Electrospun bone repair and oral barrier membranes: materials, structures, and research progress

01What problems do bone repair scaffolds and oral barrier membranes aim to solve, respectively?

The basic design task of a guided bone regeneration (GBR) membrane is to preserve regenerative space at the target site while restricting the entry of unwanted soft tissue. In contrast, a bone defect scaffold may need to allow cells and blood vessels to enter internally. During R&D, “supporting cell growth” and “blocking cell passage” should not be conflated as a single performance objective. Instead, one should first clarify where the electrospun layer will be placed and which tissue it will contact.^1,2

The oral environment also involves specific issues such as exposure, microbial contact, and fixation methods. A material’s ability to promote osteoblast proliferation in vitro does not mean it has been proven suitable as a periodontal barrier; results from animal calvarial or femoral defects must also be interpreted separately from their application in the actual oral cavity.^1,2,3,4,5,6

02What material and structural combinations does electrospinning provide?

Polycaprolactone (PCL), polylactic acid (PLA or PLLA), PLGA, and polyglycolic acid (PGA) can serve as components of different fibrous systems; gelatin, silk fibroin, and calcium phosphate materials are used to modify the cell-contact interface, wet-state behavior, or mineral composition. The rationale for selecting these components is to combine processability with the desired biological behavior, rather than to determine the final application directly from the material names.^1,2,3,4,5,6

Blend spinning is suitable for comparing single-layer composite formulations; sequential deposition can produce stratified membranes with different surfaces; coaxial spinning can assign support, degradation, or delivery functions to the core and shell layers. Electrospun membranes can also be combined with 3D printed scaffolds, in which the coarser scaffold provides spatial support while the fibrous layer regulates the local interface.^1,2,5,6

03Oral barrier membranes: moving from a single surface toward stratified design

Separately arranging the bone-facing and soft-tissue-facing sides

In 2011, Bottino, Thomas, and Janowski reported a functionally graded membrane prepared by sequential electrospinning: the middle portion consisted of PLCL and a protein/polymer composite layer, while nanohydroxyapatite and metronidazole were introduced on the two sides, respectively. The paper focused on the morphology, structure, and mechanical performance of each layer, demonstrating the feasibility of separately designing the bone-contact and epithelial-contact surfaces. It provides a basis for material-structure research but cannot be used to claim that periodontal tissue has already been regenerated.¹

Enabling fibrous membranes to work synergistically with three-dimensional supports

In 2021, Liu et al. combined heparin-modified PCL/ gelatin electrospun membranes with a PCL/ gelatin/nanohydroxyapatite printed scaffold. Cellular evaluations were conducted separately on the upper membrane and lower porous scaffold, and animal experiments observed bone formation. This shows that the electrospun layer need not bear the entire load-bearing function alone; it can also serve as part of a composite scaffold.²

Although this paper used GBR as the design background, the actual implantation validation employed a distal rabbit femoral defect rather than a patient’s alveolar bone defect. The new bone observed at 20 weeks supports exploration of this composite system for bone repair but cannot be directly rewritten as an oral clinical outcome. For corporate R&D, the next step should be to transfer the structure to the intended site and reevaluate fixation, spatial maintenance, and tissue response.²

04Mineral-composite fibers: the focus is not merely on how much inorganic particulate is added

In 2024, Meng et al. introduced amorphous calcium phosphate (ACP) into PLLA fibers and subsequently constructed a hierarchical pore structure through post-treatment, exposing some polymer-encapsulated particles to the fiber surface. The study also examined wetting, mechanical properties, and cellular responses, observing improved adhesion and proliferation in human osteoblast-like cell cultures over 7 days.³

This work reminds us that, even when calcium phosphate is present in both cases, whether particles are embedded inside the fibers or exposed to the cell-contact surface may produce different interfacial behaviors. Therefore, when comparing composite formulations, dispersion state, surface exposure, and pore structure should be recorded together. This paper presents material and in vitro research and does not thereby prove that bone defects have been repaired.³

It also shows that post-treatment can serve as an R&D variable: electrospinning determines the initial scaffold, while post-treatment further modifies the surface and pore structure. However, identical sampling and evaluation methods should be used before and after treatment, and the structure, wet-state performance, and residues should be checked against the intended application, rather than relying solely on a comparison of post-treated micrographs.³

05Local delivery and core-shell fibers: how to allocate functions around the bone repair process

Different fibers undertake different release functions

In 2023, Al-Baadani et al. combined gelatin fibers containing P substances with PCL fibers containing simvastatin through co-electrospinning. The study linked different release processes to cell recruitment, vascular-related responses, and osteogenesis, evaluating migration, endothelial networks, and osteogenic indicators in vitro and observing bone formation in a rat calvarial defect. This is a research example of “division of labor between two types of fibers within a single membrane,” not a clinical recommendation for any drug formulation.⁴

Using core-shell differences to regulate wet-state support and degradation

In 2024, Zhang et al. prepared a coaxial fibrous scaffold using a PGA core and a silk fibroin shell. The study focused on wet-state toughness, staged degradation, and osteogenic response, and validated new bone formation in a rat calvarial defect. Here, the value of the core-shell structure is not limited to drug loading: it can also be used to coordinate the structural maintenance and degradation processes of two materials in bodily fluids.⁵

Simultaneously observing osteogenic and osteoclastic-related responses

In 2024, Anjum et al. loaded alendronate sodium into a PCL core layer, introduced hydroxyapatite into a PLGA shell layer, and applied a polydopamine surface modification. The study examined both osteogenic and osteoclastic-related behaviors in vitro, followed by observation in a rat calvarial defect for up to 12 weeks. It expanded the evaluation from a single osteogenic indicator to the coordination of bone formation and resorption, but it remains an animal study of a specific system.⁶

06Reading bone repair literature: how to distinguish results at different levels

Cell adhesion and proliferation address whether cells can survive and expand on the material; alkaline phosphatase, osteogenic gene expression, and mineralization staining further provide differentiation-related information; animal microCT and histology are used to observe new bone formation within defects. The former layer of evidence is valuable but cannot directly replace the latter, much less independently demonstrate clinical osseointegration or long-term load-bearing capacity.^2,3,4,5,6

It is also important to ensure consistency in controls and intended use. A porous bone scaffold that attracts cells may not necessarily be suitable for directly serving as an oral barrier to block soft tissue. Skull, femur, and alveolar bone models are also not entirely identical. The literature selected in this review does not provide human efficacy trials; thus, it is more appropriate for clarifying material strategies and validation pathways, rather than making clinical judgments about all electrospun bone repair materials.^1,2,3,4,5,6

07From literature to reproducible bone repair membrane samples

When preparing samples, first describe the sample morphology: a planar barrier membrane, a thin coating that can be wrapped, or a three-dimensional composite scaffold requiring a certain thickness. Subsequently, specify the material system, effective dimensions, thickness or surface density, pore structure, and wet-state handling requirements. This provides a clear sample target for liquid supply, nozzle, collection, and post-processing configurations.

For fibers containing mineral particles, attention should be paid to dispersion, sedimentation, and compositional changes after prolonged liquid supply; for core-shell or bilayer systems, record the liquid supply routes, deposition sequence, and interlayer bonding. After increasing the area, comparable sampling positions should be selected at the center and edges of the membrane, as well as in the early and late stages of preparation. Process stability must be supported by sample testing and cannot be inferred solely from the ability to continuously produce fibers.

Product validation also requires consideration, depending on the specific application, of residual solvents, post-sterilization structure, biocompatibility, degradation, and necessary fixation and spatial retention performance. Equipment handles preparation and process control, whereas material suitability depends on corresponding testing and research.^1,2,5

08Common issues in bone repair and oral barrier membrane R&D

Can ordinary PCL fiber membranes be directly used as GBR membranes?

PCL can serve as a research starting point, but the membrane’s barrier function, wet-state structure, and spatial retention must still be validated. After adding gelatin, minerals, or drugs, overall performance should also be reevaluated; suitability cannot be judged solely based on a single material name.^1,2,4

Does adding hydroxyapatite prove osteogenesis?

No. The presence of particles, cell-related osteogenic responses, and new bone formation in animals represent different types of evidence. It should be specified which layer the particles are in, how they contact cells, and which evaluations were actually conducted.^1,3,6

Equipment configuration should first address whether to use coaxial or multiple nozzles

First describe the structure to be achieved. If internal compartmentalization within a single fiber is required, coaxial electrospinning can be discussed; if two types of fibers coexist or different layers have distinct functions, multiple liquid supply routes, co-deposition, or sequential deposition should be discussed. The final configuration must be determined based on the solution system and sample validation.^1,4,5,6

References

The following are the original studies used in this review, independently summarized by TONGLI. The interpretation of the literature does not imply that the paper authors or research institutions have equipment procurement or cooperative relationships with TONGLI; the specific reading scope is described in each literature entry.

Bibliographic records retain the original publication language for accurate lookup.

1. Bottino MC, Thomas V, Janowski GM. A novel spatially designed and functionally graded electrospun membrane for periodontal regeneration. Acta Biomaterialia. 2011;7:216–224.

   DOI：10.1016/j.actbio.2010.08.019 ↗

   Reading scope: original journal abstracts and bibliographic information; animal or human effects are not inferred from this

2. Liu J, Zou Q, Wang C, et al. Electrospinning and 3D printed hybrid bi-layer scaffold for guided bone regeneration. Materials & Design. 2021;210:110047.

   DOI：10.1016/j.matdes.2021.110047 ↗

   Reading scope: local original full text; focus on reviewing the animal models and results in the 2.6 section

3. Meng C, Liu X, Li J. Hierarchical porous PLLA/ACP fibrous membrane towards bone tissue scaffold. Journal of the Mechanical Behavior of Biomedical Materials. 2024;152:106455.

   DOI：10.1016/j.jmbbm.2024.106455 ↗

   Reading scope: local original full text, with verification of the authors’ institutional paper records

4. Al-Baadani MA, Xu L, Cai K, et al. Preparation of co-electrospinning membrane loaded with simvastatin and substance P to accelerate bone regeneration by promoting cell homing, angiogenesis and osteogenesis. Materials Today Bio. 2023;21:100692.

   DOI：10.1016/j.mtbio.2023.100692 ↗

   Reading scope: local original full text and the full text of PMC

5. Zhang Y, Jian Y, Jiang X, et al. Stepwise degradable PGA-SF core-shell electrospinning scaffold with superior tenacity in wetting regime for promoting bone regeneration. Materials Today Bio. 2024;26:101023.

   DOI：10.1016/j.mtbio.2024.101023 ↗

   Reading scope: local original full text, with verification of the bibliographic information in PubMed

6. Anjum S, Wang Y, Xin Y, et al. Bioinspired core-shell nanofiber drug-delivery system modulates osteogenic and osteoclast activity for bone tissue regeneration. Materials Today Bio. 2024;26:101088.

   DOI：10.1016/j.mtbio.2024.101088 ↗

   Reading scope: local original full text and the full text of PMC