Biological approaches and biomaterial-based solutions for bone reconstruction: A comprehensive review

Table 1 Horizontal comparison of the main categories of bone graft materials

Ref.	Type of graft	Main properties	Advantages	Limitations	Typical clinical applications
[142,143]	Autograft	Osteogenic, osteoinductive, osteoconductive; no immune response	Gold standard; high predictability; rapid integration	Donor-site morbidity; limited volume	Large defects, non-unions, orthopedic reconstruction, maxillofacial surgery
[144,145]	Allograft	Mainly osteoconductive; may retain osteoinductive potential depending on processing	No second surgical site; wide availability	Possible immune reaction; slower integration; disease transmission risk	Orthopedic revision surgery, spinal fusion, large defects
[146,147]	Xenograft	Highly osteoconductive; stable porous structure; slow resorption	Excellent volume maintenance; good scaffold for bone growth	Very slow remodeling; no osteogenic potential	Alveolar ridge preservation, sinus lift, moderate orthopedic defects
[148,149]	Synthetic (HA, β-TCP, bioceramics)	Controlled porosity; adjustable resorption; bioinert or bioactive depending on composition	No risk of disease transmission; unlimited availability; tunable properties	Lower mechanical strength; variable integration depending on formulation	Filling small to medium defects, orthopedic revisions, periodontal/trauma defects
[150,151]	Composite biomaterials	Combine organic and inorganic components; mechanical reinforcement; enhanced bioactivity	Balanced resorption; improved handling; increased mechanical stability	Higher cost; variable performance depending on formulation	Load-bearing defects, trauma reconstruction, implant dentistry

HA: Hydroxyapatite; β-TCP: Beta-tricalcium phosphate.

Table 2 Classification of bone substitute biomaterials according to information provided by the manufacturers: Biomaterials of natural origin

Ref.	Commercial name/country/company	Composition	Physical properties	Biological properties	Mechanical properties	Resorption/integration	Clinical efficacy	Form/cost
[167]	Bonefill Porous®/Brazil/Bionnovation	Mineralized bovine spongy xenograft	White granules, irregular, porous	Biocompatible, osteoconductive, high interconnectivity	Lightweight, strong; maintains space and support	Slow and progressive (6-9 months)	Documented use in sinus lift, GBR, and alveolar filling	Granules (0.10-2.5 mm)/affordable
[168]	Cerabone®/Germany/Botiss	100% inorganic, calcined bovine bone	Purified ceramic; hard and stable particles	Biocompatible; osteoconductive; bone scaffold	High stability and strength	Very slow; progressive integration	Well-established use in peri-implant grafts, sinus lift, and bone augmentation	Granules and blocks (0.5-4 mm) high
[169]	Geistlich Bio-Oss®/Switzerland/Geistlich	Bovine xenograft	Porous, similar to human bone	Biocompatible, osteoconductive	Preserves volume and structure	Slow, promotes maintenance	Widely used in implant dentistry; proven clinical efficacy	Granules and blocks (0.25-2 mm) high
[172]	GenMix®/Brazil/Baumer	Inorganic bovine xenograft (cortical and cancellous matrix)	Dry granules, lightweight; high volumetric stability; good handling	Biocompatible; osteoconductive; promotes new bone formation; no transmission risk	Good initial strength; intermediate support	Slow and partial (some particles > 12 months); integration 6-9 months	Used in alveolar grafts, sinus lift, ridge augmentation; studies show predictability and maintenance	Granules (0.25 mm; 0.5 mm; 1.0 mm)/affordable cost
[195]	GenOx Inorg®/Brazil/Baumer	Inorganic bovine xenograft (mineral bone matrix, sintered)	Rigid, stable granules; resistant to rapid resorption; volume-maintaining	Biocompatible; osteoconductive; non-immunogenic; slow bone replacement	High initial strength; prolonged support; indicated for load-bearing areas	Very slow (> 24 months)	Used in sinus lifts, ridge augmentation, alveolar filling, and periodontal applications; proven efficacy	Granules (0.25 mm; 0.5 mm; 1.0 mm; 2.0 mm)/affordable cost
[170]	GenOx Org®/Brazil/Baumer	Organic and inorganic bovine matrix (type I collagen)	Lightweight, porous, and moldable; trabecular structure	Biocompatible, osteoconductive, potential osteopromotive effect	Lower resistance; suitable for low-load areas	6 months to 12 months	Effective in GBR, fillings, and esthetic areas; good remodeling	Granules (0.25-2 mm)/affordable
[173]	Lumina-Bone Porous®/Brazil/Critéria	Inorganic lyophilized bovine xenograft	Highly porous, bone-like	Biocompatible, osteoconductive	Preserves volume and structure	Slow (6-12 months or more)	Successful in reconstructions, sinus lift, and preservation	Granules (0.25-1 mm)/affordable
[174]	MinerOss XP®/United States/BioHorizons	Porcine xenograft (inorganic bone matrix)	Dry, sterile, irregular granules; high volumetric stability	Biocompatible; osteoconductive; good bone integration	Limited structural support; dimensional stability	Slow (6-9 months)	Widely used in GBR, sinus lift, alveolar preservation, and peri-implant defects; good volumetric maintenance and integration	Granules (0.25 mm; 1.0 mm; 2.0 mm)/high cost
[196]	OrthoGen Granules®/Brazil/Baumer	Bovine xenograft	Rigid granules; good volumetric stability; non-collapsing	Biocompatible; osteoconductive; guides bone growth; no rejection	Adequate structural support; maintains space; compatible with membranes/PRF	Very slow (up to 24 months)	Used in GBR, ridge augmentation, sinus lift, peri-implant, and post-extraction; studies show stability and osseointegration	Granules (0.25 mm; 0.5 mm; 1.0 mm; 2.0 mm)/affordable cost
[197]	OsteoBiol Apatos®/Italy/Tecnoss	Porcine or equine xenograft	Dry, rigid, trabecular granules	Biocompatible; osteoconductive; matrix for osteoprogenitor cells and new bone formation	High temporary resistance; good support and volume maintenance	Slow (9-12 months)	Effective for sinus lift, alveolar regeneration, and ridge augmentation; extensive clinical and histological evidence	Granules (0.25-2.0 mm)/moderate to high cost
[175]	OsteoBiol Gen-Os®/Italy/Tecnoss	Porcine or equine xenograft (cortical and cancellous bone + preserved collagen)	Natural trabecular structure; easy handling	Biocompatible; osteoconductive; native collagen promotes regeneration	Temporary structural support; maintains volume	Slow (6-12 months)	High efficacy; supported by multiple clinical and histological studies	Granules (0.25 mm; 1.0 mm; 2.0 mm)/intermediate cost
[176]	Osteosynt®/Brazil/EincoBio	Bovine xenograft (HA + β-TCP)	Dry, white granules; texture similar to cancellous bone; high volumetric stability	Biocompatible; osteoconductive; no inflammatory response; supports cell colonization and bone formation	Non-deformable; maintains space; limited mechanical load support	Slow (6-18 months)	Used in GBR, sinus lift, post-extraction sockets, and peri-implant defects; maintains volume; can be combined with membranes or PRF	Granules (0.25 mm; 1.0 mm; 2.0 mm), block, wedge, sphere/affordable cost
[177]	SmartBone®/Switzerland-Italy/IBI	Bovine xenograft (HA) + biodegradable polymers + type I collagen	Rigid trabecular structure	Biocompatible; osteoconductive; bioactive; rapid tissue integration	High compressive strength; excellent stability; can be fixed with plates or screws	Slow (6-18 months)	Recommended for load-bearing reconstructions in implantology, orthopedics, and oncology; extensive scientific documentation	Granules, blocks, and strips/high cost
[178]	THE Graf®/South Korea/Purgo	Porcine bone mineral matrix, similar to human bone	Interconnected pores, high hydrophilicity	Biocompatible, free of immunogenic agents, osteoconductive	Stable structure for regeneration	From 10 weeks	In vitro, in vivo and clinical studies	Granules/high

HA: Hydroxyapatite; β-TCP: Beta-tricalcium phosphate; PRF: Platelet-rich fibrin; GBR: Guided bone regeneration.

Table 3 Classification of bone substitute biomaterials according to information provided by the manufacturers: Synthetic and composite biomaterials

Ref.	Commercial name/country/company	Composition	Physical properties	Biological properties	Mechanical properties	Resorption/integration	Clinical efficacy	Form/cost
[179]	Alobone poros®/Brazil/Osseocon	Synthetic: Low-crystallinity hydroxyapatite	Porous granules, promote vascularization	Biocompatible, osteoconductive, protein-free	Suitable for filling bone defects	Gradual, replaced by new bone	Positive results in sinus lift, ridge augmentation, and preservation	Granules (0.25-1 mm)/affordable
[180,181]	BioGran®/United States/Zimmer Biomet	Alloplastic; bioactive glass 45S5 (calcium sodium silicate)	Translucent white; microporous; high surface area	Biocompatible; osteoconductive; potentially osteoinductive; stimulates osteogenesis, angiogenesis, and HA formation	Stable in small to moderate defects; no structural support in load-bearing areas	Rapid (3-6 months); efficient	Good results in alveolar, peri-implant, periodontal, and sinus regeneration	Granules (0.3-0.35 mm)/moderate to high
[182]	Bonecerami®/Switzerland/Straumann	Alloplastic; 60% HA + 40% β-TCP	3D structure similar to cancellous bone	Biocompatible; osteoconductive; cell adhesion; no significant inflammatory response	Lightweight and stable; not indicated for high-load areas without protection	4-6 months; β-TCP resorbs first; HA maintains volume	High predictability in GBR, sinus lift, and alveolar filling; comparable to xenografts	Granules (0.5/1.0-2.0 mm)/moderate to high
[181]	Calcigen S®/United States/Zimmer Biomet	Alloplastic; calcium sulfate	Moldable (spheres, blocks, wedges); powder-liquid mix; sets in 4-6 minutes	Biocompatible; osteoconductive; promotes bone growth	Quick application; not indicated for load-bearing support	8-12 weeks	Used as filler in orthopedics and dentistry; conducive environment for bone regeneration	Powder for mixing/moderate to high
[171]	GenPhos HA TCP®/Brazil/Baumer	Synthetic: 70% HA + 30% β-TCP	Porous granules, similar to cancellous bone	Biocompatible, osteoconductive, protein-free	Good initial strength, lower than ceramics	Slow (7-9 months); gradual integration	Positive use in sockets, ridge augmentation, and peri-implant areas	Granules (0.5-0.75 mm)/affordable
[183]	Grafton DBM®/United States/Medtronic	Allogeneic; demineralized human bone + glycerol	Moldable; ready to use; adapts to irregular defects	Biocompatible; osteoconductive and potentially osteoinductive; stimulates osteogenesis and angiogenesis; forms HA in situ	Limited support; not indicated for load-bearing areas	3 months to 12 months (variable)	Widely used in reconstructions, implants, and orthopedics	Gel, paste, sponge, strip/high cost
[184]	HAP-91®/Brazil/JHS Biomaterials	Synthetic; pure synthetic HA	White, homogeneous granules; high volumetric stability; non-collapsing	Biocompatible; osteoconductive; non-immunogenic; promotes bone conduction	Good initial strength; adequate support for load and non-load areas; non-moldable	Very slow (18-24 months)	Indicated for alveolar grafts, sinus lift, GBR, peri-implant, and ridge augmentation; volumetric maintenance and osseointegration	Granules (0.15 mm; 0.3 mm; 0.5 mm; 1.0 mm; 2.0 mm)/affordable cost
[185]	MinerOss®/United States/BioHorizons	Allogeneic; human cortical and/or cancellous bone	Dry and rehydratable particles; easy adaptation	Biocompatible; osteoconductive; possible residual osteoinduction	Intermediate support	4 months to 9 months (variable)	Widely used in implant dentistry and GBR	0.25 mm to 1.0 mm; particulate (cortical, cancellous, or mix)/moderate to high cost
[186]	Nanosynt®/Brazil/National OsteoBiotec	Synthetic: 60% hydroxyapatite + 40% β-TCP	Porous nanostructure, high capillarity	Biocompatible, osteoconductive, non-immunogenic	Good initial stability; intermediate mechanics	Controlled/moderate; β-TCP resorbs in 4-6 months; HA persists	Good outcomes in preservation, bone augmentation, and peri-implant procedures; systematic reviews	Granules (0.25-2 mm)/affordable
[187]	OsteoGen®/United States/Intra-Lock	Alloplastic; synthetic HA	Dry, lightweight granules; maintains stability	Biocompatible; osteoconductive; non-immunogenic	Fragile; moderate support in cavities	6-9 months	Used in implants, post-extraction sockets, and periodontics; good but limited literature compared to others	Granules (0.3-0.5 mm), dry/Lyophilized; strips/Low to intermediate cost
[188]	Vitoss®/United States/Stryker Corp	Synthetic β-tricalcium phosphate (β-TCP)	Lightweight, porous, hydrophilic texture; easy to handle	Biocompatible; osteoconductive; stimulates vital bone formation	Fragile structure; compressible and adaptable but requires stabilization; not recommended for load-bearing sites	Moderate (4-9 months)	Effective in small to medium defects; indicated for trauma, spine, orthopedics, implantology, and periodontics	Granules and moldable putty/moderate to high cost

HA: Hydroxyapatite; β-TCP: Beta-tricalcium phosphate; GBR: Guided bone regeneration.