Biocompatible Nanocomposites for Postoperative Adhesion: A State-of-the-Art Review

Abstract

To reduce and prevent postsurgical adhesions, a variety of scientific approaches have been suggested and applied. This includes the use of advanced therapies like tissue-engineered (TE) biomaterials and scaffolds. Currently, biocompatible antiadhesive constructs play a pivotal role in managing postoperative adhesions and several biopolymer-based products, namely hyaluronic acid (HA) and polyethylene glycol (PEG), are available on the market in different forms (e.g., sprays, hydrogels). TE polymeric constructs are usually associated with critical limitations like poor biocompatibility and mechanical properties. Hence, biocompatible nanocomposites have emerged as an advanced therapy for postoperative adhesion treatment, with hydrogels and electrospun nanofibers among the most utilized antiadhesive nanocomposites for in vitro and in vivo experiments. Recent studies have revealed that nanocomposites can be engineered to generate smart three-dimensional (3D) scaffolds that can respond to different stimuli, such as pH changes. Additionally, nanocomposites can act as multifunctional materials for the prevention of adhesions and bacterial infections, as well as tissue healing acceleration. Still, more research is needed to reveal the clinical potential of nanocomposite constructs and the possible success of nanocomposite-based products in the biomedical market.

Keywords: antiadhesive agents; biocompatible nanocomposites; biopolymers; drug delivery; postoperative adhesion; tissue engineering; tissue healing.

Figure 1

Schematic illustration of different types of tissue adhesion, including tendon adhesion (a–c), pericardial adhesion (d–f), abdominal adhesion (g,h), epidural adhesion (i,j), and intrauterine adhesion (k–n). Reproduced with permission from [21].

Figure 2

A schematic representation of the role of fibrin and fibroblasts in the formation and inhibition of tissue adhesion. Reproduced with permission from [47].

Figure 3

Classification of nanocomposites based on constituent matrix (polymer, ceramic, or metal) and incorporated phases.

Figure 4

Antiadhesive and anti-cancer properties of COL-APG_Cys@HHD hydrogel. (A) (a) Optical image of the hemolysis interaction between blood and five distinct groups, namely, Col-APG-Cys@HHD, Col-APG-Cys, Col-APG, PBS, and water. (b) Quantitative representation of the hemolysis ratio of relevant samples. (c) Macroscopic observation of the control group and the antiadhesive effect of medical glue, Col-APG, Col-APG-Cys, and Col-APG-Cys@HHD hydrogels on tissue. (d) Distribution of adhesion scores on days 7 and 14 after surgery in the corresponding groups. (e) Histopathological evaluation of normal organ sections collected from animals treated with saline, medical glue, Col-APG, Col-APG-Cys, and Col-APG-Cys@HHD hydrogels after sacrifice through H&E staining. The scale bar shows 100 µm. (B). (a) Variations in body weight of tumor-bearing mice for the duration of therapy. Data are shown as mean ± SD, n = 5. (b) Tumor growth curves after tail IV injection of saline and Col-APG-Cys@HHD. Data are shown as mean ± SD, n = 5. (**** p < 0.0001) (c) Macroscopic images of the tumor size stripped from mice in control and Col-APG-Cys@HHD groups. (d) H&E staining of normal organs and tumor sections collected from animals treated with saline and Col-APG-Cys@HHD at the end of the experiment. The scale bar shows 100 µm. Reproduced with permission from [23].

Figure 5

Photo-crosslinkable nanopatch (pCNP) prevents postoperative peritoneal adhesion in a parietal peritoneal excision (PPE) model in rats. (a) Macroscopic images representing PPE and the administration of pCNP. (b) Representative images of postsurgical adhesions in rats after 14 days of treatment with PBS (the injured site was incubated with saline followed by UV irradiation); A only (the injured site was incubated with NP-A followed by saline under UV irradiation); A + A (the injured site was incubated with NP-A followed by NP-A again under UV irradiation); A′ + B (the injured site was incubated with NP-A′ (NP-A without targeting ligand) followed by NP-B under UV irradiation); pCNP w/o Dex (the injured site was incubated with NP-A without dexamethasone 21-palmitate followed by NP-B under UV irradiation); Seprafilm^® (the injured site was incubated with saline under UV irradiation, the saline was wiped out, and the injured site was covered with Seprafilm^®); and pCNP (the injured area was incubated with NP-A followed by NP-B under UV irradiation). (All the incubation and irradiation times were 10 min.) (c–j) H&E staining photographs representing the thickness of adhesion/fibrosis in untreated animals (c) and rats that underwent surgery and were further treated with PBS (d), NP-A only (e), NP-A + NP-A (f), NP-A′ + NP-B (g), pCNP without dexamethasone 21-palmitate (h), Seprafilm^® (i), and pCNP (j). The scale bar shows 2 mm. (k,l) Qualitative (k) and quantitative (l) scoring analysis of postoperative adhesions in rats 14 days after treatment. Data presented as scatter dot plot with median line (for A + A, n = 6; for pCNP w/o Dex, n = 7; for Seprafilm^®, n = 8; for other groups, n = 9). (m) Quantitative evaluation of the adhesion/fibrosis thickness in (d–j). Data are shown as mean ± standard error of the mean (SEM), n = 3. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001. Reproduced with permission from [143].