3D-Printed Bioceramic Scaffolds for Alveolar Bone Regeneration: A Systematic Review with Engineering Context

2.5. Data Extraction and Analysis

This review evaluated patient-specific 3D-printed calcium-phosphate scaffolds as standalone grafts versus conventional materials for dento-alveolar bone regeneration. Authors, year, aim of the study, methodology, treatment / intervention, and the findings of the study were used as variables variables shown in (Table 1). Data were extracted independently by two reviewers, with discrepancies resolved by discussion; sources and the page/figure numbers were noted for those values for which there was consensus. The provided studies were summarized into three themes: clinical effectiveness of 3D-printed calcium-phosphate scaffolds in dento-alveolar regeneration, precision-fit and workflow feasibility of patient-specific CaP scaffolds, and from CaP sources to CaP-polymer composite, material composition and manufacturing routes. Digital workflow information such as CAD/CAM software, printing and sterilising techniques were also obtained were available.

2.6. Quality Assessment

The included studies were appraised using Joanna Briggs Institute (JBI) for human research and QUIN for in-vitro work (Appendix B). JBI checklist showed that RCT of Kijartorn et al. 2022 [13] and Kim et al. 2024 [12] had true randomisation reported; allocation concealment and blinding were not reported, with consistent outcome measurement and appropriate statistics. Thus, it showed a moderate risk of bias. JBI Case series Mekcha et al. [17] revealed clear inclusion criteria and standardised measurement, reporting an adequate overall small risk. QUIN scores maximum of 24, with Anderson et al. 2022 [18] scoring 14/24, Ghezzi et al. 2024 [19] scoring 14/24, Li et al. 2025 [20] scoring 14/24, Zheng et al. 2025 [21] scoring 13/24; as strengths in specimen preparation, characterisation, and reporting. Common limitations were sample size, specimen randomisation, and blinding. Disagreements were resolved by consensus.

2.7. Ethical Consideration

This work does not involve direct contact with human participants and access to identifiable data; this work is based on studies, from publicly accessible sources and published work, that are used as raw data. Thus, the requirement for institutional ethics approval was not required. The review followed accepted reporting guidelines and practiced methodologically and consistently with citation and fidelity with the original data. Any possible conflicts of interest were documented for the purpose of interpreting the evidence base transparently.

3. RESULTS

The study highlights clinical effectiveness with evidence from human studies. Preclinical and engineering studies are also reported separately as translational context but they are not used to infer clinical efficacy.

3.1. Human Clinical Effectiveness Evidence (Systematic Synthesis)

Empirical data in three-dimensional printed calcium-phosphate (CaP) scaffolds in clinical settings are presently limited to two randomised controlled trials and one prospective case series, all of which have brief follow-up intervals. These papers enable a premature but tentative evaluation of clinical efficacy in Alveolar Ridge Preservation (ARP) and Guided Bone Regeneration (GBR) and highlight strong methodological and interpretive drawbacks.

3.1.1. Study Set, Indications, and Comparability

In the comprised human study, clinical evidence is based on two parallel-arm RCT and one prospective but not comparative case series representing fledgling clinical translation and not comparative effectiveness studies. The evidence is decisively divided in the case of ARP and GBR, whose differences are biological limitations, morph shape defect formation, and guided clinical purposes. The ARP RCT compared a group of post extraction sockets with 4 months interval to heal [13]. The GBR RCT, on the other hand, was done on the bigger horizontal defects, where the evaluation was done at around five to six months [12]. The outcomes in the case series at six months before the placement of the implant were also reported [17]. The difference in interventions was also significant. The nano-porous hydroxyapatite scaffold manufactured by 3D-printing for ARP was compared to a nanocrystalline alloplastic particulate bone graft under coverage of the membrane [13]. Customised 3D printed biphasic CaP blocks (HA: β-TCP 60:40) were tested in GBR, in comparison to conventional non-custom block grafts [12]. The series in the case used patient nano-HA blocks, frequently in combination with biologic adjuvants, including focused growth factors or platelet-rich fibrin [17]. These variations preclude cohort quantification, which enables evaluation of consistency or deviation of signals between indications.

3.1.2. Alveolar Ridge Preservation: Non-inferiority Within a Biological Ceiling

Kijartorn et al. [13] showed 3D-printed nano-porous hydroxyapatite scaffolds provide similar outcomes with 3D-nano crystalline alloplast in terms of radiography, histology, and implant stability, 4 months after transplantation. Changes in CBCT-based horizontal and vertical ridge also showed no significant difference between groups, while histomorphometric analysis showed a similar percentage of new bone and remnant graft material. The values of implant stability at place and initial follow-up were also found to be equal, showing clinically acceptable implant positions regardless of the type of graft. Compared with the Guided Bone Regeneration trial by Kim et al. [12], no observable bone-quality gain in ARP suggests an indication-specific drawback. The process of socket healing is constrained by early bundle bone resorption and vascular remodelling, restricting the capacity of graft material to preserve the size of ridges. Within the biological limit, findings by Kijartorn et al. [13], demonstrate non-inferiority rather than superiority of the intervention evaluated; however, the short follow-up, small sample size, and incomplete reporting of allocation concealment reduces the statistical significance with increase in risk for bias, limiting sensitivity to detect treatment effects.

3.1.3. Guided Bone Regeneration: A Consistent Early Bone-Quality Trend Signal Without Dimensional Superiority

Contrary to ARP, Kim et al. [12] report Guided Bone Regeneration RCT studies revealed statistically significant increase, with a consistent trend towards higher BV/TV in bone volume fraction (BV/TV) and a decrease in tissue surface in defects treated in customised 3D-printed biphasic CaP blocks compared to conventional blocks. These micro- CT observations indicated there was a higher density of the regenerate at around five to six months, but there was no substantial difference in absolute bone volume, surface to volume ratios, bone mineral density, and radiographic ridge sizes across the groups. This deviation, when directly compared to the ARP results of Kijartorn et al. [13], highlights the role of defect environment. GBR defects are larger, open, mechanically stiffened, and tolerant to the variations in bone quality, and ARP sockets are biologically capped. Notably, Kim et al. [12] lacked downstream clinical benefits because no evidence in regard to survival of implants, loss of marginal bone, and patient-reported outcome were studied. Thus, BV/TV increase must be regarded as an early bioindicator and not an indicator of excellent clinical outputs.

3.1.4. Supportive Feasibility Evidence and Contextual Contradictions

Mekcha et al. [17] outline in the prospective case series that patient-specific 3D-printed CaP blocks can be applied clinically, with horizontal ridge gains, volumetric gain, implant stability rate, and histological bone formation, after six months. Nonetheless, the initial graft exposures and later-on protocol adjustments that include biologic supplements complicate the ability to allocate results solely to the scaffold. In contrast to RCTs conducted by Kijartorn et al. [13] and Kim et al. [12], the study does not employ any control group and has confounding variables that do not allow making any causal inferences. Mekcha et al. [17] does not support or deny superiority claims when synthesised with the randomised evidence. Rather, it reinforces practicability and emphasises variability at earlier clinical adoption. The comparison of ARP equivalence [13], GBR bone-quality signal [12], and case-series heterogeneity [17] indicates that whatever benefit there might be in customised printed CaP scaffolds is indicator-specific, but it has yet to be established in controlled trials.

The clinical indications of the synthesised evidence suggest that 3D printed CaP scaffolds indicates biological activity and comparable to conventional grafting materials during the early phases of healing. Current evidence shows these scaffolds show superiority as compared to the present available grafting materials in terms of clinical and radiographic outcomes.

In ARP, the results interact homogeneous among the materials, which is in line with biological limitations. In GBR, there is some slight increase in bone-quality measures without evident dimensional advantage. These are internally consistent but clinically undeveloped signals. All the research are constrained due to small sample size, limited follow-up, disparate outcome measures, and failure to report on randomisation and blinding procedures. The endpoints vary significantly (CBCT compared to micro-CT compared to histology), which does not allow pooling and makes narrative comparison the only possible synthesis. Variability in CBCT protocols, histomorphometric definitions, follow-up periods, and implant-stage assessments substantially limited inter-study comparability. Therefore, the review presents only a narrative synthesis, while the existing evidence base can be seen as a hypothesis-generating, rather than a conclusive one.

3.2. Translational and Preclinical Context (Non-Clinical Evidence)

In addition to the few human experiments, 3D printing of calcium phosphate (CaP) has been studied through translational and preclinical studies on the manufacturability, architectural control, and material behaviour of 3D printed scaffolds. These studies lack clinical efficacy but provide the background information for design, feasibility and probable hypothesis that can be used in the future to optimise the clinical study.

3.2.1. Manufacturing Feasibility and Precision-Fit at Clinical Scale

The uniformity of technical feasibility is observed across the translational research: patient-specific CaP scaffolds can be produced on a clinically relevant scale. Anderson et al. [18] confirmed the feasibility of an end-to-end CBCT-to-print workflow, showcasing that customised CaP constructs could be fabricated with less than-millimetric variations from the planned design (mean 0.27 mm) while maintained neutral pH, ISO-compliant cytocompatibility and compressive behaviour under membranes. These findings overcome the long-standing translational hurdle in block grafting by fabricating patient specific constructs that adapt to the complicated shapes of defects.

Nevertheless, the data can be interpreted as feasibility evidence compared to the existing human trials particularly when compared to the limited data available from the human trials (Kijartorn et al. [13], Kim et al. [12]). Although precision-fit has been technically proven, there is no qualified controlled clinical study that improves the geometric fidelity for enhanced bone regeneration or superiority in implant outcomes. The proposed workflow advantages such as decreased intraoperative trimming or lower risk for graft contamination, have been inferred, and not evaluated by clinical studies. The work of, Anderson et al. [18] advances validation and manufactured feasibility with clinical effectiveness as a secondary option that requires further investigation.

3.2.2. Architecture and Material Studies Defining the Design Space

Material and architecture-oriented research goes further to define the design space of CaP scaffolds by studying the effects of composition, porosity, and fabrication tracks on mechanical behaviour and cellular responses. Zheng et al. [21] proved that it is possible to use tooth-derived CaP to generate scaffolds that have maintained hydroxyapatite phases, predictable shrinkage, and compressive properties in cancellous-bone scales through digital influence of light. The computational and experimental comparisons conducted on the lattice geometries showed that permeability and distribution of stress could differ significantly with architecture, which supports the point of view that internal design affected transport and load sharing. Equally, the works of polymer-ceramic composite by Ghezzi et al. [19] and Li et al. [20] depicted that the increment in ceramic content advances the stiffness, surface roughness and osteogenic indicators in-vitro. Such studies reveal through trade-offs; increased ceramic loading can lead to and enhance brittleness or handling tolerance. Notably, such studies do not give a causal relationship between a given architectural parameter and a patient level outcome. The lack of standardised reporting of architectural outcome data in human trials also restricts clinical translation of findings.

3.2.3. What Translational Evidence Can and Cannot Support

The translational and preclinical literature, when combined, can be used to make two defensible conclusions. Firstly, reproducible production of patient-specific CaP scaffolds with high geometric fidelity, acceptable mechanical behaviour, and cytocompatibility demonstrates technical feasibility in clinical testing (Anderson et al. [18], Zheng et al. [21]). Secondly, these studies produce testable hypotheses, which are plausible and define how scaffold composition and architecture can affect biological behaviour. The information is, however, incapable of bearing claims of clinical superiority, highly successful implantation, or beneficence to the patient. In vitro osteogenic markers, simulated transport measures and mechanical optimisation are not a replacement of controlled human evidence. Clinical outcomes are indication-dependent and multifactorial, as demonstrated by the differences between ARP equivalence (Kijartorn et al. [13]) and GBR a consistent early bone-quality trend (Kim et al. [12]). Translational evidence must be considered as scaffolding, not explanatory until architectural variables have been reported and run-in trials sufficiently powered to use them to explain clinical outcomes.

5. DISCUSSION

The study consists of only two randomised controlled trials and one case series with short follow-up of human evidence available; the rest of the evidence is of an engineering and in-vitro study. Primary and secondary endpoints were not prespecified: workflow-related measures, including trimming time, chairside efficiency, and risk of contamination, were not quantitatively assessed. They are presented as feasibility metrics instead of clinical benefits. In this review, clinical outcomes were prespecified; however, workflow measures were not quantitatively reported in the included trials.

Concerning the preservation of the alveolar ridge, the available evidence shows no examples of inferiority. 3D-printed calcium-phosphate scaffolds produce ridge dimensional maintenance and histological outcomes that are similar to modern alloplasts through the initial healing phase. The null outcome of ARP randomised controlled trial conforms to a biologically limited model wherein socket resorption is early and predictable. Graft materials have a predominant impact on the quality of the fills and not the alleviation of buccal plate remodelling. Here, an optimised printed calcium-phosphate scaffold can mimic the behaviour of state-of-the-art particulate alloplasts, though it would take a purposive adjustment of internal architecture to achieve biomimic socket biology. The ARP physiological remodelling ceiling is biologically constrained. Therefore, the 3D-printed calcium-phosphate scaffolds appear non-inferior to current alloplasts, providing similar dimensional and histological preservation and histological outcomes at early stages, which is a satisfactory outcome.

For Guided Bone Regeneration (GBR), the evidence suggests a small bone-quality signal for customised 3D-printed CaP blocks (e.g., higher BV/TV), while linear ridge gains appear broadly comparable at early follow-up. The GBR signal above converges with engineering-to-clinic feasibility work showing that patient-specific CaP blocks can be produced with sub-millimetric accuracy. Anderson et al. [18] report a complete digital workflow from CBCT segmentation to print, with printed OsteoInk™ scaffolds. It demonstrated ~0.27 mm mean morphological deviation from the design and maintained neutral culture pH with ISO-compliant cytocompatibility features that plausibly reduce intra-operative trimming, dead-space, and early exposure risk. The review findings indicate the advantages of a fit-driven workflow, with feasibility and biocompatibility of 3-D printed CaP scafolds supporting the trend for improved early bone-quality across the included study trend aligned with Anderson et al. [18], with CBCT-to-print scaffolds that minimize trimming and dead space. Mechanically, OsteoInk™ achieved higher compressive strength than a hybrid CaP formulation, reinforcing its space-maintenance role under membranes. The platform’s feasibility is consistent with the BV/TV findings by Kim et al. [12] supporting potential clinical applications. It states that if a scaffold truly “fits-and-fixes” the defect, it can prioritise biology (perfusion, stable clot, guided osteogenesis) over chairside turning, helping bone fraction even when linear width gains seem similar to controls.

Besides the works by Kim et al. [12] and Anderson et al. [18], the broader scope of the evidence used provides an additional background. The evidence in the ARP randomised controlled trial [11] supports non-inferiority of 3D printed calcium-phosphate scaffolds in the initial healing phases, but the case series [17] focuses on feasibility alone, with a learning curve in soft-tissue early complications and resulting adjustment of protocols. The in-vitro and production studies demonstrated that phase composition, sintering settings, composite formulation, and lattice structure can significantly impact mechanical characteristics and cellular reactions. This highlights that the term ‘3D -printed CaP’ is not a monolithic intervention [20, 21].

Mechanically, it is possible but not proven directly by experimentation on which this review rests, that sub-millimetric adaptation and internal architecture tune clot stability, perfusion dynamics, and early osteogenic processes in humans. It is plausible that precision-fit scaffolds may reduce micromotion and handling requirements; however, these workflow-related mechanisms were not quantitatively assessed in the clinical trials. It is an economic and biological burden that customisation can mitigate. Architectural choices then govern what happens inside the block. This explains why BV/TV can increase without dramatic linear gain if transport and marrow ingress are optimised locally [12]. Materials then set the boundary conditions, where Anderson et al. [18] document stable pH and better cytocompatibility for a sintered CaP paste (OsteoInk™) relative to a hybrid CaP, supporting a “bio-friendly” microenvironment for early cells. Mechanistically, it is plausible that precision-fit, internal porosity, and stable CaP phases interacting synergistically; however, this hypothesis has not yet been validated in controlled human trials.

Superiority claims likely require functionally graded porosity tailored to buccal plate biology and vascular supply rather than simply swapping material labels. For GBR, where defects are larger, and space maintenance is decisive, the combination of precision-fit blocks and supportive internal architecture plausibly confers incremental benefits. Although the BV/TV difference appears statistically small, its clinical relevance depends on whether it reflects a denser, more mature regenerate at the planned implant placement stage. Clinically, even small increases in regenerate density at implant placement may reduce perceived need for secondary augmentation or improve drilling stability, although this remains unproven in long-term studies. Micro-CT readouts higher showing higher BV/TV with reduced tissue surface represent improvements in bon regeneration that are associated with early implant stability [12]. However, between groups, the outcomes were similar and fewer cases required second-stage augmentation even with similar CBCT widths. In both indications, consistent ISQ/IST at re-entry is clinically reassuring, but harmonised timepoints and landmarks are needed to make placement-stage decisions comparable across trials.

Two orthogonal axes, envelope sufficiency and bone fraction/quality, should be interpreted together. CBCT width/height determines whether implants can be placed with ≥2 mm buccal bone, while BV/TV, % of new bone, and residual graft informs long-term remodelling and stability. Our corpus demonstrates that bone fraction can shift upwards even when linear dimensions are unchanged. This should be interpreted as added value from geometry/architecture (customisation) rather than contradiction. Micro-CT or histology becomes co-primary with CBCT in printed-block trials, with exposure/membrane complications reported uniformly.

Heterogeneity across indication (ARP vs GBR), endpoints (CBCT vs micro-CT vs histology), and time (~4 vs ~5–6 months) makes pooling fragile. Differences in CBCT acquisition parameters, landmark selection, and histomorphometric processing further reduce direct comparability between studies. A pragmatic core outcome set would include CBCT- based ridge measuring width at fixed levels (e.g., 1, 3 and 5 mm apical to the crest) using standardised vertical landmarks, along with a bone-quality panel (BV/TV, percentage of new bone, percentage of residual graft) assessed by histology or micro-CT. Implant stability (ISQ/IST) at placement and re-entry, and complication rates reported with uniform definitions and assessment windows must also be included. Trials must pre-register membrane type, adjuncts, and fixation, and report groups, means, Standard Deviation, and exact timepoints to enable meta-analysis. Standardised reporting of CAD/CAM software, printing parameters, scaffold post-processing, and sterilisation workflows is also necessary to improve reproducibility across centres. The limitations of follow-up limit generalisation on volumetric stability after remodelling, exposure of membranes with time, and maintaining early differences on bone-quality. Outcome measurement heterogeneity (e.g., different CBCT landmarking protocols, micro-CT panel definitions, and histological processing) makes inter-study comparison unreliable and meta-analytic pooling inappropriate, reducing clinical guidance accuracy.

Strengths of Anderson et al. [18] include a full CBCT (CAD/CAM) print pipeline demonstrated at a clinical scale, with rigorous materials characterisation (neutral pH, ISO-compliant cytocompatibility) and mechanical testing showing superior compressive behaviour versus a hybrid CaP. Crucially, fit accuracy is quantified (≈0.27 mm mean morphological deviation) and sub-millimetric bone-graft gaps are mapped, consistent with reduced trimming and contamination risk. The paper incorporates transparent and reproducible methods, that offers a realistic surgical benchmark, for practical quality assurance that translates neatly into clinical workflows and future RCT standardisation [21].

Material choices shape what reaches the clinic. Tooth-derived CaP slurries for DLP offers circular supply chain and high-resolution lattices. Zheng et al. [21] formalised a CAD-to-DLP workflow to optimise dispersion, solids loading and sintering parameters to demonstrate in-vitro apatite formation, supporting manufacturability and surface reactivity. The study also highlights uncertainties related to process control and batch consistency that are necessary regulators for scrutiny. Polymer-ceramic filaments for FFF/FDM could unlock on-demand patient-specific prints with improved handling. The study by Li et al. [20] showed that PLA reinforced with HA/β-TCP (7:3) raises compressive strength and boosts ALP/mineralisation in vitro, as a promising carrier while preserving CaP bioactivity, yet clinical benefit remains hypothetical without human data. Mapping these to our RCT identified differences in phase composition, sintering and lattice design plausibly to BV/TV parity, underscoring the need to disclose microstructural specs in clinical reports.

In terms of future aspects, future trials shall use grade versus uniform soils within the outer geometry of each patient, with the endpoint of 5-6 months with stratification as ARP/GBR. Plan non-inferiority on envelope (CBCT) and superiority on BV/TV; control membrane type, adjuncts (e.g., PRF/CGF), flap design, and fixation to isolate scaffold effects. Core is safety and PROs – exposure, pain and return to function. Economically, track OR, time, dispose rates, revisit rates and delayed implant costs. Clinically, the current evidence supports non-inferiority in ARP at early healing, while GBR shows a small bone-quality signal that requires confirmation in larger, longer, standardised trials for ARP when anatomy or workflow favours customisation. In GBR, customised printed CaP suggests a possible signal of better bone fraction and a cleaner workflow, especially when internal architecture is designed for transport, and the CaP phase is well-sintered and cytocompatible.