Vital pulp therapy (VPT) represents a more conservative approach in preserving teeth that are compromised by dental caries, traumatic injury or restorative procedures. Unlike root canal treatment that completely removes dental pulp tissues [1], VPT protects and heals a compromised pulp using less invasive techniques such as direct or indirect pulp capping, partial pulpotomy, or complete pulpotomy [2,3]. These techniques represent proactive measures in the continuum of dental care. They seek to prevent tooth loss by intervening before the situation necessitates comprehensive root canal therapy.

Vital pulp therapy was originally used for treating primary teeth and immature permanent teeth. However, there has been a notable paradigm shift in recent years in using these procedures for managing mature permanent teeth. This paradigm shift is marked by a transition from experience-led clinical practice to more biology-supported treatment strategies, as well as the introduction of hydraulic calcium silicate materials for treating exposed pulps [2], [3], [4], [5]. This evolution extends the objectives of VPT from simply promoting root development in immature teeth, to immunomodulation of pulpal inflammation in mature teeth. Contemporary VPT strategies are capable of rejuvenating pulp tissues previously considered only suitable for root canal therapy due to irreversible inflammation. Clinical studies have demonstrated the potential for VPT to successfully preserve pulp vitality in mature permanent teeth that are affected by irreversible pulpitis, with promising survival rates. A recent systematic review and meta-analysis highlighted the efficacy of pulpotomy in offering comparable short-term (1 year) and medium-term (5 years) clinical outcomes to root canal treatment in managing non-traumatic pulpitis associated with spontaneous pain [6].

A recent study comparing direct pulp capping using saline vs 2.5 % sodium hypochlorite (NaOCl) for arrest of hemorrhage in adult teeth found high success rate with NaOCl (89 %) at one year [7]. However, the success rate declined to 55 % at four years [8]. This raises concerns about the lack of reliable objective diagnostic tests for pulpal inflammation to ensure the long-term success of VPT [2,9]. Currently, direct observation of the pulp with a surgical microscope is recommended for evaluating inflammation, and for identifying the amount of the pulp tissue to be removed [2,3]. Despite its convenience, direct visualization of the pulp condition is subjective. The accuracy in predicting potential VPT outcome prior to treatment also needs to be improved.

Contemporary views on pulpitis are moving away from the binary classification as reversible pulpitis or irreversible pulpitis. Pulpal inflammation is more and more perceived as a condition that varies in severity [4,5,10,11]. This change is backed up by histological findings showing there is no clear line that marks an inflamed pulp as beyond repair [4,10,11]. Traditionally, VPT procedures focus on excising inflamed/infected pulp tissue and sealing the partially excised pulp with hydraulic calcium silicate cements. Nevertheless, the use of these procedures alone may not adequately resolve inflammation for effective pulp healing [4,10]. Bioactive agents such as resolvin E1, epigallocatechin-3-gallate, or simvastatin have been used as adjuncts in VPT for immunomodulation, and augmentation of osteogenesis [12], [13], [14], [15]. Without a clinical test to diagnose and measure pulpal inflammation, it is challenging to determine the optimal condition for applying these bioactive agents.

Hydrogels that respond to matrix metalloproteinases (MMPs) offer a new way to treat periodontal infections. These stimuli-responsive hydrogels may be loaded with bioactive agents that are released upon degradation of the hydrogel [16,17]. This method of controlled release enables the maximum efficacy to be achieved while reducing adverse side effects. Research indicates that MMP-9 is responsible for tissue degradation in inflamed dental pulps [18], [19], [20], [21], [22], [23]. The level of MMP-9 in dentinal fluid or pulpal blood has been shown to correlate with the severity of pulpitis. Hence, MMP-9 may be used as a biomarker of pulpal tissue degradation, for diagnosing or monitoring the progress or resolution of pulpitis [3,24]. This should help in the development of environmentally sensitive delivery systems for bioactive agents in VPT.

The innate defense regulator peptide IDR-1002 possesses significant immunomodulatory and anti-inflammatory activities [25,26]. The development of this synthetic molecule is inspired by naturally occurring cationic peptides. When used in combination with ciprofloxacin for pulpal revascularization, IDR-1002 demonstrates antimicrobial and immunomodulatory properties in vitro [27]. Nanofibers embedding ciprofloxacin and IDR-1002 support the adherence of stem cells derived from the apical papilla. This combination also facilitates the growth of pulp-like tissue with minimal inflammatory responses [28]. These favorable properties render IDR-1002 a promising candidate for addressing pulp inflammation.

Accordingly, the objectives of the present study were to design and evaluate an MMP-9-responsive hydrogel for resolving pulp inflammation in VPT. The null hypotheses tested were: 1) activated MMP-9 has no effect on the degradation behavior of the hydrogel; 2) Release of IDR-1002 from the MMP-9-responsive hydrogel produces no antibacterial effect against multispecies oral biofilms.