Bioengineered Materials for Skull Base Reconstruction—Current Clinical Applications: Systematic Review and Meta-analysis

Abstract

Introduction

Skull base reconstruction (SBR) is a crucial aspect of open and endoscopic skull base surgery. Currently, multilayer reconstruction with vascularized tissues is the standard technique. Despite advancements, complications such as postoperative cerebrospinal fluid leaks (PO-CSF-L) and infections persist. Bioengineered materials (BEM) have emerged for SBR, showing promising results.

Methods

A systematic review was conducted using Embase, PubMed, Scopus, and Cochrane databases. We performed a proportional meta-analysis of studies utilizing BEM for SBR and a comparative analysis with control groups that underwent SBR without biomaterials. The odds ratio assessed treatment effects for binary outcomes.

Results

From 1,075 potential articles, 14 met the inclusion criteria. Five BEM were identified: hydroxyapatite (HXA), leukocyte–platelet-rich fibrin (L-PFR), collagen matrix (CM), polyglycolic acid (PGA), and porous polyethylene (PP). The analysis included 1,960 patients, with 1,570 in experimental groups using BEM. Pooled data indicated a PO-CSF-L proportion of 0.02% (95% CI: 0.01–0.03%), postoperative CSF diversion (PO-CSF-d) at 0.01% (95% CI: 0.00–0.04), and PO infection at 0.02% (95% CI: 0.00–0.05%). Common effect models showed that CM had a lower total PO infection rate (0.01; 95% CI: 0.00–0.01, p = 0.0006) compared with HXA (0.08; 95% CI: 0.05–0.11, p = 0.0007). Comparative analysis demonstrated lower odds of PO-CSF-L (OR 0.37; 95% CI: 0.15–0.89, p = 0.026) and infections (OR 0.47; 95% CI: 0.13–1.47, p = 0.264) in patients with BEM.

Conclusion

Our results indicate that bioengineered materials are viable for skull base reconstruction, associated with low rates of postoperative CSF leaks, diversions, and infections.

Keywords

bioengineered materials - skull base reconstruction - CSF leak - infection - meta-analysis

Publikationsverlauf

Eingereicht: 06. Mai 2025

Angenommen: 31. August 2025

Accepted Manuscript online:
01. September 2025

Artikel online veröffentlicht:
11. September 2025

• References

• 1 Kuriakose MA, Trivedi NP, Kekatpure V. Anterior skull base surgery. Indian J Surg Oncol 2010; 1 (02) 133-145
• 2 Verillaud B, Bresson D, Sauvaget E. et al. Endoscopic endonasal skull base surgery. Eur Ann Otorhinolaryngol Head Neck Dis 2012; 129 (04) 190-196
• 3 Fischbein NJ, Kaplan MJ. Magnetic resonance imaging of the central skull base. Top Magn Reson Imaging 1999; 10 (05) 325-346
• 4 Nonaka Y, Fukushima T, Hayashi N, Sorimachi T, Matsumae M. Dural and skull base reconstruction to eliminate postoperative complications related to cerebrospinal fluid leakage: technical nuances and surgical outcome. Res Square. 2021; . Epub ahead of print.
• 5 Khan DZ, Ali AMS, Koh CH. et al. Skull base repair following endonasal pituitary and skull base tumour resection: a systematic review. Pituitary 2021; 24 (05) 698-713
• 6 Stapleton AL, Tyler-Kabara EC, Gardner PA, Snyderman CH. The costs of skull base surgery in the pediatric population. J Neurol Surg B Skull Base 2015; 76 (01) 39-42
• 7 Karsy M, Jensen MR, Guan J, Ravindra VM, Bisson EF, Couldwell WT. EQ-5D quality-of-life analysis and cost-effectiveness after skull base meningioma resection. Neurosurgery 2019; 85 (03) E543-E552
• 8 Jung H, Shah A, Ajlan A. Perioperative cerebrospinal fluid diversion utilizing lumbar drains in transsphenoidal surgery. J Neurol Disord 2014; 02 (02) 150
• 9 Bakhshi SK, Suhail N, Mitha R, Moazzam M, Zahid N, Shamim MS. Lumbar drain for temporary cerebrospinal fluid diversion: factors related to the risks of complications at a university hospital. World Neurosurg 2020; 143: e193-e198
• 10 Samadani U, Huang JH, Baranov D, Zager EL, Grady MS. Intracranial hypotension after intraoperative lumbar cerebrospinal fluid drainage. Neurosurgery 2003; 52 (01) 148-151 , discussion 151–152
• 11 Nelson RF, Roche JP, Gantz BJ, Hansen MR. Middle cranial fossa (MCF) approach without the use of lumbar drain for the management of spontaneous cerebral spinal fluid (CSF) leaks. Otol Neurotol 2016; 37 (10) 1625-1629
• 12 Potter NJ, Graham SM, Chang EH, Greenlee JDW. Bioabsorbable plate cranial base reconstruction. Laryngoscope 2015; 125 (06) 1313-1315
• 13 Snyderman CH, Kassam AB, Carrau R, Mintz A. Endoscopic reconstruction of cranial base defects following endonasal skull base surgery. Skull Base 2007; 17 (01) 73-78
• 14 Laedrach K, Lukes A, Raveh J. Reconstruction of skull base and fronto-orbital defects following tumor resection. Skull Base 2007; 17 (01) 59-72
• 15 Prickett KK, Wise SK. Grafting materials in skull base reconstruction. Adv Otorhinolaryngol 2013; 74: 24-32
• 16 Lam K, Luong AU, Yao WC, Citardi MJ. Use of autologous fat grafts for the endoscopic reconstruction of skull base defects: indications, outcomes, and complications. Am J Rhinol Allergy 2018; 32 (04) 310-317
• 17 Safavi-Abbasi S, Komune N, Archer JB. et al. Surgical anatomy and utility of pedicled vascularized tissue flaps for multilayered repair of skull base defects. J Neurosurg 2016; 125 (02) 419-430
• 18 Yoshimoto T, Sawamura Y, Houkin K, Abe H. Effectiveness of fibrin glue for preventing postoperative extradural fluid leakage. Neurol Med Chir (Tokyo) 1997; 37 (12) 886-889 , discussion 889–890
• 19 Hadad G, Bassagasteguy L, Carrau RL. et al. A novel reconstructive technique after endoscopic expanded endonasal approaches: vascular pedicle nasoseptal flap. Laryngoscope 2006; 116 (10) 1882-1886
• 20 Rawal RB, Ambrose EC, Patel MR, Zanation AM. Advances in reconstruction of the skull base. Curr Otorhinolaryngol Rep 2013; 1 (04) 191-196
• 21 Champagne P-O, Zenonos GA, Wang EW, Snyderman CH, Gardner PA. The rhinopharyngeal flap for reconstruction of lower clival and craniovertebral junction defects. J Neurosurg 2021; 135 (05) 1319-1327
• 22 Liu JK, Gottfried ON, Cole CD, Dougherty WR, Couldwell WT. Porous polyethylene implant for cranioplasty and skull base reconstruction. Neurosurg Focus 2004; 16 (03) ECP1
• 23 Kwarcinski J, Boughton P, Ruys A, Doolan A, Van Gelder J. Cranioplasty and craniofacial reconstruction: a review of implant material, manufacturing method and infection risk. Appl Sci (Basel) 2017; 7 (03) 276
• 24 Zanotti B, Zingaretti N, Verlicchi A, Robiony M, Alfieri A, Parodi PC. Cranioplasty: review of materials. J Craniofac Surg 2016; 27 (08) 2061-2072
• 25 Page MJ, McKenzie JE, Bossuyt PM. et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021; 372: n71
• 26 Sterne JA, Hernán MA, Reeves BC. et al. ROBINS-I: a tool for assessing risk of bias in non-randomized studies of interventions. BMJ 2016; 355: i4919
• 27 Sterne JAC, Savović J, Page MJ. et al. RoB 2: a revised tool for assessing risk of bias in randomized trials. BMJ 2019; 366: l4898
• 28 Yamaguchi S, Terasaka S, Okamoto M. et al. Simplified dural reconstruction procedure using biocompatible polyglycolic acid felt with autologous abdominal fat grafts after a transpetrosal approach. World Neurosurg 2019; 132: e710-e715
• 29 Esposito F, Dusick JR, Fatemi N, Kelly DF. Early surgical complications after endoscopic expanded endonasal approaches to the skull base. J Neurosurg 2011; 114 (05) 1258-1265
• 30 Lee SH, Ha CM, Hong SD. et al. Clinical impact of hydroxyapatite on the outcome of skull base reconstruction for intraoperative high-flow CSF leak: a propensity score matching analysis. Front Oncol 2022; 12: 906162
• 31 Shahein M, Montaser AS, Barbero JMR. et al. Collagen matrix with mucoperiosteum graft as an effective fatless flapless reconstruction after endoscopic pituitary adenoma resection. Oper Neurosurg (Hagerstown) 2020; 19 (06) E573-E580
• 32 Hong I, Kim KH, Seo Y, Choo YH, Lee HJ, Kim SH. Efficacy of hydroxyapatite-based skull base reconstruction for intraoperative high-flow cerebrospinal fluid leakage performed by less-experienced surgeons. Sci Rep 2023; 13 (01) 14886
• 33 Desai R, Kapur Z, Hammond B. et al. Safety and efficacy of hydroset cranioplasty as an adjunct to gasket-seal and nasoseptal flap closure of the skull base: a case-controlled study. Acta Neurochir (Wien) 2024; 166 (01) 256
• 34 Younus I, Gerges MM, Uribe-Cardenas R. et al. How long is the tail end of the learning curve? Results from 1000 consecutive endoscopic endonasal skull base cases following the initial 200 cases. J Neurosurg 2020; 134 (03) 750-760
• 35 Xue H, Wang X, Yang Z, Bi Z, Liu P. Risk factors and outcomes of cerebrospinal fluid leak related to endoscopic pituitary adenoma surgery. Br J Neurosurg 2020; 34 (04) 447-452
• 36 Asemota AO, Ishii M, Brem H, Gallia GL. Comparison of complications, trends, and costs in endoscopic vs microscopic pituitary surgery: analysis from a US health claims database. Neurosurgery 2017; 81 (03) 458-472
• 37 Coucke B, Van Gerven L, De Vleeschouwer S, Van Calenbergh F, van Loon J, Theys T. The incidence of postoperative cerebrospinal fluid leakage after elective cranial surgery: a systematic review. Neurosurg Rev 2022; 45 (03) 1827-1845
• 38 Huo CW, King J, Goldschlager T. et al. The effects of cerebrospinal fluid (CSF) diversion on post-operative CSF leak following extended endoscopic anterior skull base surgery. J Clin Neurosci 2022; 98: 194-202
• 39 Caggiano C, Penn DL, Laws Jr ER. The role of the lumbar drain in endoscopic endonasal skull base surgery: a retrospective analysis of 811 cases. World Neurosurg 2018; 117: e575-e579
• 40 Zwagerman NT, Wang EW, Shin SS. et al. Does lumbar drainage reduce postoperative cerebrospinal fluid leak after endoscopic endonasal skull base surgery? A prospective, randomized controlled trial. J Neurosurg 2018; 131 (04) 1172-1178
• 41 Guo X, Zhu Y, Hong Y. Efficacy and safety of intraoperative lumbar drain in endoscopic skull base tumor resection: a meta-analysis. Front Oncol 2020; 10: 606
• 42 Lai LT, Trooboff S, Morgan MK, Harvey RJ. The risk of meningitis following expanded endoscopic endonasal skull base surgery: a systematic review. J Neurol Surg B Skull Base 2014; 75 (01) 18-26
• 43 Kono Y, Prevedello DM, Snyderman CH. et al. One thousand endoscopic skull base surgical procedures demystifying the infection potential: incidence and description of postoperative meningitis and brain abscesses. Infect Control Hosp Epidemiol 2011; 32 (01) 77-83
• 44 Milanese L, Zoli M, Sollini G. et al. Antibiotic prophylaxis in endoscopic endonasal pituitary and skull base surgery. World Neurosurg 2017; 106: 912-918
• 45 Kim Y-H, Kang H, Dho Y-S, Hwang K, Joo J-D, Kim YH. Multi-layer onlay graft using hydroxyapatite cement placement without cerebrospinal fluid diversion for endoscopic skull base reconstruction. J Korean Neurosurg Soc 2021; 64 (04) 619-630
• 46 Matic D, Phillips JH. A contraindication for the use of hydroxyapatite cement in the pediatric population. Plast Reconstr Surg 2002; 110 (01) 1-5
• 47 Allen KP, Isaacson B, Kutz JW, Purcell PL, Roland PS. The association of meningitis with postoperative cerebrospinal fluid fistula. J Neurol Surg B Skull Base 2012; 73 (06) 401-404
• 48 Kang Y-H, Jeon SH, Park JY. et al. Platelet-rich fibrin is a Bioscaffold and reservoir of growth factors for tissue regeneration. Tissue Eng Part A 2011; 17 (3-4): 349-359
• 49 Li Q, Geng Y, Lu L, Yang T, Zhang M, Zhou Y. Platelet-rich fibrin-induced bone marrow mesenchymal stem cell differentiation into osteoblast-like cells and neural cells. Neural Regen Res 2011; 6 (31) 2419-2423
• 50 Kumar N, Prasad K, Ramanujam L, K R, Dexith J, Chauhan A. Evaluation of treatment outcome after impacted mandibular third molar surgery with the use of autologous platelet-rich fibrin: a randomized controlled clinical study. J Oral Maxillofac Surg 2015; 73 (06) 1042-1049
• 51 Chignon-Sicard B, Georgiou CA, Fontas E. et al. Efficacy of leukocyte- and platelet-rich fibrin in wound healing: a randomized controlled clinical trial. Plast Reconstr Surg 2012; 130 (06) 819e-829e
• 52 Fredes F, Pinto J, Pinto N. et al. Potential effect of leukocyte-platelet-rich fibrin in bone healing of skull base: a pilot study. Int J Otolaryngol 2017; 2017: 1231870
• 53 Soldatova L, Campbell RG, Elkhatib AH. et al. Role of leukocyte-platelet-rich fibrin in endoscopic endonasal skull base surgery defect reconstruction. J Neurol Surg B Skull Base 2017; 78 (01) 59-62
• 54 Ibrahim AA, Yoneis A, Elsakka A, Elwany S. Fat enhanced leukocyte-platelet-rich fibrin versus fascia lata in endoscopic reconstruction of CSF leaks. Eur Arch Otorhinolaryngol 2023; 280 (09) 4141-4147
• 55 Taufique ZM, Bhatt N, Zagzag D, Lebowitz RA, Lieberman SM. Revascularization of AlloDerm used during endoscopic skull base surgery. J Neurol Surg B Skull Base 2018; 80 (01) 46-50
• 56 Disa JJ, Klein MH, Goldberg NH. Advantages of autologous fascia versus synthetic patch abdominal reconstruction in experimental animal defects. Plast Reconstr Surg 1996; 97 (04) 801-806
• 57 Disa JJ, Goldberg NH, Carlton JM, Robertson BC, Slezak S. Restoring abdominal wall integrity in contaminated tissue-deficient wounds using autologous fascia grafts. Plast Reconstr Surg 1998; 101 (04) 979-986
• 58 Dehdashti AR, Ganna A, Karabatsou K, Gentili F. Pure endoscopic endonasal approach for pituitary adenomas: early surgical results in 200 patients and comparison with previous microsurgical series. Neurosurgery 2008; 62 (05) 1006-1015 , discussion 1015–1017
• 59 Han Z-L, He D-S, Mao Z-G, Wang H-J. Cerebrospinal fluid rhinorrhea following trans-sphenoidal pituitary macroadenoma surgery: experience from 592 patients. Clin Neurol Neurosurg 2008; 110 (06) 570-579
• 60 Penn DL, Burke WT, Laws ER. Management of non-functioning pituitary adenomas: surgery. Pituitary 2018; 21 (02) 145-153
• 61 Oakley GM, Christensen JM, Winder M. et al. Collagen matrix as an inlay in endoscopic skull base reconstruction. J Laryngol Rhinol Otol 2018; 132 (03) 214-223
• 62 Tanji M, Oishi M, Sano N. et al. Impact of collagen matrix on reconstructive material selection and postoperative complications in endoscopic endonasal skull base surgery. J Neurosurg 2024; 141 (01) 204-211
• 63 Terasaka S, Iwasaki Y, Shinya N, Uchida T. Fibrin glue and polyglycolic acid nonwoven fabric as a biocompatible dural substitute. Neurosurgery 2006; 58 (01) ONS134-ONS139 , discussion ONS134–ONS139
• 64 Terasaka S, Taoka T, Kuroda S. et al. Efficacy and safety of non-suture dural closure using a novel dural substitute consisting of polyglycolic acid felt and fibrin glue to prevent cerebrospinal fluid leakage—a non-controlled, open-label, multicenter clinical trial. J Mater Sci Mater Med 2017; 28 (05) 69
• 65 Klimo Jr P, Browd SR, Pravdenkova S, Couldwell WT, Walker ML, Al-Mefty O. The posterior petrosal approach: technique and applications in pediatric neurosurgery. J Neurosurg Pediatr 2009; 4 (04) 353-362
• 66 Kusumi M, Fukushima T, Aliabadi H. et al. Microplate-bridge technique for watertight dural closures in the combined petrosal approach. Neurosurgery 2012; 70 (2, Suppl Operative): 264-269
• 67 Uraguchi K, Kozakura K, Makihara S, Fukuda M, Doi A, Ohta T. Two cases of skull base dural reconstruction with a polyglycolic acid felt (Dura wave®). Nippon Jibiinkoka Gakkai Kaiho 2019; 123 (03) 257-263
• 68 Liew S-L, Lo BP, Donnelly MR. et al. A large, curated, open-source stroke neuroimaging dataset to improve lesion segmentation algorithms. Sci Data 2022; 9 (01) 320
• 69 Mracek J, Seidl M, Dostal J. et al. Three-dimensional personalized porous polyethylen cranioplasty in patients at increased risk of surgical site infection. Acta Neurochir (Wien) 2024; 166 (01) 383
• 70 Chung S-B, Nam D-H, Park K, Kim JH, Kong D-S. Injectable hydroxyapatite cement patch as an on-lay graft for the sellar reconstructions following endoscopic endonasal approach. Acta Neurochir (Wien) 2012; 154 (04) 659-664