchymal stem cells (BMSCs), Mg63 cells, MC3T3 cells, human periodontal ligament fibroblasts (HPDLFs), mesenchymal stem cells (MSCs), human periodontal ligament stem cells (hPDLSCs) and dental pulp stem cells (DPSCs) Induction of M2 phenotype polarization of macrophages	Reduction in bone loss, promotion of mucosal healing, new bone formation and fibril matrix deposition in animal model CAL gain, radiographic defect bone level (DBL) gain, reduction in PD and gingival recession (GR) in a clinical trial	Good biocompatibility, better mechanical property compared with traditional membrane, controllable biodegradability, drug encapsulation and release ability, manageability as well as accurate matching with the defects	Long degradation time, unknown long-term metabolic effect and toxicity of elements	[9,17,18,20,21,22,23,24,25,26,27,28,29,30,31,34,35,36,37,38,40,41,42]
Tissue engineering scaffolds	Scaffolds are composed of natural or synthetic polymers, antibacterial components, proteins or cells They are grafted to bone defect to maintain space, store growth factors, support cell attachment and proliferation	Antibacterial effect on F. nucleatum, P. gingivalis, S. aureus and Aggregatibacter actinomycetemcomitans (A.actinomycetemcomitans) Promotion of osteogenic differentiation of hPDLCs, hPDLSCs, promotion of osteogenic and odontogenic differentiation of human periapical cyst mesenchymal stem cells (hPCy-MSCs) and promotion of preosteogenic responses of MC3T3-E1 cells	Promotion of cementoid tissue formation in animal model	Good mechanical property, loading and sustained release of active ingredients, antibacterial property, improved osteoinduction and osteogenesis performances	Potential toxicity of certain ingredient, lack of research on osteogenic ability in vivo	[39,46,47,48]
Drug delivery systems	Natural or synthetic polymers are loaded with antibacterial and osteogenic components Along with systems’ degradation, active components experience burst release followed by sustained release	Antibacterial effect on A. atinomycetemcomitans, Prevotella nigricans (P. nigrescens), E. coli, S. aureus, P. gingivalis, E. faecalis, S. mutans and Streptococcus sanguinis (S. sanguinis) Promotion of proliferation, migration, attachment and osteogenic differentiation of human bone marrow-derived osteoblasts (HOB), BMSCs, osteoblasts and PDLSCs, promotion of mineralization	Reduction in bone loss, increase in new bone formation and improvement of gingival index in animal model	Stability, stimulus responsiveness, effective controlled release mode, long-lasting effects	Potential toxicity of certain ingredients	[11,13,50,51,52,53,54]