Open research questions in Bone Tissue Engineering Materials

What the literature leaves open

• Investigate new self-assembling biomaterials for minimally invasive therapies. Explore additive manufacturing methods to enhance spatial control over scaffold geometry and composition. Study the integration of electrospun scaffolds with biological functions for enhanced differentiation.

  Editorial: Biomimetic scaffold materials for engineering of in-vitro tissue/organ models and in-vivo tissue repair · 2026 · DOI

• The gap lies in the integration of advanced scaffold fabrication techniques to improve both in vitro and in vivo applications. There is a need for more sophisticated control over scaffold structure and function to better mimic native tissues.

  Editorial: Biomimetic scaffold materials for engineering of in-vitro tissue/organ models and in-vivo tissue repair · 2026 · DOI

• The use of nanoparticles in denture base materials raises concerns regarding their potential toxicity and biocompatibility. The incorporation of alpha-silver tungstate into denture base resin is a novel approach to enhance its antimicrobial activity.

  Characterization, antimicrobial activity, biocompatibility, and inflammatory response of 3D-printed denture base resin functionalized with alpha-silver tungstate · 2026 · DOI

• the study used a rat model, - the extraoral time was limited to 15 min to preserve PDL cell viability, - the study did not evaluate the long-term effects of the repair materials

  Periodontal tissue responses following vertical root fracture repair with 4-META/MMA-TBB resin mixed with nano-hydroxyapatite · 2026 · DOI

• further studies are needed to evaluate the long-term effects of the repair materials, - the effects of naHAp/SB on human periodontal tissue should be investigated, - the optimal concentration of naHAp in SB should be determined

  Periodontal tissue responses following vertical root fracture repair with 4-META/MMA-TBB resin mixed with nano-hydroxyapatite · 2026 · DOI

• Limited availability of autologous bone block, - Donor-site pain and morbidity, - Unpredictable resorption rate of autologous bone block, - The need for a second surgery for autologous bone block, - Limited sample size of 4 Beagle dogs

  Osteoinductively Functionalized 3D ‐Printed Scaffold for Vertical Bone Augmentation in Beagle Dogs · 2024 · DOI

• Further studies are needed to investigate the long-term effects of BMP2-inc. BpNcCaP/HA-func. 3D scaffolds, - Research on the optimization of the scaffold design and material properties, - Investigation of the potential applications of BMP2-inc. BpNcCaP/HA-func. 3D scaffolds in other fields of tissue engineering

  Osteoinductively Functionalized 3D ‐Printed Scaffold for Vertical Bone Augmentation in Beagle Dogs · 2024 · DOI

• The identity and function of titanium-adhesive blood proteins are unclear. The role of biomolecules in osseointegration is not well understood. The effect of titanium-adhesive proteins on cell adhesion and bone formation is unknown.

  Titanium-adhesive vitronectin promotes peri-implant bone formation via cell adhesion acceleration: An experimental study · 2026 · DOI

• PURPOSE: Osseointegration begins at the initial blood-implant contact; however, titanium-adhesive blood proteins remain incompletely defined.

  Titanium-adhesive vitronectin promotes peri-implant bone formation via cell adhesion acceleration: An experimental study · 2026 · DOI

• However, it remains unclear whether extensive remodeling of such coatings is compatible with high osseointegration in vivo.

  Ultra-thin porous calcium phosphate coatings show extensive remodeling and high osseointegration after 24 weeks in a rabbit femoral condyle model · 2026 · DOI

• However, the early molecular mechanisms through which it directs mesenchymal stem cell (MSC) behavior remain poorly understood.

  Brushite-modified titanium surface elicits early osteointegrative gene expression signatures in human mesenchymal stem cells: insights from NGS analysis · 2026 · DOI

• However, their protective performance under high-velocity impact is lacking investigation.

  Gradient double-twisted Bouligand structural design for high impact resistance over a wide range of loading velocities · 2025 · DOI

• Bone regeneration requires coordinated anabolic and catabolic signaling, yet the interplay between mammalian target of rapamycin complex 1 (mTORC1) and adenosine monophosphate-activated protein kinase (AMPK) pathways remains unclear.

  Metabotissugenic citrate biomaterials orchestrate bone regeneration via citrate-mediated signaling pathways · 2025 · DOI

• Non-collagenous proteins (NCPs) play a crucial role in directing intrafibrillar collagen mineralization during hard tissue formation, however, their functions and control mechanisms remain elusive and controversial.

  Tuning the Intrafibrillar Collagen Mineralization Rate and Mechanical Properties Through Polyelectrolyte‐Controlled Formation and Crystallization of Amorphous Precursor · 2025 · DOI

• Although the surface topography of implant materials influences both osteogenesis and inflammatory responses, its effects on pyroptosis and osteogenesis under inflammatory conditions have not been thoroughly investigated.

  Micro-/nano-structured zirconia surface promotes osteogenic differentiation of human bone marrow mesenchymal stem cells by reducing pyroptosis under inflammatory conditions · 2025 · DOI

• This study focuses on the bone regenerative potential of three-dimensional (3D) nanofiber-based polyglycolic acid (nPGA), whose capacity for bone regeneration remains unclear.

  The utility of 3D nanostructured polyglycolic acid fibers for novel bone regenerative medicine · 2025 · DOI

• Although bone grafting remains a primary clinical approach, its efficacy is limited by these adverse conditions.

  Zinc Oxide-Copper Sulfide Nanozyme Hydrogels for Bone Defect Repair by Modulating the Bone Immune Microenvironment and Promoting Osteogenesis/Angiogenesis · 2025 · DOI

• faecalis, whereas further research on AgCu/80S glasses is necessary to optimize ion release conditions, assess bioactivities, and explore potential dental applications.

  Antimicrobial properties of bimetallic-containing mesoporous bioglass against Enterococcus faecalis · 2024 · DOI

• Increasingly studies have reported that nanomaterials (NMs) can induce and regulate the biomimetic mineralization of dental hard tissue, but few studies have examined how they are involved in the different stages, let alone the relevant mechanisms of action.

  Unraveling Nanomaterials in Biomimetic Mineralization of Dental Hard Tissue: Focusing on Advantages, Mechanisms, and Prospects · 2024 · DOI

• Existing methods are limited by a lack of safety, efficiency, short-lasting anti-infective ability, and inadequate consideration of the immunomodulatory effects on osteogenesis.

  “Photo-Thermo-Electric” Dental Implant for Anti-Infection and Enhanced Osteoimmunomodulation · 2024 · DOI

• Nonetheless, the application of such scaffolds in bone tissue engineering has been limited by the lack of a scaffold that can simultaneously provide both the intricate electromechanical environment and the biocompatibility of the native bone tissue.

  Piezoelectrically and Topographically Engineered Scaffolds for Accelerating Bone Regeneration · 2024 · DOI

• However, limited literature is available regarding bionic zirconia implants using the TPMS structure for bone regeneration.

  3D Printed Porous Zirconia Biomaterials based on Triply Periodic Minimal Surfaces Promote Osseointegration In Vitro by Regulating Osteoimmunomodulation and Osteo/Angiogenesis · 2024 · DOI

• However, their application in periodontal tissue regeneration has been scarcely explored.

  ECM-Mimicking Strontium-Doped Nanofibrous Microspheres for Periodontal Tissue Regeneration in Osteoporosis · 2024 · DOI

• In ovariectomized rabbit osteoporotic femurs, HCG monotherapy forms new bone with less osteocyte damage (fewer empty bone lacunae) and fewer osteoclasts than osteoporotic bone; however, it is insufficient to prevent receptor activator of nuclear factor-kappa B ligand (RANKL) overexpression.

  Carbonate Apatite Honeycomb Scaffold-Based Drug Delivery System for Repairing Osteoporotic Bone Defects · 2024 · DOI

• However, it remains unknown whether and how FPHA affects the immune microenvironment of the bone defects.

  Fluorinated hydroxyapatite conditions a favorable osteo-immune microenvironment via triggering metabolic shift from glycolysis to oxidative phosphorylation · 2024 · DOI

Most-cited papers in Bone Tissue Engineering Materials

• Bioceramics: From Concept to Clinic · Journal of the American Ceramic Society · 1991 · 4,327 citations
• Self-Assembly and Mineralization of Peptide-Amphiphile Nanofibers · Science · 2001 · 3,506 citations
• Bioceramics · Journal of the American Ceramic Society · 1998 · 2,603 citations
• Third-Generation Biomedical Materials · Science · 2002 · 2,436 citations
• Surface treatments of titanium dental implants for rapid osseointegration · Dental Materials · 2006 · 2,035 citations
• Calcium orthophosphates in medicine: from ceramics to calcium phosphate cements · Injury · 2000 · 813 citations
• Guided bone regeneration: materials and biological mechanisms revisited · European Journal Of Oral Sciences · 2017 · 727 citations
• Spontaneous Formation of Bonelike Apatite Layer on Chemically Treated Titanium Metals · Journal of the American Ceramic Society · 1996 · 636 citations
• Surface characteristics of dental implants: A review · Dental Materials · 2017 · 515 citations
• Bone grafts: which is the ideal biomaterial? · Journal Of Clinical Periodontology · 2019 · 500 citations

Most recent work

• Next-generation craniomaxillofacial implants for reconstructive surgery: balancing biomechanics, biocompatibility, and bioactivity · International Journal of Oral Science · 2026
• Poly-l-lactic acid electrospun membrane with specific morphology promotes bone regeneration through macrophage reprogramming · Journal of Nanobiotechnology · 2026
• Early-stage stability and degradation of patient-specific biodegradable 3D-printed implants for critical mandibular reconstruction · Dental Materials · 2026
• Bioactive ZnP-coated 3Y-TZP ceramics for dental implants: Strong interfacial bonding, antibacterial activity, and osteogenic potential · Dental Materials · 2026
• Black phosphorus-based photothermal-responsive hydrogel enhanced osteoporotic bone injury regeneration by alleviating oxidative stress and remodeling bone homeostasis · Journal of Nanobiotechnology · 2026
• Glucose oxidase-mineralized scaffolds with multiple bioactivities for accelerated diabetic bone regeneration · Journal of Nanobiotechnology · 2026
• Hierarchical laminin–MgCO 3 gradient layers on Sr/ZnO ion-implanted titanium for multifunctional bone regeneration · Artificial Cells, Nanomedicine, and Biotechnology · 2026
• In-situ synthesis of angiogenic and osteogenic chitosan-whitlockite composite bone filler · Materials Chemistry and Physics · 2026
• Novel advances and approaches in hydroxyapatite-based coating on metallic biomaterials · Journal of Alloys and Compounds Communications · 2026
• High-resolution fabrication of amorphous calcium phosphate-reinforced polycaprolactone composite scaffolds for bone tissue engineering · Biomaterials Advances · 2026

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