Unilateral biportal endoscopy for minimally invasive spinal fusion: Advancements in biomaterials and clinical outcome optimization

Abstract

Lumbar interbody fusion is essential for treating degenerative lumbar diseases. The disadvantages of open surgery have led to the evolution of minimally invasive spine surgery, including endoscopic techniques such as unilateral biportal endoscopy (UBE). Leveraging arthroscopic principles, UBE offers superior visualization and flexibility and expands from decompression to fusion (UBE fusion). However, achieving robust UBE fusion presents challenges, such as suboptimal arthrodesis rates and implant-related complications, requiring more than surgical skill alone. Optimizing UBE fusion critically depends on the effective integration of advanced biomaterials with the surgical technique. This minireview assessed recent advances in UBE, focusing on the development of novel biomaterials, such as functionalized porous, expandable, or double-cage designs, to improve bone regeneration outcomes. These advancements address challenges, like washout of bone graft material and biologics, and utilize growth factors, such as recombinant human bone morphogenetic proteins, while exploring pathway modulation to improve outcomes. We also evaluated clinical optimization strategies involving technical refinements, fluid and hemostasis control, key complication mitigation especially concerning dural tears and hematomas, and technologies such as navigation and robotics. While UBE shows promise particularly for early recovery, its long-term success hinges on these biotechnological advancements. High-quality evidence, especially from randomized controlled trials and long-term studies, is needed to validate integrated strategies and define the optimal role of UBE fusion.

Key Words: Unilateral biportal endoscopy; Unilateral biportal endoscopy fusion; Biomaterials; Interbody cage; Bone healing; Clinical outcome

Core Tip: Unilateral biportal endoscopic fusion is a promising minimally invasive technique to treat lumbar degenerative diseases. Achieving optimal long-term outcomes necessitates intelligently integrating advanced biomaterials, such as novel cages (e.g., expandable, double), optimizing grafts, refining surgical techniques, and effectively managing complications (e.g., dural tear, hematoma). This minireview highlighted recent advances in biotechnological integration for optimizing clinical results. Future directions should focus on smart materials and navigation and robotics technologies. There is a critical need for high-quality evidence, particularly randomized controlled trials, to validate these integrated strategies and define the role of unilateral biportal endoscopic fusion.

INTRODUCTION

Lumbar interbody fusion (LIF) is an essential surgical treatment option for various degenerative lumbar diseases causing low back pain and neurological dysfunction in the lumbar spine[1]. However, traditional open surgery has several disadvantages including soft tissue trauma and prolonged recovery. Therefore, the continuous development of minimally invasive approaches in spinal surgery has been undertaken to reduce surgical trauma, accelerate patient recovery, and improve long-term outcomes[2]. Minimally invasive spine surgery (MISS) has shifted from tubular retractor-based methods, such as minimally invasive transforaminal LIF, to more precise endoscopic techniques. Although minimally invasive transforaminal LIF reduces muscle stripping, the limitations of tubular retractors hinder deep operative field visualization and the ability to manage complex anatomy[3]. Against this backdrop unilateral biportal endoscopy (UBE) has emerged as a novel MISS technique.

Leveraging arthroscopic principles, UBE utilizes two separate portals (one for independent viewing and one for working) within a fluid medium, offers superior visualization, and enhances surgical flexibility[4]. Following successful application in lumbar decompression[5], the UBE technique has rapidly expanded to spinal fusion procedures (UBE fusion) (Figure 1)[6]. There are several key technical advantages: (1) High-definition endoscopic visualization, which facilitates precise neural decompression and thorough cartilaginous endplate preparation[7]; and (2) Dual-portal separation, which allows instrument triangulation and operative freedom approaching open surgery, enabling effective discectomy, bone grafting, and cage placement[8].

Figure 1 Unilateral biportal endoscopic decompression and key anatomical corridors utilized in unilateral biportal endoscopic fusion. FLA: Ligamentum flavum; Lt: Left.

However, like other endoscopic interbody fusion techniques, UBE fusion has several challenges including the potential for insufficient bone graft volume, suboptimal fusion rates, graft or cage subsidence, hardware loosening, and pseudarthrosis formation[9]. These challenges compromise long-term outcomes and may necessitate revision surgery. Consequently, improving arthrodesis rates following endoscopic LIF is a critical focus for clinical investigation[10]. Achieving optimal clinical outcomes depends critically on the UBE technique itself as well as the effective integration of advanced biomaterials (novel interbody cages and bone healing strategies) with the surgical approach[11,12].

This minireview systematically reviewed recent key advances in UBE fusion, with the goal of providing a valuable reference for clinical practice and future research. Its core focus was two-fold: (1) Elucidate how novel biomaterials (e.g., functionalized cages, optimized bone graft materials) can be organically integrated with the UBE technique to promote interbody fusion and enhance clinical outcomes; and (2) Assess associated clinical outcome optimization strategies.

INTEGRATING BIOMATERIALS IN UBE FUSION: FROM STRUCTURAL SUPPORT TO BIOLOGICAL ENHANCEMENT

The success of UBE fusion surgery depends on meticulous decompression and stabilization as well as the optimized integration of interbody implants and bone grafting strategies. They are crucial for achieving long-term solid fusion and maintaining spinal alignment. Interbody cages are the primary structural support and have evolved beyond simple mechanical fillers to incorporate biological activity. Table 1 provides a comparative overview of commonly used interbody cage options, highlighting differences in materials such as polyetheretherketone (PEEK) and titanium alloys, as well as advancements like porous/three-dimensional (3D)-printed structures, PEEK-titanium composites, expandable designs, and the double-cage strategy.

Table 1 Comparison of common interbody cage options for spinal fusion.

Cage type	Material	Osseointegration	Elasticity	Radiolucency	Subsidence risk (theoretical)
Standard PEEK cage	PEEK	Inert	Bone-like	Excellent	Low
Porous titanium/three-dimensional-printed titanium cage	Titanium alloy	Excellent	Higher	Fair/poor	Moderate
PEEK-titanium composite cage	PEEK, titanium	Moderate/good	Variable	Good	Low/moderate
Expandable cage	Titanium, PEEK, or both	Variable	Variable	Variable	Variable
Double-cage construct	PEEK, PEEK-titanium composite	Moderate/good	Variable	Good	Potentially low

PEEK: Polyetheretherketone.

Traditional materials such as PEEK are widely used due to their bone-like properties of elasticity and excellent radiolucency, aiding in subsidence prevention[13]. However, PEEK exhibits relative inertness regarding osseointegration[14]. By contrast, titanium alloys and their derivatives, especially newer cages with surface modifications (e.g., roughening, plasma-sprayed hydroxyapatite coating) or porous designs (e.g., porous titanium, 3D-printed biomimetic porous titanium/tantalum), significantly enhance bone ingrowth, promoting biological fusion[15]. Nonetheless, their higher stiffness might theoretically increase subsidence risk[16].

The UBE technique offers a unique perspective for applying these advanced materials. Its superior visualization allows surgeons to precisely assess cage placement and endplate contact. This precision is particularly vital when positioning porous metal cages to optimize osseointegration[17]. Simultaneously, surgeons selecting cages for UBE must also consider the radiographic properties and intraoperative endoscopic visibility of the material. For example, certain radiopaque titanium cages require specific designs or reliance on intraoperative imaging, including direct endoscopic visualization of markers, to confirm accurate positioning[18].

Concurrently, interbody cage structural design must adapt to the constraints of minimally invasive channels, like those used in UBE, while enhancing biomechanical performance and fusion potential. The advent of expandable cages addresses the challenge of inserting larger volume or appropriately lordotic cages that are necessary for restoring disc height and segmental lordosis through small access portals. Theoretically, direct visualization via UBE can facilitate monitoring the cage expansion process within the disc space, ensuring safe and effective correction[19].

Furthermore, large footprint strategies have been designed to counteract the potential issues of smaller interbody cages including insufficient stability and an increased subsidence risk. Successful application of the double-cage technique under UBE has been reported; this technique involves placing two smaller cages (e.g., PEEK and PEEK-titanium composite) side-by-side within the same disc space[20], significantly increasing the cage-endplate contact area. Preliminary studies indicated acceptable early fusion outcomes and a very low rate of significant cage subsidence with this technique. Additionally, cage surface modifications enhance bone healing potential.

Custom designs tailored for UBE workflows (e.g., incorporating navigation markers, optimizing inserter interfaces, antimigration features) along with innovations in bone grafting instruments collectively contribute to improved fusion outcomes[21]. Given that cage subsidence is a focal concern in all LIF procedures, UBE, with its capacity for meticulous endplate preparation under direct endoscopic vision, may potentially mitigate iatrogenic subsidence risk by better preserving endplate integrity. However, this hypothesis requires confirmation through high-quality comparative studies[22].

Beyond the structural support provided by the cage, optimizing bone grafting and bone healing strategies are central to achieving biological integration and long-term fusion success. Autograft, often harvested locally from removed lamina or facet joints, remains the “gold standard” for bone grafting due to the combination of osteogenic, osteoinductive, and osteoconductive properties. However, limitations in the quantity of autografts available and potential donor site morbidity necessitate alternative grafting agents. Consequently, allografts, demineralized bone matrix, and various synthetic bone graft substitutes (e.g., calcium phosphate ceramics, bioactive glass, calcium sulfate) are widely employed for UBE fusion[23].

The unique continuous fluid irrigation environment inherent to UBE presents a significant challenge for graft washout. Therefore, clinical practice favors graft materials or formulations with enhanced cohesiveness, moldability, and irrigation resistance. For instance, osteoinductive putties, viscous bone cement, and strip-based grafts maintain their integrity in a fluid environment and are preferred over loose particulate grafts. Specialized bone graft delivery devices, such as cannulas with precise applicators or bone graft funnels with plungers, are often required for effective packing and targeted containment within the disc space in this setting, minimizing dispersion during delivery through the irrigation stream. Furthermore, intraoperative techniques, such as temporarily reducing irrigation flow during critical moments of graft placement if visualization permits and safety is ensured and meticulous layering and gentle impaction of the graft material under direct endoscopic vision, can also contribute to better graft retention.

The application of bioactive factors offers a potent means to accelerate bone healing. Recombinant human bone morphogenetic proteins (BMPs) are noted for their strong osteoinductive capacity. However, their use requires careful consideration due to significant complications including ectopic bone formation, postoperative edema/seroma, radiculitis, and even tumorigenicity. Within the relatively confined and continuously irrigated UBE surgical field, BMP concentration control, effective containment, and potential side effects from high local concentrations require particularly rigorous evaluation[24]. High-quality clinical evidence on the safety and efficacy of recombinant human BMPs within UBE fusion is lacking. If their use is considered for UBE fusion, then strict adherence to approved indications and dosages must be followed. Other biologics, such as the synthetic peptide-based anorganic bovine-derived hydroxyapatite matrix/cell binding peptide, show promising fusion-promoting potential and may offer safer alternatives to UBE fusion[25].

The efficacy of all biomaterials and enhancement strategies relies on an understanding of the biological basis of bone healing. Comprehending the underlying molecular mechanisms is crucial for guiding future biomaterial design and application. Recent basic research has illuminated the complex interplay or crosstalk between the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and Wnt/β-catenin signaling pathways. These pathways regulate osteoblast function (proliferation, differentiation, mineralization) and bone regeneration, which are processes central to spinal fusion. This understanding leads to new avenues for biomaterial development. Future interbody cages or bone graft systems may evolve beyond inert fillers into “intelligent” biological platforms. These platforms could actively and precisely modulate key bone healing signaling pathways through surface functionalization or internal drug loading[26]. This approach induces and accelerates bone fusion at the molecular level, thereby transitioning from structural reconstruction to true biological function restoration. This biointegrative strategy likely represents a core direction for optimizing the long-term clinical efficacy of UBE fusion.

OPTIMIZING CLINICAL OUTCOMES IN UBE FUSION

An advantage of UBE is its high-definition, magnified visualization allowing surgeons to perform precise neural decompression and thorough cartilaginous endplate curettage under direct vision while maximally preserving bony endplate integrity. These steps are paramount for promoting fusion and enhancing neurological recovery[27]. However, accessing the full visual advantage requires efficient fluid management and meticulous hemostasis strategies. Maintaining continuous clear irrigation is fundamental for UBE but requires precise infusion pressure control to avoid obscuring bleeding points or causing pressure-related complications. UBE fusion typically requires prolonged operative time, which has limited its widespread application. Therefore, optimizing workflow, standardizing surgical steps, and enhancing team collaboration are crucial for reducing the operative time and improving overall efficiency[28].

Computer navigation systems have considerable potential. Enabling real-time tracking of instruments and implants via navigation can significantly improve the accuracy of cage and pedicle screw placement, reduce intraoperative radiation exposure, and potentially accelerate the surgeon’s learning curve by shortening critical operative steps and providing intuitive guidance. Augmented reality and artificial intelligence may offer further support in surgical planning, risk prediction, and real-time decision-making. Overlaying virtual information (e.g., preoperative plans, anatomical structures) onto the surgical field for UBE procedures may enhance precision and safety and reduce invasiveness, ultimately giving patients who receive spinal fusion better outcomes[29].

MANAGEMENT OF UBE FUSION-RELATED COMPLICATIONS

Dural tears are the most frequently reported complication in UBE-related surgeries, with an approximate incidence of 4.5%. Risk factors include surgeon experience, surgical field adhesions, and ligamentum flavum calcification[30]. Preventive strategies involve meticulous anatomical dissection and operating only when excellent visualization is obtained. Small dural defects can often be managed conservatively if a tear occurs. Alternatively, UBE allows for direct endoscopic repair using agents such as fibrin glue or specialized suturing techniques[31]. Although symptomatic postoperative epidural hematoma is rare (1.1%), it can have severe consequences. Because the hydrostatic pressure in the UBE environment might temporarily mask minor active bleeding, meticulous intraoperative hemostasis is imperative. This includes thorough inspection after reducing irrigation pressure before closure[32].

Appropriate placement and management of surgical drains are also crucial for preventing hematoma formation[33]. Nerve root irritation, injury, and transient palsy (overall incidence of 2.6%) result from excessive intraoperative traction, inadvertent radiofrequency energy injury, or prolonged high fluid pressure. Intraoperative neuromonitoring and gentle handling of neural structures mitigate these risks. Incomplete decompression and recurrence highlight the importance of thorough intraoperative exploration to ensure adequate decompression. The inherent flexibility of UBE, such as the use of angled instruments and contralateral exploration, facilitates this goal[34]. Furthermore, surgeons must carefully manage water dynamics to prevent complications. Precise control of infusion pressure and flow rates is necessary to avoid rare but serious events like increased intracranial pressure or water intoxication.

CONCLUSION

UBE has successfully been applied to LIF and is a promising MISS option due to advantages in reducing perioperative trauma and accelerating early recovery. The superior visualization and operative flexibility inherent to UBE, particularly for precise neural decompression and thorough endplate preparation, establish a foundation for enhanced quality of the fusion. However, overcoming the remaining challenges of UBE fusion, including potential limitations in bone graft volume, suboptimal fusion rates, cage-related complications, and specific fluid-medium risks (e.g., graft washout, dural tears, epidural hematomas), requires more than surgical skill advancement alone. This minireview emphasized that the long-term success and optimization of clinical outcomes in UBE fusion depend on the intelligent integration of advanced biomaterials (including bioactive cages and bone grafting strategies adapted for the aquatic environment) with the surgical technique.

Optimizing cage biomechanics and osseointegration via 3D printing, expandable technology, double-cage strategies, cautiously applying osteoinductive factors (e.g., BMPs), and exploring biological strategies targeting healing pathways (e.g., PI3K/AKT and Wnt/β-catenin) are avenues for achieving a reliable and efficient biological fusion within the UBE setting. Concurrently, integrating cutting-edge ancillary technologies such as computer navigation, robotics, and augmented reality will further enhance the precision and safety of UBE fusion, potentially shortening the learning curve for surgeons.

However, the widespread adoption of advanced biomaterials and technologies into routine UBE fusion also faces practical hurdles. Factors such as the comparative cost-effectiveness of novel biomaterials, the additional learning curve associated with new devices within the UBE setting, and potential regulatory challenges for newer biologics or “intelligent” platforms must be carefully considered and addressed to ensure their accessibility and sustainable implementation. Despite this promising outlook, high-quality long-term clinical evidence, particularly from randomized controlled trials, is urgently needed. Evidence is required to validate these integrated strategies, define optimal indications, and comprehensively evaluate the value and cost-effectiveness of UBE fusion, especially in complex cases (e.g., multilevel procedures, revisions, osteoporosis).

UBE fusion can reach its full potential to offer a superior treatment through continuously innovating techniques, rigorously validating clinical outcomes, addressing practical implementation challenges, and applying a deep understanding of bone healing biology.