Engineering of Bioresorbable Polymers for Tissue Engineering and Drug Delivery Applications

Abstract

Herein, the recent advances in the development of resorbable polymeric-based biomaterials, their geometrical forms, resorption mechanisms, and their capabilities in various biomedical applications are critically reviewed. A comprehensive discussion of the engineering approaches for the fabrication of polymeric resorbable scaffolds for tissue engineering, drug delivery, surgical, cardiological, aesthetical, dental and cardiovascular applications, are also explained. Furthermore, to understand the internal structures of resorbable scaffolds, representative studies of their evaluation by medical imaging techniques, e.g., cardiac computer tomography, are succinctly highlighted. This approach provides crucial clinical insights which help to improve the materials' suitable and viable characteristics for them to meet the highly restrictive medical requirements. Finally, the aspects of the legal regulations and the associated challenges in translating research into desirable clinical and marketable materials of polymeric-based formulations, are presented.

Keywords: clinical challenges; drug delivery; implants; medical imaging; polymer matrices; resorbable biomaterials; tissue engineering.

Figure 1

Schematic summary of the mechanisms of structural changes that occur in polymer‐glass composites during degradation, over different timescales, and for different filler loadings. Reproduced with permission.^{[ 73 ]}

Figure 2

Illustrations of common fabrication techniques for bioresorbable polymers and composites. Melt processing: A) injection molding or micro‐injection molding, B) melt compounding (twin‐screw extrusion); Solvent processing: C) freeze drying, D) electrospinning; and Additive manufacturing: E) materials extrusion or direct ink writing, F) vat photopolymerization, and G) powder bed methods like powder bed fusion or binder jetting. Reproduced with permission^{[ 95} , ⁹⁶ , ⁹⁷ , ⁹⁸ , ⁹⁹ , ^{100 ]} and under CC BY‐NC‐ND 4.0.^{[ 101 ]}

Figure 3

A) (i) SEM images of the scaffolds produced by using the VPP, showing the neat polymer (with smooth surface), and composites with β‐TCP (with microscale surface roughness). (ii) Example of the route to produce a porous and personalized composite implant for a large mandibular defect. Reproduced with permission.^{[ 131 ]} B) Example of a fully resorbable cranial implant manufactured by the PBF technique from a composite of PLA and calcium carbonate. Reproduced with permission^{[ 132 ]} under the CC‐BY 4.0 license. C) A magnetically assisted orientation of fibers in a composite produced by the DIW technique, showing cell orientations on the composites with: random (i) and aligned (ii) fibers. Scale bar = 250 µm. Reproduced with permission.^[133.]

Figure 4

RapidSorb fixation system for maxillofacial procedures: A) plate, B) screw, C) mesh/foil, D) adjustment of implant size during operation, E) water bath, and F) adjustment of implant shape during operation. Reprinted from [178116.pdf (llnwd.net)].

Figure 5

Personalized maxillofacial osteosynthesis system: A) computed tomography image of a frontal lobe defect temporarily filled with neurosurgical cement, B) reconstruction of the patient's skull and the creation of a three‐dimensional implant model fitted to the defective bone, C) 3D‐printed implant manufactured of poly(l‐lactide‐co‐d,l‐lactide) and nanohydroxyapatite formulation, and D) surgical procedure of a scaffold implantation in the patient's skull. Reprinted from [www.cyberbone.eu].

Figure 6

A) Schematic illustration of the synthesis of heparin‐conjugated gelatin nanospheres and the hierarchical VEGF‐loaded nanofibrous microspheres and B) H&E stained images of regenerated pulp‐like tissues in the full‐length root canal after in vivo implantation for nine weeks. Adapted from.^{[ 247 ]} Copyright 2016 Elsevier Ltd.

Figure 7

Nanofibrous tubular matrices‐guided tubular dentin regeneration. A) A confocal image showing a DPSC extending its process into a tubule, B) Confocal image after the DPSC/tubular matrix construct was cultured in vitro for seven days, C) Trichrome staining after the DPSC/tubular matrix construct was cultured in vitro for two weeks and D) Tubular dentin regeneration after implantation for four weeks. Adapted from ref.[252] Copyright 2017 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

Figure 8

Applications of bioresorbable composites: A) OSTEOTRANS MX® implants for cranial, oral, and maxillofacial use. Reproduced from ref.[303] under the CC‐BY 4.0 license, B) OSTEOTRANS MX® implants used for facial fractures, immediately postoperative (left) and 2 years postoperative (right), showing implant resorption and some excess frontal bone growth. Reproduced with permission from ref. [300] C) Biosteon HA/PLLA interference screw 12 months post‐implantation, showing a new bone growth in a sheep model. Reproduced with permission from^{[ 304 ]} and D) Glass fiber reinforced collagen scaffolds for muscle tissue engineering, showing cell orientation (red arrow) along glass fibers. Reproduced with permission from ref.[305]

Figure 9

Follow‐up evaluation with CTA of Absorb BVS treatment of a spontaneous coronary dissection. Intracoronary hematoma was observed in the left circumflex coronary artery (Panel A, arrow) and treated with a BRS thereby, achieving a complete recovery of the coronary lumen (Panel B, arrow). CTA could correctly locate the previously implanted stents through the marker identification (Panel C, arrowheads) and confirm good result persistence.

Figure 10

Coronary wall evaluation of a Magmaris bioresorbable scaffold that was implanted in a left circumflex with mixed plaque. Curved multiplanar reconstruction (Panel A) allows stent identification through radiopaque markers and plaque visualization, Plaque analysis tools identify the vessel wall composition at cross‐section (Panel B) and along the vessel (Panel C).

Figure 11

Schematic representation of the different approaches that are being exploited for controlled drug delivery in different bone applications and a brief regulatory pathway for approval toward clinics.

Figure 12

Scholarly research outputs in the last 5 years, in “Bone Drug Delivery” domain in the fields of cancer therapy, infection management, osseointegration and bone in vitro models. Data extracted from Web of Science (accessed August 2^nd, 2024, research articles excluding review articles and book chapters).